Clinical trial NCT03496571
Conditions: Eosinophilic Gastritis Eosinophilic Gastroenteritis
Keywords: Eosinophilic Gastritis Eosinophilic Gastroenteritis Eosinophil EG EGE Eosinophilic gastrointestinal disorders EGID
Sponsor: Allakos Inc.
Start date: 2018-07-18; Completion date: 2019-06-24
Enrollment: 65 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2, double-blind, randomized, placebo-controlled study to assess the effects of AK002, given monthly for 4 doses. It is hypothesized that AK002 is more effective than placebo control (alternative hypothesis) in reducing the number of eosinophils per high power field (HPF) in gastric and/or duodenal biopsies before and after receiving AK002 or placebo versus no difference between AK002 and placebo control (null hypothesis).

Detailed description:

Arms: arm 1: Subjects in this arm will receive 4 monthly doses of placebo. arm 2: Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 1 mg/kg, and a fourth dose of 1 mg/kg arm 3: Subjects in this arm will receive 4 monthly doses of AK002: a first dose of 0.3 mg/kg, a second dose of 1 mg/kg, a third dose of 3 mg/kg, and a fourth dose of 3 mg/kg
Interventions: intervention 1: AK002 intervention 2: Placebo
Intervention descriptions: intervention 1: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs). intervention 2: Placebo

Protocol documents:
Prot_000.pdf: 
A P hase 2, M ultice nter, Ra n d o mize d, D o u ble -Bli n d, Place b o -C o ntr olle d St u d y t o E val uate t he 
Efficac y, Safet y, Tolera bilit y, a n d P har mac o d y na mic Effect of A K 0 0 2 i n Patie nts wit h 
E osi n o p hilic Gastritis a n d/ or E osi n o p hilic Gastr oe nteritis  
N C T N u m ber:  N C T 0 3 4 9 6 5 7 1  
D oc u me nt Date:  0 7 Fe br uar y 2 0 1 9  
I R B A p pr o val Date: 2 5 Fe br uar y 2 0 1 9  


 
9 7 5 Isl a n d Driv e, S uit e 2 0 1, R e d w o o d Cit y, C A 9 4 0 6 5  
 
P a ge 1 of 9 8  
Cli ni c al R es e a rc h P r ot o c ol  A K 0 0 2 -0 0 3  
A P h ase 2, M ultice nter, R a n d o mize d, D o u ble -Bli n d, Pl ace b o -C o ntr olle d 
St u d y t o E v al u ate t he Effic ac y, S afet y, T oler a bilit y, a n d 
P h ar m ac o d y n a mic Effect of A K 0 0 2  i n P atie nts wit h 
E osi n o p hilic G astritis  a n d/ or  E osi n o p hilic G astr oe nteritis  
Pr ot oc ol N u m ber 
A K 0 0 2 - 0 0 3 
Versi o n a n d D ate 
Ori gi nal:   
1 1 A u g ust 2 0 1 7 
 
A me n d me nt 1:  
0 2 Marc h 2 0 1 8 
 
A me n d me nt 2:  
1 2 A pril 2 0 1 8 
 
A me n d me nt 3:  
0 7 Ma y 2 0 1 8 
 
A me n d me nt 4:  
2 3 A u g ust 2 0 1 8 
 
A me n d me nt 5. 1:  2 5 Se pte m ber 2 0 1 8 
A me n d me nt 6:   0 7 Fe br u a r y  2 0 1 9 
I n v esti gati o nal Pr o d uct 
A K 0 0 2  
St u d y P has e 
2 
S p o ns or 
Alla k os, I n c.  
9 7 5 Isla n d Dri ve, S uite 2 0 1, Re d w o o d Cit y, C A 9 4 0 6 5 US A  
Me dical M o nit or 
Na me:   
, M D, P h D 
Tele p h o ne: 
 
E- mail:  
  
 
A p pr o v al: 
 
7  F E B 2 0 1 9  
, M D, P h D, 
 
 
Date  
T his c o nfi de ntial 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 x cl usi ve 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 d eral 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 p ers o ns i n v ol ve d i n t he 
st u d y w h o ha v e a n ee d t o k n o w, wit h t he o bli gati o n n ot t o f urt her disse mi nate t his i nf or mati o n.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 of 9 8  
C o nfi de nti al  
I n v esti g at o r P r ot o c ol A g re e m e nt  
I h a ve r ea d t he pr ot oc ol s pecifie d bel o w. I n m y f or mal ca pacit y as Pri n ci pal I n v esti gat or, m y 
d uties i ncl u de e ns uri n g t he safet y of t h e st u d y p atie 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 Alla 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 ne 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 he 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 de ntialit y re q uir e me nt a p plies t o all st u d y staff at t his site. F urt her m ore, o n be half of 
t he st u d y staff a n d m yself, I a gr ee 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 d a nce wit h acce pte d  G o o d Cli nical Practice ( G C P ) pri nci ples a n d t o a bi de b y t he t er ms of 
t his pr ot oc ol. 
Pr ot oc ol N u m ber:  
A K 0 0 2 - 0 0 3 
I N D: 
1 3 5 1 5 8 
Pr ot oc ol Title:  
A P hase 2, M ultice nter, Ra n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle d 
St u d y to E v al uate t he Efficac y, Safet y, T olera bilit y , an d 
P har mac o d y na mic Effect  of A K 0 0 2 i n Patie nts wit h E osi n o p hilic Gastritis  
a n d/ or E osi n o p hilic Gastr oe nteritis  
Ori gi n al Pr ot oc ol:   1 1 A u g ust 2 0 1 7 
A me n d me nt 1:  
0 2 Marc h  2 0 1 8 
A me n d me nt 2:  
1 2 A pril 2 0 1 8 
A me n d me nt 3:  
0 7 Ma y 2 0 1 8 
A me n d me nt 4:  
2 3 A u g ust 2 0 1 8 
A me n d me nt 5 . 1:  
2 5 Se pte m ber 2 0 1 8 
A me n d me nt 6:   
0 7 Fe br u a r y 2 0 1 9 
 
I n vesti g at or: 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
Pri nt e d N a me:    
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
Si g n at ure:   
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
D ate:  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 of 9 8  
C o nfi de nti al  
T a ble of C o nte nts 
Cli nic al Rese arc h Pr ot o c ol A K 0 0 2 - 0 0 3 ........................................................................................ 1 
I n vesti g at or Pr ot o c ol A gree me nt.................................................................................................. 2 
T a ble of C o nte nts ........................................................................................................................... 3 
List of T a bles  .................................................................................................................................. 7 
List of A b bre vi ati o ns ..................................................................................................................... 8 
1.  
Pr ot oc ol S y n o psis ................................................................................................................ 1 0 
2.  
B ac k gr o u n d ......................................................................................................................... 2 2 
2. 1  
Si glec - 8 a n d A K 0 0 2 ................................................................................................... 2 2 
2. 2  
O ver vie w of N o ncli nical St u dies ................................................................................ 2 2 
2. 3  
O ver vie w of Cli nical St u dies  ...................................................................................... 2 3 
2. 4  
E osi n o p hilic Gastr oi ntesti nal Dis or ders  ..................................................................... 2 4 
3.  
R ati o n ale f or St u d y a n d D ose Selecti o n ........................................................................... 2 5 
4.  
St u d y O bjecti ves  ................................................................................................................. 2 6 
4. 1  
Pri mar y O bj ecti ve  ....................................................................................................... 2 6 
4. 2  
Sec o n dar y O bj ecti ves  ................................................................................................. 2 6 
4. 3  
E x pl orat or y O bjecti ves ...............................................................................................2 6  
4. 4  
Safet y O bjecti ves  ........................................................................................................ 2 7 
5.  
St u d y Desi g n  ....................................................................................................................... 2 7 
5. 1  
St u d y O ver vi e w  .......................................................................................................... 2 7 
5. 2  
Sc he d ule of E ve nts ..................................................................................................... 2 8 
6.  
Criteri a f or E v al u ati o n ...................................................................................................... 3 3 
6. 1  
Safet y E n d p oi nts  ......................................................................................................... 3 3 
6. 2  
P har mac o ki netic E n d p oi nts ........................................................................................ 3 3 
6. 3  
Efficac y E n d p oi nts ...................................................................................................... 3 3 
6. 4  
E x pl orat or y E n d p oi nts ................................................................................................3 4  
7.  
P ati e nt Selecti o n  ................................................................................................................. 3 5 
7. 1  
N u m ber of Patie nts ..................................................................................................... 3 5 
7. 2  
St u d y P o p ulati o n ......................................................................................................... 3 5 
7. 3  
I n cl usi o n Criteria ........................................................................................................ 3 5 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 of 9 8  
C o nfi de nti al  
7. 4  
E x cl usi o n Criteria  ....................................................................................................... 3 6 
8.  
Pri o r a n d C o nc urre nt Me dic ati o ns  .................................................................................. 3 7 
8. 1  
Pr o hi bite d Me dicati o ns ...............................................................................................3 8  
8. 2  
All o we d Me dicati o ns .................................................................................................. 3 8 
9.  
St u d y Tre at me nt  ................................................................................................................. 3 8 
9. 1  
F or m ulati o n of Test Pr o d uct a n d Place b o  .................................................................. 3 8 
9. 2  
St u d y Dr u g Pac k a gi n g a n d La b eli n g  .......................................................................... 3 8 
9. 3  
S u p pl y of St u d y Dr u g t o t he I n v esti gati o nal Site ....................................................... 3 9 
9. 4  
St u d y Dr u g D osa ge/ D osa ge Re gi me n ........................................................................ 3 9 
9. 5  
Pre parati o n of St u d y Dr u g .......................................................................................... 3 9 
9. 6  
St u d y Dr u g A d mi nistrati o n ......................................................................................... 3 9 
9. 7  
St u d y Dr u g  St ora ge  ..................................................................................................... 4 0 
9. 8  
St u d y Dr u g A cc o u nta bilit y ......................................................................................... 4 1 
1 0.  
S u bject 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  ...............................4 1  
1 0. 1  S u bject N u m beri n g ..................................................................................................... 4 1 
1 0. 2  Stratificati o n a n d Ra n d o mizati o n  ............................................................................... 4 1 
1 0. 3  Bli n di n g ...................................................................................................................... 4 2 
1 0. 4  Brea ki n g t he Bli n d  ...................................................................................................... 4 3 
1 1.  
St u d y Pr oce d ures a n d G ui deli nes  ..................................................................................... 4 4 
1 1. 1  Dietar y a n d Lif est yl e Restricti o ns  .............................................................................. 4 4 
1 1. 2  P har mac o d y na mic/ Efficac y -R elate d Pr oce d ures  ........................................................ 4 4 
1 1. 2. 1  
P R O Q uesti o n naire ....................................................................................... 4 4 
1 1. 2. 2  
 
1 1. 2. 3  
Es o p ha g o- Gastr o - D u o de n osc o p y wit h Bi o ps y ............................................ 4 5 
1 1. 2. 4  
C o m plete Bl o o d C o u nt wit h Differe ntial ..................................................... 4 6 
1 1. 2. 5  
Baseli ne Diet Assess me nt  ............................................................................ 4 6 
1 1. 2. 6  
 
1 1. 3  Safet y -R elate d Pr o ce d ur es  .......................................................................................... 4 7 
1 1. 3. 1  
C o nc o mita nt Me dicati o ns ............................................................................ 4 7 
1 1. 3. 2  
C o m plete P h ysi cal E x a mi nati o n  .................................................................. 4 7 
1 1. 3. 3  
B o d y Wei g ht a n d Hei g ht .............................................................................. 4 7 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 5 of 9 8  
C o nfi de nti al  
1 1. 3. 4  
St o ol Sa m ple f or O va a n d Parasite  ...............................................................4 8  
1 1. 3. 5  
S y m pt o m- Direct e d P h ysi cal E x a mi nati o n  ................................................... 4 8 
1 1. 3. 6  
Electr ocar di o gra m  ........................................................................................ 4 8 
1 1. 3. 7  
Vital Si g ns  .................................................................................................... 4 8 
1 1. 4  Cli nical La b or at or y Meas ure me nts ............................................................................. 4 8 
1 1. 4. 1  
C o m plete Bl o o d C o u nt wit h Differe ntial ..................................................... 4 9 
1 1. 5  Bl o o d C he mistr y Pr ofile  ............................................................................................. 4 9 
1 1. 5. 1  
Pre g n a nc y T est a n d F olli cle -Sti m ulati n g H or m o ne  ..................................... 4 9 
1 1. 5. 2  
Uri nal ysis  ..................................................................................................... 5 0 
1 1. 5. 3  
Ser ol o g y ....................................................................................................... 5 0 
1 1. 5. 4  
A nti - A K 0 0 2 A nti b o dies ............................................................................... 5 0 
1 1. 5. 5  
Bl o o d f or P har m ac o ki netics a n d St ora ge ..................................................... 5 0 
1 1. 5. 6  
Bl o o d f or E x pl orat or y A nal ysis ................................................................... 5 1 
1 1. 5. 7  
Bl o o d f or E x pl orat or y Safet y A nal ysis, hista mi ne a n d tr y pt ase .................. 5 1  
1 1. 5. 8  
A d diti o nal Sa m ples f or Bi o mar ker S u b- St u d y ............................................. 5 1 
1 2.  
E v al u ati o ns a n d Pr oce d ures b y Visit ................................................................................ 5 1 
1 2. 1  Scree ni n g Peri o d  ......................................................................................................... 5 1 
1 2. 2  Da y 1 – Da y of First I nf usi o n  ..................................................................................... 5 2 
1 2. 3  Da y 4 ( ± 1) ................................................................................................................... 5 4 
1 2. 4  Da y 1 5 ( ± 2) ................................................................................................................. 5 4 
1 2. 5  Da y 2 9 ( ± 3) – D a y of Sec o n d I nf usi o n ....................................................................... 5 4 
1 2. 6  Da y 5 7 ( ± 3) – D a y of T hir d I nf usi o n .......................................................................... 5 6 
1 2. 7  Da y 8 5 ( ± 3) – D a y of F o urt h I nf usi o n  ........................................................................ 5 7 
1 2. 8  Da y 9 9 ( ± 3) ................................................................................................................. 5 8 
1 2. 9  Da y 1 1 3 ( ± 3) ............................................................................................................... 5 8 
1 2. 1 0  Da y 1 4 1 ( ± 3) P ost- Tr eat me nt F oll o w - U p or E arl y Ter mi nati o n * .............................. 5 9 
1 2. 1 1  E xte n de d F oll o w- U p  ................................................................................................... 6 0 
1 3.  
A d verse E ve nt R e p orti n g a n d D oc u me nt ati o n  ................................................................6 0  
1 3. 1  A d verse E v e nts  ........................................................................................................... 6 0 
1 3. 2  Seri o us A d verse E v e nts .............................................................................................. 6 1 
1 3. 3  A d verse E v e nts of S peci al I nt erest  ............................................................................. 6 1 
1 3. 4  I nf usi o n-Relate d Reacti o ns  ......................................................................................... 6 2 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 6 of 9 8  
C o nfi de nti al  
1 3. 5  A na p h yl a xis ................................................................................................................ 6 3 
1 3. 6  E val uati n g A d v erse 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 m e 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 o ce d ure ............................................... 6 5 
1 3. 6. 5  
Acti o n Ta ke n  ................................................................................................6 5  
1 3. 6. 6  
Assess me nt of O ut c o me  ............................................................................... 6 5 
1 3. 7  A d verse E v e nt Re p orti n g Pr oce d ures ......................................................................... 6 5 
1 3. 7. 1  
All A d verse E v e nts  ....................................................................................... 6 5 
1 3. 7. 2  
Seri o us A d v erse E v e nt Re p orti n g  ................................................................6 6  
1 3. 7. 3  
Pre g n a nc y Re p orti n g  .................................................................................... 6 7 
1 3. 7. 4  
A E SI Re p orti n g ............................................................................................ 6 8 
1 3. 8  Me dical M o nit ori n g .................................................................................................... 6 8 
1 3. 9  I n d e pe n de nt Data M o nit ori n g C o m mittee  .................................................................. 6 8 
1 3. 1 0  St u d y Wit h dra w al Criteri a  .......................................................................................... 6 8 
1 3. 1 1  St u d y St o p pi n g R ules ................................................................................................. 6 9 
1 4.  
Disc o nti n u at i o n a n d Re pl ace me nt of P atie nts ................................................................. 6 9 
1 4. 1  Defi niti o n of St u d y C o m pleti o n  ................................................................................. 6 9 
1 4. 2  Earl y Disc o nti n uati o n of St u d y Dr u g ......................................................................... 6 9 
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  Data Sets A nal yz e d  ..................................................................................................... 7 1 
1 5. 3  De m o gra p hic a n d Baseli ne C haracteristics  ................................................................7 1  
1 5. 4  S u bject 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  Efficac y A nal ysis  ........................................................................................................ 7 3 
1 5. 7  S u bject C o nfi de ntialit y  ...............................................................................................7 4  
1 6.  
D at a C ollecti o n, Rete nti o n, a n d M o nit ori n g .................................................................... 7 5 
1 6. 1  Data C ollecti o n I nstr u me nts  ....................................................................................... 7 5 
1 6. 2  Data Ma na ge me nt Pr oce d ures  .................................................................................... 7 5 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 of 9 8  
C o nfi de nti al  
1 6. 3  Data Q u alit y C o ntr ol a n d Re p orti n g ........................................................................... 7 5 
1 6. 4  Data base L oc k/ Discl os ur e of Ra n d o mizati o n C o de ................................................... 7 5 
1 6. 5  Arc hi vi n g of Dat a ....................................................................................................... 7 6 
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 6 
1 6. 7  M o nit ori n g .................................................................................................................. 7 7 
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 7 
1 7. 1  Pr ot oc ol A me n d me nts ................................................................................................7 7  
1 7. 2  I n d e pe n de nt Et hics C o m mittees ................................................................................. 7 7 
1 7. 3  I nf or me d C o nse nt F or m .............................................................................................. 7 8 
1 7. 4  P u blicati o ns ................................................................................................................. 7 8 
1 7. 5  Cli nical Trial Re gistrati o n  .......................................................................................... 7 8 
1 7. 6  Pa y me nt t o S u bjects  .................................................................................................... 7 9 
1 7. 7  I n v esti gat or Res p o nsi bilities ....................................................................................... 7 9 
1 8.  
Ref ere nces  ........................................................................................................................... 8 0 
1 9.  
A p pe n dices  .......................................................................................................................... 8 1 
1 9. 1  A p pe n di x 1: P R O Q uesti o n naire ................................................................................ 8 2 
1 9. 2  A p pe n di x 2: 
 
1 9. 3  A p pe n di x 3: Baseli ne Di et Assess me nt  ...................................................................... 9 1 
1 9. 4  A p pe n di x 4: C o m m o n Ter mi n ol o g y Criteri a f or A d verse E v e nts v. 5. 0 .................... 9 2  
1 9. 5  A p pe n di x 5: E G D Hist ol o g y ...................................................................................... 9 3 
1 9. 6  A p pe n di x 6: Sa m ps o n’s Criteria of A na p h yl a xis ....................................................... 9 5 
1 9. 7  A p pe n di x 7: 
 
1 9. 8  A p pe n di x 8: Bi o mar ker S u b- St u d y f or Selecte d Sites  ............................................... 9 7 
1 9. 9  A p pe n di x 9: A d diti o nal Q uesti o ns f or At o pic C o n diti o ns ......................................... 9 8 
 
List o f T a bles 
Ta ble 1  
Sc he d ule of Assess me nts  ............................................................................................ 2 9 
Ta ble 2  
A d verse E v e nt Se verit y per C T C A E  .......................................................................... 6 4 
Ta ble 3  
A d verse E v e nt Relati o ns hi p t o St u d y Dr u g ................................................................6 4  
Ta ble 4  
A d verse E v e 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 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 8 of 9 8  
C o nfi de nti al  
List of A b bre vi ati o ns 
A C E  
A n gi ote nsi n -c o n verti n g e nz y me  
A D C C  
A nti b o d y -de pe n de nt cell ular c yt ot o xicit y  
A E  
A d verse e ve nt  
A L T  
A la ni ne a mi n otra nsferase 
A N C O V A  
A nal ysis of c o varia nce  
A nti -I L-5  
A nti -i nterle u ki n-5  
A S T  
A s partate a mi n otra nsferase 
A T C  
W orl d Healt h Or ga nizati o n A nat o mical T hera pe utic C he mi cal Classificati o n S yste m  
B MI  
B o d y mass i n de x  
C  
Ce nti gra de  
C B C  
C o m plete bl o o d c o u nt  
C F R  
C o de of Fe deral Re g ulati o n  
c m 
Ce nti meter  
C M H  
C oc hra n -Ma ntel -Hae nszel  
C SI  
C o m p osite sc ore of i nterest  
C T C A E  
C o m m o n T er mi n ol o g y Criteri a f or A d verse E ve nts  
C U  
C hr o nic Urticaria  
E C G  
E lectr ocar di o gra m 
e C R F  
Electr o nic Case Re p ort F or m  
E D C  
Electr o nic Data Ca pt ure (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 M T  
E pit helial mese nc h y mal tra nsiti o n  
E o E  
E osi n o p hilic es o p ha gitis  
E T  
Earl y T er mi nati o n  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F S H  
F ollicle -sti m ulati n g h or m o ne 
G C P  
G o o d Cli nical Practice  
H E E N T  
H E S  
Hea d, e yes, ears, n ose, a n d t hr oat  
H y pere osi n o p hilic S y n dr o me  
HI P A A  
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act  
H P F  
Hi g h p o wer fiel d  
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 H ar m o nisati o n 
i D M C 
I n de pe n de nt Data M o nit ori n g C o m mittee  
I E C 
I n de pe n de nt Et hics C o m mitte e 
I g E 
I m m u n o gl o b uli n E 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 9 of 9 8  
C o nfi de nti al  
I g G 1 
I m m u n o gl o b uli n G 1 
I g G 4 
I m m u n o gl o b uli n G 4 
I N D 
I n vesti gati o nal Ne w Dr u g 
I R B 
I nstit uti o nal Re vie w B oar d 
I R R 
I nf usi o n-Relate d Reacti o n  
I S M 
I n d ole nt s yste mic mast oc yt osis 
I R T 
I nteracti ve Res p o nse T ec h n ol o g y 
I TI M 
I m m u n orece pt or T yr osi ne-bas e d i n hi bit or y m otif 
I U D 
I ntra uteri ne de vice 
I V 
I ntra ve n o us 
k g  
Kil o gra m  
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
m g  
Milli gra m  
MI T T  
M o difie d I nte nti o n -t o-Treat ( p o p ulati o n)  
m M  
Milli m olar  
m L  
Milliliter  
M T D  
Ma xi m u m t olerate d d ose  
Na Cl  
S o di u m c hl ori de  
N K  
Nat ural killer  
P C P  
Pri mar y care p h ysicia n  
P D  
P har mac o d y na mics  
P E  
P h ysical e xa mi nati o n  
PI D  
P atie nt  i de ntificati o n n u mber  
P K  
P har mac o ki netic(s)  
P PI  
Pr ot o n p u m p i n hi bit or  
Q O L  
Q ualit y of life  
S A E  
Seri o us a d verse e ve nt  
S A P  
Statistical A nal ysis Pla n  
 
 
Si glec  
Sialic aci d -bi n di n g, i m m u n o gl o b uli n -li ke lecti n 
S O C  
S yste m or ga n class  
T E A E  
T reat me nt-e mer ge nt a d verse e ve nt  
T E A E SI  
T reat me nt-e mer ge nt a d verse e ve nt of si g nifica nt i nterest  
T N F  
T u m o r necr osis fact or 
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  
V A S  
Vis ual a nal o g scale  
W B C  
W hite bl o o d cell  
W H O D D  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
w/ v  
W ei g ht/ v ol u me  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 0  of 9 8  
C o nfi de nti al  
1.  
Pr ot oc ol S y n o psis 
St u d y Title  
A P hase 2, M ultice nter, Ra n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle d St u d y 
to E val uate t he Efficac y, Safet y, T olera bilit y , a n d P har mac o d y na mic Effect of 
A K 0 0 2 i n Patie nts w it h E osi n o p hilic  Gastritis a n d/ or E osi n o p hilic  
Gastr oe nteritis  
S p o ns or  
Alla k os, I nc., 9 7 5 Isla n d Dri ve, S uite 2 0 1, Re d w o o d Cit y, C A 9 4 0 6 5 U S A  
N u m ber of Sites  
A p pr o xi matel y u p t o 2 5 cli nical ce nters  i n t he U S 
N o ncli nic al 
B ac k gr o u n d  
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 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). 
Si glec -8 has a restricte d tiss ue distri b uti o n, e x presse d selecti vel y o n t he s urface 
of e osi n o p hils, mast cells a n d, at l o wer le vels, o n bas o p hils. Bi n di n g of A K 0 0 2 
to Si glec -8 i n d uces a  si g nal t hat i n hi bits mast cell acti vati o n a n d ca n lea d t o 
a p o pt osis i n e osi n o p hils. I n t he prese nce of effect or cells (s uc h as nat ural killer 
cells), A K 0 0 2 bi n di n g t o Si glec- 8 de pletes circ ulati n g e osi n o p hils b y a nti b o d y-
de pe n de nt cell -me diate d c yt ot o xicit y ( A D C C) . 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  ( E G) a n d/or E osi n o p hilic  Gastr oe nteritis  (E G E ). 
Cli nic al  B ac k gr o u n d Si n gle d oses of 0. 0 0 0 3 – 1 m g/ k g A K 0 0 2 were pre vi o usl y teste d i n healt h y 
v ol u nteers a n d si n gle d oses of 0. 0 0 1 – 1 m g/ k g were pre vi o usl y teste d i n patie nts 
wit h i n d ole nt s yste mic mast oc yt osis (I S M). M ulti ple d oses of 0. 3 m g/ k g ha ve 
bee n gi ve n t o healt h y v ol u nteers, a n d m ulti ple d oses of 1 , 3, 6, a n d 1 0 m g/ k g  
ha ve bee n gi ve n t o I S M patie nts. I n a d diti o n, m ulti ple d oses of 1 m g/ k g  a n d 
3 m g/ k g ha ve bee n gi ve n t o patie nts wit h c hr o nic urticaria ( C U) a n d se vere 
aller gic e ye disease. I n t hese st u dies, A K 0 0 2 p har mac o d y na mic ( P D) acti vit y 
was o bser ve d f or pr ol o n ge d peri o ds of ti me a n d t he A K 0 0 2 p har mac o ki netic 
( P K) para meters de m o nstrate d a half -life a me na ble t o a d mi nistrati o n e ver y 
4 wee ks. I n I S M patie nts, mo nt hl y i n f usi o ns of 1 m g/ k g  a n d 3 m g/ k g ha ve bee n 
a d mi nistere d f or u p t o 6 m o nt hs. Si n gle d oses of 1 m g/ k g  of A K 0 0 2 s u p presse d 
bl o o d e osi n o p hils f or u p t o  8 4 da ys i n healt h y v ol u nteers a n d i n patie nts  wit h 
I S M, C U , a n d se vere aller gic e ye disease . T o date, 5 1 healt h y v ol u nteers 
( 3 6 A K 0 0 2, 1 5 place b o) , 2 5 I S M patie nts, 4 8 C U  patie nts , a n d 3 0  aller gic e ye 
disease patie nts  ha ve bee n e nr olle d i n t o t hese cli nical st u dies.  
I n ge neral, A K 0 0 2 was well t olerate d. I nf usi o n-relate d reacti o ns were o bser ve d 
i n healt h y v ol u nteers, I S M patie nts recei vi ng a first d ose of ≥0. 1 m g/ k g , a n d 
C U a n d aller gic e ye disease patie nts recei vi n g a first d ose of eit her 0. 3 m g/ k g 
or 1 m g/ k g. C o m m o n s y m pt o ms of i nf usi o n- relate d reacti o ns were hea dac he, 
na usea, s weati n g, fl us hi n g a n d re d ness. I nf usi o n- relate d reacti o ns (I R Rs) 
occ urr i 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 al m ost all cases. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 1  of 9 8  
C o nfi de nti al  
Cli nic al B ac k gr o u n d 
c o nt. 
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 Es) o bser ve d were 
hea dac he,  res pirat or y i nfecti o n, na usea, s o m n ole nce, l o wer bac k pai n, s ore 
t hr oat, t hr oat ti g ht ness, nasal c o n gesti o n, a n d li g ht tac h ycar dia. I n all st u dies, 
t here was a tra 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 ociate d wit h a n y a d verse e ve nt, 
a n d a s ustai ne d  s u p pressi o n i n 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 cli nicall y si g nificant c ha n ges i n vital si g ns, 
electr ocar di o gra ms ( E C Gs), cli nical la b orat or y para meters  a n d p h ysical 
e xa mi nati o n were o bser ve d.  
T ar get Dise ase 
B ac k gr o u n d a n d 
R ati o n ale  
E G a n d E G E  re prese nt rare t y pes of e osi n o p hilic gastr oi ntesti nal dis or der s 
( E GI Ds) a n d are c haracterize d b y c hr o nic 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 ( E G) a n d/ or s mall 
i ntesti ne (E G E ) (Pr ussi n , 2 0 1 4; Ree d , 2 0 1 5; Z ha n g, 2 0 1 7 ). Dia g n osis is ma de 
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 he st o mac h a n d 
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. 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 p ossi bl y mast cells , a n d ma y var y de pe n di n g o n t he 
la yer a n d/ or l ocati o n of t he e osi n o p hilic i nfiltrate. S y m pt o ms c o m m o nl y 
i ncl ude na usea, v o miti n g, a b d o mi nal pai n, diarr hea, bl oati n g, earl y satiet y, 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 ; 
Ree d,  2 0 1 5). Je nse n et al. (2 0 1 6 ) esti mate d t he pre vale nce of E G a n d E G E  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 et al. ( 2 0 1 7 ) esti mate t he o verall pre vale nce of EG t o be 5. 1/ 1 0 0, 0 0 0 
pers o ns.  
T here  are n o F D A -a p pr o ve d treat me nts f or E G  a n d/ or E G E . C urre nt t hera pies 
a n d disease ma na ge me nt i ncl u des pr ot o n p u m p i n hi bit ors, restricte d/ele me ntal 
diets, s yste mic or oral c ortic oster oi ds, a n d occasi o na l 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 G E , alt h o u g h partial be nefit ca n be o bser ve d i n patie nts wit h e osi n o p hilic 
es o p ha gitis ( E o E) (Katz , 2 0 1 3). Restricte d/ele me ntal diets are n ot c o nsi dere d 
s ustai na ble f or l o n g-ter m treat me nt a n d are use d m ore s o t o pr o vi de n utriti o n , 
des pite c o nti n ui n g s y m pt o ms . C ortic oster oi ds, s yste mic or oral, ca n pr o vi de 
s y m pt o m relief, b ut are n ot a s ol uti o n f or l o n g -ter m treat me nt d ue t o t heir 
n u mer o us si de effects.  
B 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 re d uci n g t he 
n u m ber a n d/ or acti vati o n of tiss ue mast cells,  A K 0 0 2 ma y be usef ul i n t he 
treat me nt of patie nts wit h E G a n d/or  E G E .  
T he pr o p ose d A K 0 0 2 d oses of 0. 3 m g/ k g a d mi nistere d f or t he first i nf usi o n, 
1 m g/ k g a d mi nistere d f or t he sec o n d i nf usi o n, f oll o we d b y a d ose of eit her  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 2  of 9 8  
C o nfi de nti al  
R ati o n ale f or D ose 
Selecti o n  
1 m g/ k g or 3 m g/ k g a d mi nistere d e ver y 4 wee ks f or 2 s u bse q ue nt i nf usi o ns is 
base d o n  pri or 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,  a n d aller gic e ye disease .
 
 
 
 
 
 
 
 
 
 
 
 
. A starti n g d ose of 0. 3 m g/ k g  wit h a sec o n d d ose of 1 m g/ k g, f oll o we d 
b y a d ose of eit her 1 m g/ k g or 3 m g/ k g f or s u bse q ue nt i nf usi o ns, t heref ore, has 
bee n c h ose n f or t his P hase 2 st u d y wit h A K 0 0 2 i n patie nts wit h E G a n d/ or 
E G E . 
R ati o n ale f or 
N u m ber of S u bjects  
A p pr o xi matel y 6 0 patie nts will be ra n d o mize d 1: 1: 1 t o recei ve 1 of 3 d ose 
re gi me ns i n a d o u ble-bli n d fas hi o n: place b o; a n i nitial 0. 3 m g/ k g A K 0 0 2 d ose, 
f oll o we d b y 3 d oses of 1 m g/ k g A K 0 0 2 gi ve n e ver y 4 wee ks ; or a n i nitial 
0. 3 m g/ k g A K 0 0 2 d ose, a sec o n d d ose of 1 m g/ k g, f oll o we d b y 2 d oses of 
3 m g/ k g A K 0 0 2 gi ve n e ver y 4 wee ks.  
St u d y Desi g n  
T his is a P hase 2, m ultice nter, ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d 
st u d y t o e val uate t he efficac y, safet y, t olera bilit y, a n d p har mac o d y na mic effect 
of A K 0 0 2 i n patie nts wit h E G a n d/ or E G E.  
Scree ni n g data will be re vie we d t o deter mi ne patie nt eli gi bilit y. Patie nts wit h 
E G a n d/ or EG E  w h o meet all i ncl usi o n criteria a n d n o ne of t he e xc l usi o n 
criteria are eli gi ble t o be e nr olle d i nt o t he st u d y. S u bj ects  w h o d o n ot meet all 
eli gi bilit y criteria at scree ni n g, or w h o q ualif y at scree ni n g b ut are n ot e nr olle d, 
ma y be assi g ne d a ne w Patie nt I D n u m ber a n d re-scree ne d o nce. S u bjects re-
scree ne d wit hi n 3 0 da ys of si g ni n g t he i nitial c o nse nt will n ot nee d t o si g n a 
ne w I C F pr o vi d e d t here ha ve bee n n o c ha n ges t o t he I C F. 
T he st u d y is desi g ne d as f oll o ws: 
•  
A 1 4 t o 3 5- da y scree ni n g peri o d wit h baseli ne e val uati o ns f or st u d y 
eli gi bilit y, i ncl u di n g baseli ne acti ve s y m pt o ms of disease ( gat here d b y 
P R O c o m plete d d uri n g scree ni n g) a n d E s o p ha g o- Gastr o- D u o de n osc o p y 
( E G D) wit h bi o ps y. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 3  of 9 8  
C o nfi de nti al  
St u d y Desi g n c o nt.  
•  
If s u bjects meet hist ol o g y a n d s y m pt o m eli gi bilit y criteria, t he y will 
recei ve 4 d oses of A K 0 0 2 or place b o b y I V i nf usi o n o n Da ys 1, 2 9 ( ± 3), 
5 7 ( ± 3), a n d 8 5 ( ± 3). 
•  
A re peat E G D wit h bi o ps y will be perf or me d o n Da y 9 9 ( ± 3) or 
a p pr o xi matel y 2 wee ks after last d ose of st u d y dr u g i f s u bj ect is ter mi nate d 
earl y.  
•  
S u bj ects will be f oll o we d f or 5 6 ( ± 3) da ys after t he last d ose. F oll o w- u p 
visits will occ ur o n Da ys 1 1 3 ( ± 3) a n d 1 4 1 ( ± 3). 
•  
If t he a bs ol ute l y m p h oc yte a n d/ or e osi n o p hil c o u nts ha ve n ot rec o vere d at 
Da y 1 4 1, t he f oll o w- u p peri o d will be e xte n de d, a n d s u bj ects will be 
f oll o we d u ntil t he c o u nts ha ve rec o vere d. D uri n g t he e xte n de d f oll o w- u p 
peri o d, s u bj ects will ret ur n t o t he site e ver y 2 8 da ys ( ± 3) f or a f oll o w- u p 
safet y visit.  
•  
T otal st u d y d urati o n is u p t o a p pr o xi matel y 2 3 – 2 5 wee ks  (st u d y d urati o n 
c o ul d be e xte n de d, as descri be d a b o ve, if t he a bs ol ute l y m p h oc yte a n d / or 
e osi n o p hil c o u nts ha ve n ot rec o vere d). 
Pre -st u d y me dicati o ns a n d pre-e xisti n g dietar y restricti 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 u bj ects  will u n der g o 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 /restricti o ns, a n d f o o d a v oi da nce 
be ha vi ors a n d will be as ke d t o mai ntai n si milar ha bits a n d restricti o ns 
t hr o u g h o ut t he st u d y.  
S u bj ects w h o c o m plete t h r o u g h Da y 1 1 3 ma y ha ve t he o pti on t o recei ve 
A K 0 0 2 i n a se parate o pe n -la bel e xte nsi o n st u d y, if all eli gi bilit y criteria f or t he 
e xte nsi o n st u d y are satisfie d.  S u bjects w h o e nr oll i n t he A K 0 0 2- 0 0 3 X 
e xte nsi o n st u d y will be gi n e xte nsi o n st u d y d osi n g i m me diatel y after c o m pleti n g 
t he Da y 1 1 3 visit of t his pr ot oc ol. S u bjects will n ot c o m plete t he Da y 1 4 1 
pr oce d ures or e xte n de d f oll o w- u p u n der t he A K 0 0 2- 0 0 3 pr ot oc ol. O pe n- la bel 
d osi n g a n d f oll o w - u p i ncl u di n g a n y e xte n de d f oll o w- u p re q uire d t o m o nit or t he 
rec o ver y of l y m p h oc ytes a n d e osi n o p hils will occ ur u n der t he A K 0 0 2- 0 0 3 X 
e xte nsi o n st u d y.  
P ri m ar y O bjecti ve s 
T he pri mar y o bjecti ves of t he st u d y are t o e val uate: 
1)  T he efficac y of A K 0 0 2 i n patie nts  wit h E G a n d/ or  E G E as esti mate d b y 
t he n u m ber of e osi n o p hils per hi g h p o wer fiel d (H P F ) i n gastric  a n d/ or 
d u o de nal bi o psies bef ore a n d after recei vi n g A K 0 0 2 or place b o. 
2)  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 G E .  
Sec o n d ar y 
O bjecti ves  
T he sec o n dar y o bj ecti ves are t o e val uate t he effect s of A K 0 0 2 i n patie nts  wit h 
E G  a n d/ or E G E  b y c o m pari n g A K 0 0 2 t o place b o treat me nt f or t he f oll o wi n g 
para meters:  
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 4  of 9 8  
C o nfi de nti al  
Sec o n d ar y 
O bjecti ves  c o nt. 
1)  
C ha n ges i n s y m pt o ms of E G a n d E G E i n a patie nt re p orte d o utc o me 
( P R O) q uesti o n naire.  
2)  
C ha n ge i n 
. 
3)  
C o m pare res p o n ders bet wee n A K 0 0 2 a n d place b o; a res p o n der is a patie nt 
w h o e x hi bits a > 3 0 % re d ucti o n i n C SI (a b d o mi nal pai n, na us ea, a n d 
diarr hea) a n d a > 7 5 % re d ucti o n i n m uc osal e osi n o p hils.  
E x pl or at or y 
O bjecti ves  
T he e x pl orat or y o bj ecti ves are t o e val uate  t he effect of A K 0 0 2 i n patie nts wit h 
E G  a n d/ or EG E  b y c o m pari n g A K 0 0 2 t o place b o treat me nt f or t he f oll o wi n g 
para meters:  
E x pl or at or y 
O bjecti ves  c o nt. 
1)  
N u m ber of 
 i n patie nts wit h 
. 
2) 
 bef ore a n d after 
treat me nt. 
3) 
C ha n ge i n 
 
, res pecti vel y. 
4)  
C ha n ge i n  
.  
5)  
C ha n ge i n 
 a n d 
 
 
6) 
Sc ori n g of 
 usi n g t he 
 
. 
S af et y O bjecti ves  
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 G E  b y deter mi ni n g A E i nci de nce a n d se verit y, st u d y wit h dra wals d ue t o A Es, 
c ha n ges i n vital si g ns a n d la b orat or y tests, c ha n ges i n c o nc o mita nt m e dicati o n 
use d ue t o A Es , a n d ot her safet y para meters. 
S af et 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 
i nci de nce, relati o ns hi p t o st u d y dr u g, a n d se verit y of T E A Es, wit h dra wals d ue 
t o A Es, a n d c ha n ges i n vital si g ns, la b orat or y tests, c ha n ges i n c o nc o mita nt 
me dicati o n  use d ue t o A Es, i m m u n o ge nicit y a n d ot her safet y para meters.  
Effic ac y E n d p oi nts  
•  
Perce nt c ha n ge fr o m baseli ne i n t he n u m ber of e osi n o p hils i n gastric 
m uc osa or d u o de nal m uc osa. 
•  
Gastr oi ntesti nal s y m pt o mat ol o g y ( P R O q uesti o n naire)  
–  A b d o mi nal pai n 
–  Na usea  
–  V o miti n g  
–  Diarr hea  
–  A b d o mi nal cra m pi n g 
–  Bl oati n g 
–  Earl y satiet y  
–  L oss of a p petite  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 5  of 9 8  
C o nfi de nti al  
Effic ac y E n d p oi nts  
c o nt. 
•  
C ha n ge fr o m baseli ne i n n u m ber of e osi n o p hils i n gastric m uc osa i n 
patie nts wit h E G.  
•  
C ha n ge fr o m baseli ne i n n u m ber of e osi n o p hils i n d u o de nal m uc osa i n 
patie nts wit h E G E . 
•  
C o m pare res p o n ders bet wee n A K 0 0 2 a n d place b o; a res p o n der is a patie nt 
w h o e x hi bits a > 3 0 % re d ucti o n i n C SI (a b d o mi nal pai n, na usea a n d 
diarr hea) a n d a > 7 5 % re d ucti o n i n m uc osal e osi n o p hils. 
•  
C ha n ge fr o m baseli ne i n 
 a bs ol ute c o u nts.  
•  
 
St u d y P o p ul ati o n  
A d ult male a n d fe male patie nts wit h E G  a n d/ or E G E  
P atie nt Selecti o n 
Criteri a  
I ncl usi o n Criteri a 
Patie nts wit h E G  a n d/ or E G E are eli gi ble t o e nr oll i n t he st u d y if all of t he 
f oll o wi n g criteria are met: 
1)  
Male or fe male a ge d ≥1 8 a n d ≤8 0 years at t he ti me of si g ni n g I C F. 
2)  
A vera ge wee kl y sc ore of ≥3 ( o n a scale fr o m 0 – 1 0) rec or de d f or eit her 
a b d o mi nal pai n, diarr hea , a n d/ or na usea o n t he P R O q uesti o n naire d uri n g 
at least 2 wee ks or 2 of t he last 3 wee ks of P R O c ollecti o n. A mi ni m u m of 
4 q uesti o n naires m ust be c o m plete d eac h q ualif yi n g wee k . 
3) 
E osi n o p hilia of t he gastric m uc osa  ≥3 0 e osi n o p hils/H P F i n  5 H P Fs a n d/ or 
e osi n o p hilia of t he d u o de nal m uc osa ≥3 0  e osi n o p hils/H P F i n 3 H P Fs fr o m 
t he E G D perf or me d d uri n g t he scree ni n g peri o d, wit h o ut a n y ot her ca use 
f or t he gastric e osi n o p hilia (e. g., parasitic or ot her i nfecti o n or 
mali g na nc y).  
 
4) 
S u bj ects m ust ha ve faile d or n ot be a de q uatel y c o ntr olle d o n sta n dar d of 
care treat me nts f or E G or E G E s y m pt o ms ( w hic h c o ul d i ncl u de P PIs, 
s yste mic or t o pical c ortic oster oi ds, a n d/ or diet, a m o n g ot hers). 
5)  If o n ot her treat me nts f or E G, E G E, or E o E at e nroll me nt, sta ble d ose f or 
at least 5 half -li ves pri or t o scree ni n g a n d willi n g ness t o c o nti n ue o n t hat 
d ose f or t he d urati o n of t he st u d y.  
6) 
If patie nt is o n pre-e xisti n g dietar y restricti o ns, willi n g ness t o mai ntai n 
dietar y restricti o ns t hr o u g h o ut t he st u d y, as m uc h as p ossi ble.  
7)  
A ble a n d willi n g t o c o m pl y wit h all st u d y pr oce d ures. 
8) 
Fe male s u bjects m ust be eit her p ost - me n o pa usal f or at least 1 year wit h 
F S H le vel > 4 0 mI U/ m L at scree ni n g 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 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 fr o m 
scree ni n g 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. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 6  of 9 8  
C o nfi de nti al  
P atie nt Selecti o n 
Criteri a  c o nt. 
I ncl usi o n Criteri a c o nt. 
 
Male s u bjects 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 fr o m scree ni n g 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. All fertile me n wit h fe male part ners of c hil d beari n g 
p ote ntial s h o ul d be i nstr ucte d t o c o ntact t he I n vesti gat or i m me diatel y if 
t he y s us pect t heir 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.  
 
E xcl usi o n Criteri a  
S u bj ects will be e xcl u de d fr o m t he st u d y if t he y meet a n y of t he f oll o wi n g 
criteria: 
1)  
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. 
2) 
Dia g n osis of celiac disease or acti ve H. pyl ori  i nfecti o n as deter mi ne d b y 
scree ni n g E G D or a hist or y of celiac disease dia g n ose d b y pri or E G D.  
3) 
Prese nce of a b n or mal la b orat or y val ues c o nsi dere d b y t he I n vesti gat or t o 
be cli nicall y si g nifica nt . 
4) 
Gra de  2 or hi g her l y m p h o pe nia ( < 0. 8 × 1 0 9/ L l y m p h oc ytes). 
5) 
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 he s u bject at 
i ncrease d ris k. 
 
6) 
Hist or y of mali g na nc y; e xce pt carci n o ma i n sit u, earl y sta ge pr ostate 
ca ncer , or n o n-mela n o ma s ki n ca ncers. H o we ver, ca ncers t hat ha ve bee n i n 
re missi o n f or m ore t ha n 5 years a n d are c o nsi dere d c ure d, ca n be e nr olle d 
(wit h t he e xce pti o n of breast ca ncer ). All hist or y of mali g na nc y (i ncl u di n g 
dia g n osis, dates, a n d c o m plia nce wit h ca ncer scree ni n g rec o m me n dati o ns) 
m ust be d oc u me nte d a n d certifie d b y t he I n vesti gat or, al o n g wit h t he 
state me nt t hat i n t heir cli nical j u d g me nt t he tiss ue e osi n o p hilia is 
attri b uta ble t o E GI D, rat her t ha n rec urre nce of mali g na nc y.  
7) 
Treat me nt wit h c he m ot h era p y or ra di ot hera p y i n t he prece di n g 6 m o nt hs. 
8) 
Treat me nt f or a cli nicall y si g nifica nt hel mi nt hic parasitic i nfecti o n wit hi n 
6 m o nt hs of scree ni n g a n d/ or a p ositi ve hel mi nt hic test at scree ni n g. 
9) 
Use of a n y me dicati o ns t hat ma y i nterfere wit h t he st u d y s uc h as 
i m m u n os u p pressi ve or i m m u n o- m o d ulat or y dr u gs (i ncl u di n g azat hi o pri ne, 
6- merca pt o p uri ne, met h otre xate, c ycl os p ori ne, 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) or 
s yste mic c ortic oster oi ds wit h a dail y d ose > 1 0 m g of pre d nis o ne or 
e q ui vale nt, d uri n g 5 half-li ves pri or t o scree ni n g or d uri n g t he scree ni n g 
peri o d, e xce pt f or o maliz u ma b ta ke n f or ast h ma a n d/ or urticari a w he n t heir 
ast h ma a n d/ or urticaria ca n n ot be c o ntr olle d o n ot her me dicati o ns, If o n 
o maliz u ma b, t he d ose m ust ha ve bee n sta ble f or at least 4 wee ks pri or t o 
scree ni n g. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 7  of 9 8  
C o nfi de nti al  
P atie nt Selecti o n 
Criteri a  c o nt. 
E xcl usi o n Criteri a  c o nt. 
1 0) Vacci nati o n wit h li ve atte n uate d vacci nes wit hi n 3 0 da ys pri or t o i nitiati o n 
of treat me nt i n t he st u d y, d uri n g t he treat me nt peri o d, or vacci nati o n 
e x pecte d wit hi n 5 half-li ves of t he st u d y dr u g a d mi nistrati o n. 
1 1)  K n o w n hist or y of alc o h ol, dr u g, or ot her s u bsta nce a b use or de pe n de nce. 
1 2) Partici pati o n i n a c o nc urre nt i nter ve nti o nal st u d y wit h t he last i nter ve nti o n 
occ urri n g wit hi n 3 0 da ys pri or t o a d mi nistrati o n of st u d y dr u g ( or 9 0 da ys 
or 5 half-li ves, w hic he ver is l o n ger, f or bi ol o gic pr o d ucts). 
1 3)  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 n t 
w hile partici pati n g i n t he st u d y.  
1 4)  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.  
1 5) Dia g n osis of H y pere osi n o p hilic S y n dr o me ( H E S), base d o n sta n dar d 
criteria ( bl o o d e osi n o p hils > 1 5 0 0 /µ L wit h i n v ol ve me nt of eit her t he heart, 
ner v o us s yste m , a n d/ or b o ne marr o w). 
Test P r o d uct , D ose, 
a n d A d mi nistr ati o n  
A K 0 0 2  
 a n d place b o are s u p plie d as sterile li q ui ds a n d will be 
dil ute d wit h 0. 9 % Na Cl f or i ntra ve n o us (I V) i njecti o n. T he i njecti o n will be 
a d mi nistere d t hr o u g h a n i nf usi o n p u m p, as s pecifie d i n t he P har mac y Ma n ual. 
A K 0 0 2 a n d place b o are f or m ulate d i n 
 
 p H 6. 0, i n water 
f or i njecti o n. 
 
A K 0 0 2 at a d ose of 0. 3 m g/ k g or place b o will be pre pare d acc or di n g t o 
s u bj ect’s b o d y wei g ht a n d a d mi nistere d o n Da y 1. S u bse q ue nt i nf usi o ns of 
A K 0 0 2 at a d ose of 1 m g/ k g or 3 m g/ k g or place b o will be pre pare d o n Da y  2 9 
( ± 3), Da y 5 7 ( ± 3), a n d Da y 8 5 ( ± 3). T he i nitial i nf usi o n s h o ul d be gi ve n o ver 
at least a 5- h o ur peri o d, a n d t he sec o n d a n d t hir d i nf usi o ns s h o ul d be gi ve n 
o ver  at least a 4- h o ur peri o d. T he last i nf usi o n ca n be gi ve n o ver a p pr o xi matel y 
3 – 5 h o urs, de pe n di n g o n t he s u bject’s t olera nce of t he pre vi o us i nf usi o ns a n d at 
t he I n vesti gat or’s discreti o n. 
D ur ati o n of S u bject 
P artici p ati o n  
T he t otal st u d y d urati o n f or eac h s u bject will be a p pr o xi matel y 2 3 – 2 5 wee ks . 
( St u d y d urati o n c o ul d be e xte n de d, as descri be d a b o ve, if t he a bs ol ute 
l y m p h oc yte a n d/ or e osi n o p hil c o u nts ha ve n ot rec o vere d.) T his i ncl u des:  
•  
A scree ni n g peri o d of 1 4 – 3 5  da ys pri or t o st u d y dr u g a d mi nistrati o n. 
•  
A treat me nt peri o d of 8 5 da ys ( ± 3 da ys). 
•  
A f oll o w- u p peri o d of 5 6 da ys ( ± 3 da ys) f oll o wi n g last d ose of A K 0 0 2 ( or 
u ntil l y m p h oc yte a n d e osi n o p hil c o u nts ha ve rec o vere d, if n ot rec o vere d 
d uri n g t he 5 6- da y f oll o w- u p peri o d).  
•  
After t he f oll o w - u p peri o d e n ds o n Da y 1 4 1 or at Earl y T er mi nati o n, if t he 
l y m p h oc yte a n d/ or e osi n o p hil c o u nts ha ve n ot rec o vere d, t he s u bject will 
e nter t he E xte n de d F oll o w- U p peri o d. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 8  of 9 8  
C o nfi de nti al  
D ur ati o n of S u bject 
P artici p ati o n c o nt. 
•  
S u bj ects w h o e nr oll i n t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y will partici pate i n 
t he A K 0 0 2- 0 0 3 st u d y f or 1 9-2 1 wee ks a n d will c o m plete t he st u d y t hr o u g h 
t he Da y 1 1 3 Visit. S u bjects will n ot c o m plete t he Da y 1 4 1 pr oce d ures or 
e xte n de d f oll o w- u p u n der t he A K 0 0 2- 0 0 3 pr ot oc ol. 
S af et y E v al u ati o ns 
Safet y  a n d t olera bilit y will be assesse d t hr o u g h o ut t he st u d y b y m o nit ori n g a n d 
e val uati n g a d verse e ve nts (A Es ), i ncl u di n g a n y c o m plicati o ns res ulti n g fr o m 
t he I V i nf usi o n. All T E A Es will be c ollecte d fr o m t he start of st u d y dr u g 
a d mi nistrati o n t hr o u g h Da y 1 1 3 if e nr olli n g i n t he A K 0 0 2- 0 0 3 X e xte nsi o n 
st u d y, Da y 1 4 1 ( ± 3 da ys) or Earl y T er mi nati o n ( E T).  
Se verit y of A d verse E ve nts will be assesse d usi n g t he Nati o nal Ca ncer I nstit ute 
( N CI) C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E) Versi o n 
5. 0 ( or m ost c urre nt versi o n) . All A Es will be assi g ne d a se verit y gra de a n d will 
be assesse d t o deter mi ne w het her t he y  are cli nicall y si g nifica nt a n d relate d t o 
st u d y dr u g. 
A d diti o nal safet y e val uati o ns i ncl u de cli nical la b orat or y tests, i ncl u di n g a nti -
dr u g a nti b o d y ( A D A) t o A K 0 0 2, c o m plete bl o o d c o u nts, c he mistries, a n d 
uri nal yses  as well as  p h ysical e xa ms ( P Es) a n d vital si g ns fi n di n gs. 
T he Me dical M o nit or will re vie w bli n de d safet y data as it acc u m ulates. T he 
u n bli n de d safet y m o nit or will re vie w u n bli n de d safet y data as it acc u m ulates 
a n d escalate t o t he Me dical M o nit or as a p pr o priate.  
A n i n de pe n de nt Data M o nit ori n g C o m mittee (i D M C) has bee n c o n ve ne d a n d 
will meet at re g ularl y sc he d ule d i nter vals i n acc or da nce wit h t he i D M C c harter.  
D uri n g t he peri o d of E xte n de d F oll o w- U p, data c ollecti o n will be li mite d t o 
he mat ol o g y, S A Es, a n d A d verse E ve nts of S pecial I nterest.  
Effic ac y a n d 
P h ar m ac o d y n a mic 
E v al u ati o ns 
N u m ber of e osi n o p hils i n gastric a n d d u o de nal m uc osa will be e val uate d . I n 
a d diti o n, t he n u m ber of 
 will be e val uate d i n 
patie nts wit h 
 
T he 
 will be c ollecte d. 
Dail y self -a d mi nistrati o n of a disease -s pecific patie nt q uesti o n naire [ P R O 
Q uesti o n naire] will be 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 EG E.  
F or s u bjects wit h c o nc o mita nt a ller gic ast h ma or at o pic der matitis, e val uati o n 
will i ncl u de a  q uesti o n f or eac h a b o ut t he se verit y of s y m pt o ms o ver t he past 
2 4 h o urs. F or s u bjects wit h 
, e val uati o n will i ncl u de a q uesti o n 
a b o ut t he 
 o ver t he past 2 4 h o urs. 
S u bj ects will rate t hei r q ualit y of life usi n g t he n o n-disease -s pecific 
 at 
vari o us st u d y visits.  
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 1 9  of 9 8  
C o nfi de nti al  
P h ar m ac o ki netic 
E v al u ati o ns 
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 date 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 har mac o ki netic ( P K) bl o o d sa m ples will be o btai ne d d uri n g t he scree ni n g 
peri o d a n d pre - d ose o n Da ys 2 9, 5 7, a n d 8 5, a n d a d diti o nall y o n Da ys 1 5, 1 1 3, 
a n d 1 4 1 ( or E/ T). Bl o o d (ser u m) will be c ollecte d f or assess me nt of A K 0 0 2 
a nti- dr u g-a nti b o dies ( A D A) usi n g a vali date d assa y met h o d. A D A bl o o d 
sa m ples will be o btai ne d d uri n g t he scree ni n g peri o d, o n Da ys 1 5, 2 9, 5 7, a n d 
8 5, a n d Da y 1 4 1 ( or E/ T), as well as a n y ti me a n i m m u n o ge nicit y- relate d A E 
occ urs.  
St atistic al A n al ysis  
All s u bj ects w h o recei ve d st u d y me dicati o n will be i ncl u de d i n t he Safet y 
p o p ulati o n f or safet y a nal ysis. S u bjects w h o are ra n d o mize d a n d ha ve recei ve d 
at least o ne d ose of st u d y me dicati o n a n d ha ve a p ost- baseli ne P D or efficac y 
assess me nt will be i ncl u de d i n t he M o difie d I nte nt-t o- Treat ( MI T T) p o p ulati o n 
f or efficac y a nal ysis. 
T he st u d y statisticia n al o n g wit h t he st u d y tea m will re vie w pr ot oc ol de viati o ns 
t o i de ntif y s u bjects t o be e xcl u de d fr o m t he efficac y a nal ysis. All s u bject data 
will be li ste d. 
W he n a p pr o priate, s u m mar y statistics will be pr o vi de d ( 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 f or 
c o nti n u o us varia bles a n d n u m ber a n d perce nta ge of s u bj ects f or cate g orical 
varia bles) b y treat me nt gr o u p f or all meas ures, i ncl u di n g de m o gra p hic a n d 
baseli ne assess me nts, safet y, P D  e val uati o ns, a n d efficac y e n d p oi nts. Baseli ne 
f or all safet y a n d efficac y e n d p oi nts is defi ne d as t he last o bser vati o ns bef ore 
a d mi nistrati o n of t he first I V i nf usi o n of st u d y dr u g , u nless ot her wise s pecifie d. 
N o i m p utati o n will be use d f or missi n g data. 
S u bj ects will be stratifie d at ra n d o mizati o n base d o n t he hi g hest wee kl y 
a vera ge  of t he q ualif yi n g s y m pt o m of disease rec or de d o n t he P R O 
q uesti o n naire d uri n g t he scree ni n g peri o d, t o 1 of 2 gr o u ps, na mel y P R O sc ore 
3. 0 – 4. 9 or 5 . 0 – 1 0. 0. 
Effic ac y A n al ysis: T he pri mar y e n d p oi nt is t he perce nt c ha n ge fr o m baseli ne 
i n t he n u m ber of e osi n o p hils per H P F i n gastric or d u o de nal m uc osa. F or 
s u bj ects w h o pr o vi de gastric or d u o de nal o nl y bi o ps y, t he calc ulati o n will be 
base d o n t he a vera ge c o u nt of t he hi g hest rea di n gs fr o m t he res pecti ve m uc osa 
at baseli ne a n d Da y 9 9. F or s u bjects w h o pr o vi de b ot h gastric a n d d u o de nal 
bi o psies, t he calc ulati o n will be base d o n t he a vera ge c o u nt of t he hi g hest 
rea di n gs fr o m t he c o m bi ne d p o ol of gastric a n d d u o de nal m uc osa. T his 
e n d p oi nt will be s u m marize d b y treat me nt gr o u p. Bet wee n d ose a n d place b o 
gr o u p c o m paris o ns i n t he perce nt c ha n ge will be carrie d o ut b y a nal ysis of 
c o varia nce ( A N C O V A) wit h baseli ne val ue a n d ra n d o mizati o n strat u m as 
c o variates. Se nsiti vit y a nal yses will be carrie d o ut t o de m o nstrate t he 
r o b ust ness of t he treat me nt effect.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 0  of 9 8  
C o nfi de nti al  
St atistic al A n al ysis  
c o nt. 
Gate kee pi n g pr oce d ure is a d de d f or m ulti plicit y a dj ust me nt d ue t o t he 
c o m paris o ns of 2 d ose gr o u ps t o t he place b o gr o u p. 
Met h o d of m ulti ple i m p utati o ns f or missi n g data is a d de d t o t he pri mar y 
e n d p oi nt a n d t he first sec o n dar y e n d p oi nt a nal yses.  
T he t otal s y m pt o m sc ore ( T S S), t he c o m p osite sc ore of i nterest ( C SI), a n d 
d o mai n sc ores of t he P R O s y m pt o m i nte nsities  will be s u m marize d wee kl y f or 
eac h patie nt. T he wee kl y c ha n ge  sc ores will be a nal yze d usi n g t he M M R M  
m o del wit h treat me nt, visit, a n d treat me nt -b y -visit i nteracti o n as fi xe d fact ors, 
baseli ne as c o variate s, a n d s u bj ect as re peate d meas ure u nit. T he c o m paris o n 
bet wee n t he acti ve d ose a n d place b o gr o u ps will be base d o n t he a vera ges of 
t he last 6 wee ks ( Wee ks 9 t hr o u g h 1 4), a n d t he last 2 wee ks ( Wee ks 1 3 a n d 1 4) 
pri or t o bi o ps y, f or wee kl y T S S, C SI, a n d s y m pt o m sc ores usi n g si m ple 
c o ntrasts. Details of t he a nal y tical met h o ds will be i ncl u de d i n t he Statistical 
A nal ysis Pla n ( S A P ).  
A res p o n der a nal ysis c o m p ari n g A K 0 0 2 a n d place b o will be perf or me d. A 
res p o n der is a patie nt w h o e x hi bit a > 3 0 % re d ucti o n i n C SI (a b d o mi nal pai n, 
na usea, a n d diarr hea) a n d a > 7 5 % re d ucti o n i n m uc osal e osi n o p hils.  
Baseli ne f or P R O will be calc ulate d usi n g all P R O assess me nts c ollec te d pri or 
t o ra n d o mizati o n.  
C ha n ge i n t he n u m ber of 
 fr o m baseli ne will be 
a nal yze d usi n g t he sa me M M R M met h o d.  
S af et y A n al ysis: Safet y me as ures i ncl u di n g A Es, i nf usi o n- relate d reacti o ns, 
cli nical la b orat or y tests (i ncl u di n g a nti - A K 0 0 2 a nti b o dies), vital si g ns, p h ysical 
e xa ms, a n d c o nc o mita nt me dicati o n usa ge will be s u m marize d descri pti vel y b y 
treat me nt gr o u p a n d st u d y visit, as a p pr o priate. S hift ta bles will be create d as  
a p plica ble.  
S a m ple S ize: Ass u mi n g a re d ucti o n of 3 0 % i n t he n u m ber of e osi n o p hils per 
H P F ( pri mar y e n d p oi nt) fr o m baseli ne i n t he A K 0 0 2 treate d gr o u p vers us a 
1 0 % re d ucti o n per H P F i n t he place b o gr o u p, ass u mi n g a sta n dar d de viati o n of 
2 0 %, 2 0 s u bjects per gr o u p w o ul d pr o vi de 8 7 % p o wer f or a t w o- si de d test wit h 
a si g nifica nce le vel of 0. 0 5. He nce, 2 0 s u bjects per gr o u p w o ul d be m ore t ha n 
a de q uate fr o m t he efficac y pers pecti ve.  
R ati o n ale f or 
P r ot oc ol 
A me n d me nt  6 
T he f oll o wi n g m o dificati o ns ha ve bee n  i nc or p orate d i nt o A me n d me nt 6: 
•  
U p date d t he c or p orate a d dress f or Alla k os. 
•  
Clarifie d t hat E xcl usi o n Criteria # 2 a p plies t o acti ve H.  pyl ori  i nfecti o n, s o 
t hat i nfecti o n ca n be treate d pri or t o e nr oll me nt. 
•  
A d de d E xcl usi o n Criteria # 1 5 of H y pere osi n o p hilic S y n dr o me ( H E S). 
•  
U p date d E xcl usi o n Criteria # 6 t o reflect t hat carci n o ma i n sit u is n ot 
e xcl usi o nar y, as it is n ot c o nsi dere d t o be ca ncer.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 1  of 9 8  
C o nfi de nti al  
R ati o n ale f or 
P r ot oc ol 
A me n d me nt  6 c o nt.  
•  
U p date d I ncl usi o n Criteria # 2 s o t hat if a s u bject has 2 q ualif yi n g wee ks of 
P R Os, t he y ma y e nter t he st u d y wit h o ut a t hir d wee k of P R Os.  
•  
A d de d a ne w St u d y Wit h dra wal criteri o n: S u bjects, w h o e ntere d t he st u d y 
wit h e osi n o p hil le vels > 1 5 0 0/ µ L at baseli ne, ha d a n I R R d uri n g t he first or 
sec o n d i nf usi o ns, a n d w h ose e osi n o p hil c o u nt was i nitiall y s u p presse d 
after st u d y dr u g b ut t he n re b o u n de d t o > 1 5 0 0 / µ L will be wit h dra w n fr o m 
t he st u d y at t he i nstr ucti o n of t he u n bli n de d safet y m o nit or. 
•  
Re m o ve d t he re q uire me nt t hat vital si g ns nee d t o be c o m plete d after t he 
s u bj ect has bee n i n t he s u pi ne p ositi o n f or > 5 mi n utes. T h e re q uire me nt 
t hat t he s u bject be s u pi ne has bee n re m o ve d si nce s o me i nf usi o n c hairs d o 
n ot f ull y recli ne t o a s u pi ne p ositi o n. T he s u bject s h o ul d be at rest f or 
> 5  mi n utes. 
•  
A n alter nati ve pre me dicati o n re gi me n ma y be use d wit h t he a p pr o val of 
t he Alla k os Me dical M o nit or if it is felt t hat t he patie nt ma y be at 
i ncrease d ris k t o e x perie nce a n i nf usi o n-relate d reacti o n. 
•  
Clarifie d t hat 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 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 de d as a de viati o n 
fr o m t he st u d y. 
•  
Re m o ve d restricti o n o n c offee c o ns u m pti o n o n i nf usi o n da ys t o be 
c o nsiste nt wit h ot her pr ot oc ols a n d si nce n o safet y iss ues ha ve bee n 
o bser ve d. 
•  
Re m o ve d restricti o ns o n stre n u o us e xercise a n d alc o h ol c o ns u m pti o n pri or 
t o bl o o d dra ws t o be c o nsiste nt wit h ot her pr ot oc ols. 
•  
Re m o ve d o pti o nal E xit I nter vie w o n Da y 9 9 as t his is bei n g ca pt ure d i n 
t he E xte nsi o n St u d y i nstea d. 
•  
A d de d D a y 9 9 bl o o d dra w f or he mat ol o g y. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 2  of 9 8  
C o nfi de nti al  
2.  
B ac 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-relat e 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 (S i 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 selecti vel y o n t he s urface of e osi n o p hils, mast cells a n d, at l o wer le vels, o n bas o p hils. 
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 nt ai 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  (I TI M) wit h i n hi bit or y f u n cti o n. E n ga ge me nt of Si glec- 8 i n mast 
cells ca n r es ult i n i n hi biti o n of me diat or rel ease, 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-d e pe n de nt cell ular c yt ot o xicit y ( A D C C)  
a gai nst Si glec - 8-p ositi ve tar get cells i n vi v o a n d i n vitr o. 
2. 2  
O ver vie w of N o nc li nic al St u dies 
A K 0 0 2 is a h u ma nize d n o n- f uc os ylate d I g G 1 a nti b o d y t o t he i n hi bit or y rece pt or Si glec- 8, 
prese nt o n mast cells, e osi n o p hils a n d bas o p hils. Bi n di n g of A K 0 0 2 t o Si glec- 8 i n d uces a si g n al 
t hat i n hi bits mast cell acti vati o n a n d ca n lea d t o a p o pt osis i n e osi n o p hils. I n t he prese n ce of 
effect or cells (s uc h as nat ural killer cells), A K 0 0 2 bi n di n g t o Si glec- 8 de pletes circ ulati n g 
e osi n o p hils b y A D C C . T his pr ofile ma y pr o vi de cli nical be nefit i n diseases i n i n w hic h t hese cell 
t y pes pla y a r ole, s uc h as E G  a n d/ or E G E . 
Si glec - 8 is n ot e x presse d i n s pecies ot her t ha n h u m a ns a n d t heref ore t w o n o vel m o use m o dels 
ha ve bee n de vel o p e 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 bl e of ge nerati n g h u m a n 
i m mu ne cells i ncl u di n g mast cell s 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 has bee n 
e val uate d i n t his m o del. T he sec o n d r o de nt m o del is a tra ns ge nic m o u se li n e 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 he cell s urface i n t hese mice is restricte d t o 
e osi n o p hils, mast cell s, a n d bas o p hils, a patter n of s urface e x pressi o n e q ui v ale nt t o t hat i n 
h u ma ns. A nti- Si glec - 8 a nti b o dies ca n pre v e nt I g E-me diate d a n a p h yla xis i n t his tra ns ge nic m o us e 
li ne, i n dicati n g t hat Si glec- 8 is p har mac ol o gi call y acti ve i n t he m o del. T he a bilit y of A K 0 0 2 t o 
effect  mast cell s a n d e osi n o p hils has bee n e val u ate d i n t his m o del. 
A K 0 0 2 i n hi bits I g E- me di ate d mast cell de gra n ulati o n a n d releas e of t he n e wl y f or me d me diat or 
pr osta gl a n di n D 2 i n vitr o wit h o ut affecti n g mast cell via bilit y. I n t he pres e nce of nat ural killer 
cells, A K 0 0 2 s h o ws p ote nt A D C C acti vit y a gai nst mast cells b ut d oes n ot e x hi bit c o m ple me nt-
de pe n de nt c yt ot o xicit y i n vitr o. I n p eri p heral bl o o d pre parati o ns fr o m n or mal h u ma n d o n ors, 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 3  of 9 8  
C o nfi de nti al  
A K 0 0 2 s h o ws selecti ve d e 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- rel ease 
assa y usi n g i m m o bilize d A K 0 0 2 t o e n ha nce t he 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 p e n de nt release of pr o -i nfl a m mat or y c yt o ki nes.  
T o e val uate 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 us e strai n has bee n de vel o p e d t hat selecti vel y e x presses h u ma n Si gle c- 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- a n d re peat - d ose st u dies 
i n Si glec- 8 tr a ns ge nic mi ce, A K 0 0 2 d e m o nstrate d selecti ve de pleti o n of p erit o neal mast cells a n d 
circ ulati n g a n d tiss ue (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 or at or y Pr actice ( G L P)  t o xicit y a n d t o xic o ki netic st u dies, A K 0 0 2 was 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 he l e vel of t he 
hi g hest d ose pr o p ose d t o be st u die d i n t he 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 mi ce wit h a n e xte n de d ter mi nal half -life esti mate 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 after 
5 wee kl y d oses at t hes e d ose le vels. T here was  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.  Decreas es i n e osi n o p hil c o u nts i n b ot h se x es were o bser v e d, w hic h refl ect 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 v el (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 nic mice w as 1 0 0 m g/ k g, w hic h s u p p orts t he P hase 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 is bei n g st u die d i n a n o n g oi n g first- i n- h u ma n, o pe n-la bel P has e 1 st u d y e val u ati n g 
asce n di n g si n gle d oses a n d m ulti ple d oses of A K 0 0 2 i n patie nts wit h i n d ole nt s yste mic 
mast oc yt osis  ( A K 0 0 2- 0 0 1), a n d a bli n de d, place b o-c o ntr olle d st u d y of asce n di n g si n gle d oses of 
A K 0 0 2 i n healt h y v ol u nteers ( A K 0 0 2- 0 0 2) h as als o bee n c o m plete d . A K 0 0 2 is als o c urre ntl y 
bei n g e val uate d i n 2 o p e n- la bel st u dies, o ne i n c hr o nic urticari a ( A K 0 0 2- 0 0 6) a n d o ne i n se v ere 
aller gic e ye disease ( A K 0 0 2 - 0 0 5).  
Si n gle d oses of 0. 0 0 0 3 – 1 m g/ k g A K 0 0 2 w ere 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 S M. M ulti ple d oses of 0. 3 m g/ k g h a ve bee n a d mi nistere d t o healt h y v ol u nteers a n d 
m ulti ple d oses of 1, 3, 6, a n d 1 0 m g/ k g A K 0 0 2 h a ve bee n a d mi nistere d t o I S M patie nts. I n 
a d diti o n, m ulti ple d oses of u p t o 3 m g/ k g ha ve b ee n a d mi nistere d t o patie nts wit h c hr o nic 
urticaria ( C U) a n d se v ere aller gic e ye disease. A n u m ber of patie nts ha v e recei ve d u p t o 6 
m o nt hl y i nf usi o ns. I n t h ese st u dies, A K 0 0 2 p har m ac o d y na mic ( P D) acti vit y w as o bser v e d f or 
pr ol o n ge d peri o ds of ti m e a n d t he A K 0 0 2 p h ar mac o ki netic ( P K) para meters de m o nstrate d 
. I n I S M patie nts, m o nt hl y i nf usi o ns of 1 m g/ k g 
ha ve bee n a d mi nistere d f or u p t o 6 m o nt hs, a n d m o nt hl y i nf usi o ns of 3 m g/ k g ha v e bee n 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 4  of 9 8  
C o nfi de nti al  
a d mi nistere d f or u p t o 4 m o nt hs. Si n gle d oses of 1 m g/ k g A K 0 0 2 
 
 i n healt h y v ol u nteers a n d i n pati e nts wit h I S M, C U,  a n d s e vere aller gic e ye 
disease.  T o date, 5 1 h ealt h y v ol u nteers 
, 2 5 IS M patie nts , 4 8 urticaria 
patie nts, a n d 3 0 aller gic e ye diseas e patie nts  ha ve bee n e nr olle d i nt o t hes e cli nical st u dies. 
I n ge ner al, A K 0 0 2 w as well t olerate d. I nf usi o n-relate d reacti o ns (I R Rs) w ere o bser ve d i n healt h y 
v ol u nteers, I S M patie nts recei vi n g a first d ose of ≥0. 1 m g/ k g , a n d i n C U  a n d aller gic e ye disease 
patie nts  recei vi n g a first d ose of eit her 0. 3 m g/ k g  or 1  m g/ k g . C o m m o n s y m pt o ms of I R Rs were 
hea dac he, na us ea, s w eati n g, fl us hi n g, a n d re d ness. I nf usi o n -relat e d reacti o ns occ urr i 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, 4 wee ks a part, 
t he sec o n d d ose w as bett er t olerat e d t ha n t he first d ose. T his is als o t he cas e  s o far i n t he 
3 o n g oi n g st u dies i n patie nts wit h I S M, C U , a n d aller gic e ye disea se, wit h  fe wer a d vers e e ve nts 
re p orte d d uri n g t he s ec o n d a n d s u bse q ue nt i nf usi o ns, w he n c o m pare d  t o t he first i nf usi o n. T he 
m ost c o m m o n treat me nt -e mer ge nt a d v erse e ve nts ( T E A Es) o bser ve d w ere hea dac he, u p per 
res pirat or y i nf ecti o n, na usea, s o m n ole nce, l o w er b ac k pai n, s ore t hr oat, t hr o at ti g ht ness, nasal 
c o n gesti o n, a n d li g ht tac h ycar dia. I n b ot h healt h y v ol u nteers a n d I S M, C U, a n d aller gic e ye 
disease  patie nts , t her e was a tra nsie nt decrease i n l y m p h oc yte c o u nt after t h e A K 0 0 2 i nf usi o n 
( us uall y r es ol vi n g wit hi n 1 da y) t hat was n ot ass o ciate d wit h a n y a d v erse e ve nt, a n d a s ustai ne d 
s u p pressi o n i n 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 
cli nicall y si g nifica nt c ha n ges i n vital si g ns, electr ocar di o gra ms ( E C Gs), cli nical la b orat or y 
para meters, a n d p h ysical  e x a mi nati o n were o bser v e 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 Ds ) are c hr o nic i nfl a m mat or y dis or ders c haract erize d 
b y i nfiltrati o n of e osi n o p hils al o n g differe nt se g m e nts of t he gastr oi ntesti nal ( GI) tract , i n t he 
a bse nce o f a n y ca use of t he e osi n o p hilia (Cal d well, 2 0 1 4 ). 
E osi n o p hilic gastritis  ( E G) a n d e osi n o p hilic gastr oe nteritis  ( E G E) re prese nt rare a n d o verla p pi n g 
t y pe of E GI D s t hat are disti nct fr o m E o E (e osi n o p hilic es o p ha gitis) a n d E oC ( e osi n o p hilic 
c olitis). E G  a n d E G E  are c haracterize d b y c hr o nic 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 ( E G) a n d s mall i ntesti ne ( E G E) 
(Pr ussi n, 2 0 1 4 ; Ree d , 2 0 1 5; Z ha n g , 2 0 1 7). E osi n o p hilic i nfiltrati o n is ofte n f o u n d i n b ot h t he 
st o mac h a n d t he s mall i ntesti ne c o nc o mita ntl y ( E G a n d E G E). Di a g n osis is ma de 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 he st o mac h a n d/ or d u o d e n u m wit h o ut a n y ot her ca use f or t he 
e osi n o p hilia. T he gastr oi ntesti nal s y m pt o ms are  b elie ve d t o be d ue t o t he release of i nfla m mat or y 
me di at ors fr o m acti vate d e osi n o p hils, a n d p ossi bl y mast cells a n d ma y var y de p e n di n g o n t he 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 5  of 9 8  
C o nfi de nti al  
la yer a n d/ or l o cati o n of t he e osi n o p hilic i nfiltrate i n t he GI tract. S y m pt o ms c o m m o nl y i ncl u de 
na usea, v o miti n g, a b d o mi nal pai n, diarr hea, bl oati n g, earl y satiet y, 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 ; Ree d , 2 0 1 5). 
J e nse n et al. (2 0 1 6 ) esti mate d t he pre v ale nce of E G a n d E G E 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 et al. ( 2 0 1 7 ) esti mate t he o verall 
pre vale n ce of E G t o be 5. 1/ 1 0 0, 0 0 0 pers o ns.  
T here are n o F D A -a p pr o ve d treat me nts f or E G or E G E . C urre nt t hera pies a n d disease 
ma na ge me nt i ncl u de pr ot o n p u m p i n hi bit ors, a nti hista mi nes, restricte d/ele m e ntal diets, s yste mic 
or oral c ortic ost er oi ds, a n d occasi o nal off-la b el 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 or E G E , alt h o u g h partial be nefit is o bser ve d i n patie nts wit h E o E  (Katz, 2 0 1 3 ). 
Restricte d/ele me ntal diets are n ot c o nsi dere d s ustai na ble f or l o n g-ter m treat me nt a n d are us e d 
m ore s o t o pr o vi de n utriti o n, des pite c o nti n ui n g s y m pt o ms. C ortic oster oi ds, s yste mic or oral, ca n 
pr o vi de s y m pt o m relief, b ut are n ot a s ol uti o n f or l o n g-ter m treat me nt d ue t o t heir n u mer o us si de 
effects.  
B y re d u ci 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 re d uci n g t he n u m ber a n d/ or 
acti vati o n of tiss ue mast cells, A K 0 0 2 ma y be us ef ul i n t he treat me nt of patie nts wit h E G  a n d/ or 
E G E .  
3.  
R ati o n ale f or St u d y a n d D ose Selecti o n  
T he pr o p ose d A K 0 0 2 d oses of 0. 3 m g/ k g a d mi nistere d f or t h e first i nf usi o n, 1 m g/ k g 
a d mi nistere d f or t he s ec o n d i nf usi o n, f oll o we d b y a d ose of eit her 1 m g/ k g or 3 m g/ k g 
a d mi nistere d e ver y 4 wee ks f or 2 s u bse q u e nt i nf usi o ns is base d o n pri or 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 , urticaria, a n d/ or aller gic e ye disease .
 
 
 
 
 
 
 
 
 
 
 
 
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 6  of 9 8  
C o nfi de nti al  
 
 A starti n g d os e of 0. 3 m g/ k g, wit h a sec o n d d ose of 1 m g/ k g, 
f oll o we d b y a d ose of eit her 1 m g/ k g or 3 m g/ k g f or s u bse q ue nt i nf usi o ns, t heref ore, has b ee n 
c h ose n f or t his P hase 2 st u d y wit h A K 0 0 2 i n patie nts wit h E G a n d/ or E G E . 
4.  
St u d y O bjecti ves  
4. 1  
Pri m ar y O bjecti ve  
T he pri mar y o bjecti ves of t he st u d y are t o e v al uat e: 
1)  
T he effi cac y of A K 0 0 2 i n patie nts wit h E G a n d/ or EG E as esti mate d b y t h e n u m ber of 
e osi n o p hils, per H P F  i n gastric a n d/ or d u o de n al bi o psies bef ore a n d after recei vi n g A K 0 0 2 
or place b o. 
2)  
T he safet y  a n d t olera bility of A K 0 0 2 i n patie nts wit h E G a n d/ or EG E . 
4. 2  
Sec o n d ar y O bjecti ves  
T he sec o n d ar y o bjecti ves are t o e v al uate preli mi naril y t he effects of A K 0 0 2 i n patie nts wit h 
E G  a n d/ or E G E b y c o m pari n g A K 0 0 2 t o place b o treat me nt f or t h e f oll o wi n g para meters:  
1)  
C ha n ges i n s y m pt o ms of E G a n d EG E  i n a Patie nt Re p orte d O utc o me ( P R O) q uesti o n naire.  
2)  
C ha n ge i n 
. 
3)  
C o m pare res p o n d ers bet wee n A K 0 0 2 a n d place b o; a res p o n der is a patie nt w h o e x hi bits a 
> 3 0 % re d u cti o n i n C SI ( a b d o mi nal pai n, na usea, a n d diarr h ea) a n d a > 7 5 % re d ucti o n i n 
m uc osal e osi n o p hils. 
4. 3  
E x pl or at or y O bjecti ves 
T he e x pl orat or y o bj ecti v es are t o e val uate t he effect of A K 0 0 2 i n patie nt s wit h E G  a n d/ or EG E  
b y c o m p ari n g A K 0 0 2 t o place b o treat me nt f or t he f oll o wi n g para meters:  
1)  
N u m ber of 
 i n patie nts wit h 
 
2) 
 bef ore a n d after treat me nt. 
3) 
C ha n ge i n 
, res pecti vel y. 
4)  
C ha n ge i n 
. 
5) 
C ha n ge i n 
 a n d 
 
. 
6)  
Sc ori n g of 
 usi n g t he 
 
. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 7  of 9 8  
C o nfi de nti al  
4. 4  
S af et y O bjecti ves  
T o e val uate t he s afet y a n d t olera bility of A K 0 0 2 i n patie nts wit h E G  a n d/ or EG E  b y deter mi ni n g 
A E i nci de nce a n d se v erit y, st u d y wit h dra w als d ue t o A Es, c ha n ges i n vital si g ns a n d la b orat or y 
tests i ncl u di n g i m m u n o ge nicit y, c ha n ges i n c o n c o mita nt me dicati o n use d ue t o A Es, a n d ot her 
safet y par a meters.  
5.  
St u d y Desi g n  
5. 1  
St u d y O ver vie w  
T his is a P hase 2, m ultice nter, ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d st u d y t o e val uat e 
t he efficac y, safet y, t oler a bilit y, a n d p harmac o d y n amic  effect of A K 0 0 2 i n patie nts wit h E G 
a n d/ or E G E.  
Scree ni n g data will be re vie we d t o deter mi ne p atie nt eli gi bilit y. S u bjects  wit h E G a n d/ or E G E  
w h o meet all i ncl usi o n criteria a n d n o ne of t he e x cl usi o n criteria are eli gi ble t o be e nr olle d i nt o 
t he st u d y. S u bject s w h o d o n ot meet all eli gi bilit y criteria at scree ni n g, or w h o q ualif y b ut are n ot 
e nr olle d, ma y be assi g n e d a ne w Patie nt I D n u m b er a n d re- scree n e d o nce. S u bjects  re-scree n e d 
wit hi n 3 0 da ys of si g ni n g t he i nitial c o nse nt will n ot nee d t o si g n a n e w I C F pr o vi di n g t here h a ve 
bee n n o c h a n ges t o t he I C F. S u bjects wit h scree ni n g E G D bi o ps y res ults < 3 m o nt hs pri or t o 
rescr ee ni n g d o not nee d t o u n der g o re p eat pr o ce d ures.  
T he st u d y is desi g ne d as f oll o ws: 
•  
A 1 4 t o 3 5- da y scr ee ni n g peri o d wit h baseli ne e v al uati o ns f or st u d y eli gi bilit y, i ncl u di n g 
baseli ne acti ve s y m pt o ms of di sease ( gat here d b y  P R O c o m plete d d uri n g s cree ni n g ) a n d 
Es o p ha g o- G astr o - Du o de n osc o p y ( E G D) wit h bi o ps y.  
•  
If s u bjects meet hist ol o g y a n d s y m pt o m eli gi bilit y criteria, t he y will recei ve 4 d oses of 
A K 0 0 2 or place b o b y I V i nf usi o n o n Da ys 1, 2 9 ( ± 3), 5 7 ( ± 3), a n d 8 5 ( ± 3).  
•  
A re peat E G D wit h bi o ps y will be perf or me d o n D a y 9 9 ( ± 3).  
•  
S u bjects will be f oll o we d f or 5 6 ( ± 3) d a ys after t he last d ose. F oll o w- u p visits will occ ur o n 
Da ys 1 1 3 ( ± 3) a n d 1 4 1 ( ± 3).  
•  
If t he a bs ol ute l y m p h oc yte a n d/ or e osi n o p hil c o u nts ha ve n ot rec o v ere d  b y Da y 1 4 1 , t he 
f oll o w- u p peri o d will be e xte n de d, a n d s u bjects will be f oll o we d u ntil t he c o u nts ha ve 
rec o vere d. D uri n g t he e xte n de d f oll o w- u p p eri o d, s u bjects will ret ur n t o t he site e ver y 
2 8 da ys ( ± 3) f or a f oll o w - u p safet y visit.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 8  of 9 8  
C o nfi de nti al  
T otal st u d y d urati o n will be u p t o a p pr o xi matel y 2 3 – 2 5 wee ks  (st u d y d urati o n c o ul d be e xte n de d 
as descri be d a b o ve, if t h e a bs ol ute l y m p h oc yte a n d/ or e osi n o p hil c o u nts ha ve n ot rec o v ere d).  
Pre -st u d y m e dicati o ns a n d pre -e xisti n g dietar y restricti 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 u bjects will u n der g o a sta n d ar dize d baseli ne e val uati o n of eati n g ha bits, f o o d 
ha bits/restricti o ns a n d f o o d a v oi da nce b e ha vi ors a n d will be as ke d t o mai ntai n si milar ha bits a n d 
restricti o ns t hr o u g h o ut t h e st u d y.  
S u bjects w h o c o m plete t hr o u g h Da y 1 1 3 ma y h a v e t he o pti o n t o recei v e A K 0 0 2 i n a se parate 
o pe n-la bel e xte nsi o n st u d y , if all eli gi bilit y criteria f or t he e xte nsi o n st u d y are satisfie d. S u bjects 
w h o e nr oll i n t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y will be gi n e xte nsi o n st u d y d osi n g i m me diatel y 
after c o m pleti n g t he Da y 1 1 3 visit of t he A K 0 0 2- 0 0 3 pr ot oc ol. S u bjects will n ot c o m plete t he 
Da y 1 4 1 pr oce d ures or e xte n de d f oll o w- u p u n der t he A K 0 0 2- 0 0 3 pr ot oc ol. O pe n-la bel d osi n g 
a n d f oll o w- u p i ncl u di n g a n y e xte n de d f oll o w- u p re q uire d t o m o nit or t he rec o ver y of 
l y m p h oc ytes a n d e osi n o p hils will occ ur u n der t he A K 0 0 2- 0 0 3 X e xte nsi o n pr ot oc ol. 
5. 2  
Sc he d ule o f E ve nts 
T he o ver all sc he d ule of pr oce d ur es a n d ass ess me nts are de pict e d  i n Ta ble 1 . 
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6  
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 2 9  of 9 8  
C o nfi de nti al  
T a ble 1 
Sc he d ule of Assess me nts  
Assess me nts  
Visits  
Scree ni n g  
( U p t o 5 
We e ks)  
Tre at me nt Peri o d  
( 1 2 Wee ks) 
P ost -Tre at me nt F oll o w -u p Peri o d  
( 8 Wee ks) 
E xte n de d 
F oll o w -u p  
(if nee de d) 
B aseli ne 1 
D a y 1 1 
D a y 4  
( ± 1 d a y) 
D a y 1 5  
( ± 2 d a ys) 
D a y 2 9  
( ± 3 d a ys) 
D a y 5 7  
( ± 3 d a ys) 
D a y 8 5  
( ± 3 d a ys) 
D a y 9 9  
( ± 3 d a ys) 
D a y 1 1 3  
( ± 3 d a ys) 
D a y 1 4 1 
( ± 3 d a ys) 
or E T 3 0 
E ver y  
2 8 D a ys 3 2  
( ± 3 d a ys) 
I nf or me d c o nse nt 
X  
 
 
 
 
 
 
 
 
 
 
De m o gra p hics  
X  
 
 
 
 
 
 
 
 
 
 
Me dical Hist or y  
X  
X  
 
 
 
 
 
 
 
 
 
Pri or/c o nc o mita nt M e dicati o ns 
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
 
B o d y wei g ht a n d hei g ht 2  
X  
X  
 
X  
X  
X  
X  
 
X  
X  
 
Vital Si g ns 3 
X  
X  
 
X  
X  
X  
X  
 
X  
X  
 
1 2 -lea d E C G4 
X  
 
 
 
 
 
 
 
 
 
 
C o m plete P h ysical E xa mi nati o n 5 
X  
 
 
 
 
 
 
 
 
 
 
B aseli ne Diet Assess me nt 6 
X  
 
 
 
 
 
 
 
 
 
 
B aseli ne Diet C o m plia nce 7  
 
X  
 
X  
X  
X  
X  
X  
X  
X  
 
St o ol f or O va a n d P arasite 8, 1 2 
X  
 
 
 
 
 
 
 
 
 
 
e P R O Acti vati o n a n d  Trai ni n g 9  
X  
 
 
 
 
 
 
 
 
 
 
e P R O Q uesti o n naire 1 0  
< -----------------------P erf or m D AI L Y fr o m Scree ni n g t hr o u g h Da y 1 4 1 or 2 8 da ys after last d ose if E T ----------------------->  
 
 
X  
X  ( pre-d os e) 
 
 
X  ( pre-d os e) X  ( pre-d os e) 
X  ( pre-d os e) 
 
X  
X  
 
E G D wit h B i o ps y1 2, 1 3 
X  
 
 
 
 
 
 
X  
 
 
 
 
X  
 
 
 
 
 
 
X  
 
 
 
Ser u m Pre g na nc y test &  F S H 1 2, 1 5 
X  
 
 
 
 
 
 
 
 
 
 
Uri ne P re g na nc y test1 6 
 
X  ( pre-d os e) 
 
 
X  ( pre-d os e) 
X  ( pre-d os e) 
X  ( pre-d os e) 
 
 
X  
 
Eli gi bilit y Assess me nt  
X  
X  
 
 
 
 
 
 
 
 
 
Stratificati o n a n d Ra n d o mizati o n 1 7   
 
X  ( pre-d os e) 
 
 
 
 
 
 
 
 
 
Access I R T -e nter PI D a n d  s u bj ect 
wei g ht  
 
X  ( pre-d os e) 
 
 
X  ( pre-d os e) 
X  ( pre-d os e) 
X  ( pre-d os e) 
 
 
 
 
Access I R T f or first s u bj ect 
scree ne d t o tri g ger first I P s hi p me nt 
X 
 
 
 
 
 
 
 
 
 
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6  
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 0  of 9 8  
C o nfi de nti al  
T a ble 1 
Sc he d ule of Assess me nts  c o nt. 
Assess me nts  
Visits  
Scree ni n g  
( U p t o 5 
We e ks)  
Tre at me nt Peri o d  
( 1 2 Wee ks) 
P ost - Tre at me nt F oll o w -u p Peri o d  
( 8 Wee ks) 
E xte n de d 
F oll o w -u p 
(if nee de d) 
B aseli ne 1 
D a y 1 1 
D a y 4  
( ± 1 d a y) 
D a y 1 5  
( ± 2 d a ys) 
D a y 2 9  
( ± 3 d a ys) 
D a y 5 7  
( ± 3 d a ys) 
D a y 8 5  
( ± 3 d a ys) 
D a y 9 9  
( ± 3 d a ys) 
D a y 1 1 3  
( ± 3 d a ys) 
D a y 1 4 1 ( ± 3 
d a ys) or 
E T 3 0 
E ver y  
2 8 D a ys 3 2 
( ± 3 d a ys) 
Pre me dicati o n wit h cetirizi ne a n d 
aceta mi n o p he n or a p pr o ve d 
alter nati ve 1 8 
 
X  ( pre-d os e) 
 
 
X  ( pre-d os e) 
X  ( pre-d os e) 
X  ( pre-d os e) 
 
 
 
 
St u d y dr u g a d mi nistrati o n 1 9 
 
X  
 
 
X  
X  
X  
 
 
 
 
S y m pt o m -directe d P h ysical E xa m 2 0 
 
X  
 
X  
X  
X  
X  
 
X  
X  
 
C B C wit h differe ntial 1 2, 2 1 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C he mistr y 1 2, 2 2 
X  
X  ( pre-d os e) 
 
X  
X  ( pre-d os e) 
X  ( pre-d os e) 
X  ( pre-d os e) 
 
X  
X  
 
Uri nal ysis 1 2, 2 3 
X  
X  ( pre-d os e) 
 
 
X  ( pre-d os e) 
X  ( pre-d os e) 
X  ( pre-d os e) 
 
X  
X  
 
Ser ol o g y 1 2, 2 4 
X  
 
 
 
 
 
 
 
 
 
 
Bl o o d f or e x pl orat or y safet y 
a nal ysis ( if i n dicate d)1 2, 2 5 
 
X 
 
 
X 
X 
X 
 
 
 
 
Bl o o d f or h ista mi ne a n d tr y ptase (if 
i n dicate d)1 2, 2 5 
 
X 
 
 
X 
X 
X 
 
 
 
 
Bl o o d f or P K a n d st ora ge 1 2, 2 6 
X  
 
 
X  
X  ( pre-d os e) 
X  ( pre-d os e) 
X  ( pre-d os e) 
 
X  
X  
 
Bl o o d f or E x pl orat or y A nal ysis 1 2, 2 7 
 
X  ( pre-d os e) 
 
 
X  ( pre-d os e) 
 
X  ( pre-d os e) 
 
 
X  
 
Bl o o d f or A D A 1 2, 2 8 
X  
 
 
X  
X  ( pre-d os e) 
X  ( pre-d os e) 
X  ( pre-d os e) 
 
 
X  
 
Bl o o d f or T otal Ser u m I g E 1 3, 2 9 
 
X  ( pre-d os e) 
 
 
 
 
 
 
 
X  
 
N o n -seri o us A d verse E ve nts 
 
X  
 
X  
X  
X  
X  
X  
X  
X  
 
A d verse E ve nts of S pecial I nt erest  
 
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Seri o us A d verse E ve nts 3 1 
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
B e gi n A K 0 0 2 -0 0 3 X e xte nsi o n 
st u d y (if a p plica ble) 3 3 
 
 
 
 
 
 
 
 
X 
 
 
A D A :  Anti -A K 0 0 2  a nti b o d y 
E T:  
Earl y T er mi nati o n  
C B C :  Co m plete bl o o d c o u nt  
F S H:  F ollicle -sti m ulati n g h or m o ne 
E C G :  Electr ocar di o gra m 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6  
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 1  of 9 8  
C o nfi de nti al  
T a ble 1 N otes  
1)  
B aseli ne scree ni n g v isit ca n o cc ur o ver se veral da ys wit hi n t he scree ni n g peri o d. Da y 1 ca n be gi n as s o o n as eli gi bilit y criteria are met. 
2) 
At scree ni n g, hei g ht (i n c m) a n d wei g ht (i n k g ) will be rec or de d. B o d y wei g ht will als o be meas ure d o n D a ys 1, 1 5, 2 9, 5 7, 8 5 , a n d o n f oll o w-u p D a ys 1 1 3 a n d 1 4 1 or E T.  
3) 
Vital si g ns will be meas ure d at scree ni n g, Da ys 1 5, 9 9 , 1 1 3 , 14 1  or E T a n d o n all d osi n g da ys pre -d ose, 1 5 mi n utes ( ± 5  mi n utes ) after t he start of st u d y dr u g i nf usi o n, 
i m me diatel y f oll o wi n g t he e n d of i nf usi o n o n treat me nt da ys ( + 5 mi n utes),  1 h o ur  ( ± 1 5 mi n utes) i nt o t he p ost -i nf usi o n o bser vati o n peri o d  a n d j ust pri or t o dis c har ge.  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 be meas ure d  after t he s u bj ect has bee n at rest f or > 5 mi n utes a n d 
bef ore a n y bl o o d dra w.   
4) 
A n E C G will be o btai ne d at scree ni n g bef ore a n y bl o o d is dra w n a n d  after t he s u bj ect has bee n i n t he s u pi ne p ositi o n f or ≥5 mi n utes.  
5) 
A c o m plete p h ysical e xa mi nati o n  will be perf or me d b y eit her t he I n vesti gat or or desi g nee a n d i ncl u de t he f oll o wi n g b o d y s yste m or or ga n assess me nts:  s ki n; hea d, e yes, ears, 
n ose a n d t hr oat; t h yr oi d; l u n gs; car di o vasc ular; a b d o me n; e xtre mities; l y m p h n o des; a n d a brief ne ur ol o gical e xa mi nati o n.  
6) 
A B aseli ne D iet A ssess me nt will be perf or me d usi n g  sta n dar dize d q uesti o ns. Eati n g  patter ns, f o o d a v oi da nce  be ha vi ors , a n d  aller gies will be ca pt ure d.  
7) 
A B aseli ne D iet C o m plia nce c hec k will be perf or me d  a n d a n y varia nces fr o m t he b aseli ne d iet d oc u me nte d.  S u bj ects s h o ul d tr y t o mai ntai n t he baseli ne diet as m uc h as 
p ossi ble t hr o u g h o ut t he st u d y.  
8) 
Fecal c ollecti o n kits f or O va a n d P arasite test will be pr o vi de d t o s u bj ects at scree ni n g. C ollecti o n kits s h o ul d be ret ur ne d  t o t he cli nical site wit hi n 1 da y of c ollecti o n.  
9) 
Acti vate E G /E G E P R O q uesti o n naire a n d pr o vi de s u bj ect wit h u ni q ue user na me a n d  pass w or d.  E G /E G E P R O q uesti o n naire s h o ul d be acti vate d f or all s u bj ects. S u bj ects wit h 
c o nc o mita nt hist or y of at o pic ast h ma, at o pic der matitis a n d/ or e osi n o p hilic es o p ha gitis will recei ve a n e xtra q uesti o n, a b o ut eac h, as a p pr o priate.  
1 0) E G /E G E P R O s h o ul d be c o m plete d ar o u n d t he sa me ti me eac h da y . Pri or t o e nr oll me nt, t he  E G /E G E P R O wee kl y a vera ges o ver t he scree ni n g peri o d  will be calc ulate d a n d 
use d t o assess eli gi bilit y  a n d esta blis h t he baseli ne se verit y of sy m pt o ms.  
1 1) T o be c o m plete d  b y s u bj ect,  i n cli nic, pri or t o a n y bl o o d dra w, p h ysical e xa m , or vital si g n meas ure me nts . 
1 2) S peci me n pr ocesse d b y ce ntral la b.  See ce ntral la b orat or y ma n ual f or c ollecti o n a n d pr ocessi n g details.  
1 3) See A p pe n di x 5  f or bi o ps y ass ess me nts. T he p ost -treat me nt e n d osc o p y ( E G D) a n d bi o ps y assess me nts will be perf or me d o n Da y 9 9  ( ± 3) a n d bi o ps y r es ults will be bli n de d . 
1 4) T o be perf or me d d uri n g t he c o n d uct of t he E G D d uri n g t he s cree ni n g peri o d a n d o n D 9 9.  
1 5) Bl o o d f or ser u m pre g na nc y a n d F S H will be c ollecte d o n scree ni n g, f or s u bj ects of c hil d be ari n g a bilit y or t o s h o w p ost -me n o pa usal stat us.  
1 6) Uri ne f or uri ne pre g na nc y test will be c ollecte d pre -d ose o n all i nf usi o n da ys a n d at E O S. T est kits will be s u p plie d b y t he  ce ntral la b.  T ests will be c o m plete d o n site  a n d 
e val uate d pri or t o i nf usi o n(s).  
1 7)  Stratificati o n base d o n hi g hest wee kl y s y m pt o m a vera ge rec or de d ( gr o u p of 3 . 0– 4 . 9 or 5 . 0– 1 0 . 0). Ra n d o mizati o n a n d s tratificati o n will occ ur t hr o u g h Ce n d uit I R T. 
1 8) Pre me dicati o n re q uire d pri or t o  first a n d sec o n d i nf usi o ns a n d at t he I n vesti gat or’s discreti o n f or  t hir d a n d f o urt h i nf usi o ns, de pe n di n g o n t olera nce of pri or i nf usi o ns.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6  
Date: 0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 2  of 9 8  
C o nfi de nti al  
1 9)  St u d y dr u g will be a d mi nister e d as a si n gle peri p heral I V i nf usi o n o ver at least 5 h o urs  o n st u d y Da y 1 a n d at least 4 h o urs o n  Da y  2 9 ( ± 3  da ys)  a n d Da y 5 7 ( ± 3 da ys) . T he 
i nf usi o n ma y be s h orte ne d t o 3 – 5 h o urs f or D a y 8 5 ( ± 3  da ys) . Please refer t o t he P har mac y Ma n ual f or detaile d i nstr ucti o ns o n st u d y dr u g pre parati o ns, a d mi nistrati o n, a n d 
i nf usi o n rates. 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 of st u d y dr u g. 
2 0)  A s y m pt o m -directe d P E  (incl u di n g assess me nt of p ossi ble i nf usi o n site reacti o ns ) will be perf or me d b y t he I n vesti gat or or desi g nee, as nee de d if  a n y s y m pt o ms are re p orte d.  
2 1)  Bl o o d f or C B C wit h differe nti al, i ncl u di n g a bs ol ute 
 a n d bas o p hil c o u nts, will be o btai ne d j ust pri or t o eac h i nf usi o n, 1 h o ur after t he e n d of eac h i nf usi o n , 
4 h o urs after t he e n d of i nf usi o n  1, as well as d uri n g t he scr ee ni n g peri o d a n d o n D a ys 4, 1 5, 9 9, 1 1 3 , a n d 1 4 1  or E T a n d E xte n de d F oll o w-U p, if a p plica ble . All differe ntial 
bl o o d c o u nts  fr o m Da y 1 (p ost -d ose ) a n d pri or t o Da y 1 4 1 or Earl y T er mi nati o n  will be bli n de d t o t he S p o ns or a n d t he site. A n u nsc he d ule d C B C ma y be c ollecte d at t he 
re q uest of t he u n bli n de d safet y m o nit or. Differe ntial bl o o d c o u nts  will n ot be bli n de d at t he D a y 1 4 1/ E T visit a n d t hese res ults will be use d b y t he sit e t o deter mi ne if t he 
s u bj ect nee ds t o e nter t he E xte n de d F oll o w-U p peri o d.  
2 2)  Bl o o d f or c he mistr y will be o btai ne d pre -d ose o n d osi n g D a ys 1, 2 9, 5 7 , a n d 8 5 , as well as d uri n g t he scree ni n g peri o d a n d o n Da y 1 5, D a y 1 1 3 , a n d Da y 1 4 1  or E T . 
2 3)  Uri ne f or sta n dar d uri nal ysis will be o btai ne d pre -d ose o n d osi n g D a ys 1, 2 9, 5 7 , a n d 8 5, as well as d uri n g t he scree ni n g peri o d a n d o n D a y 1 1 3  a n d Da y 1 4 1  or E T . 
2 4)  Ser ol o g y will i ncl u de H Bs A g, he patitis C a nti b o d y, a nti -H B c, a n d HI V . 
2 5) If a n I nf usi o n-relate d reacti o n ca uses a n i nf usi o n i nterr u pti o n or  cessati o n a sa m ple of bl o o d s h o ul d be o btai ne d f or e x pl orat or y safet y a nal ysis wit hi n 1 – 2 h o ur s of t he o nset 
of t he s y m pt o ms . A sa m ple of bl o o d s h o ul d be o btai ne d f or testi n g of h ista mi ne a n d tr y ptas e le vels wit hi n 1 – 2 h o urs, if a na p h yla xis is s us pecte d.  
2 6) Bl o o d f or P K s h o ul d be o btai ne d pre -d ose o n d osi n g Da ys 2 9, 5 7 , a n d 8 5 , as well as d uri n g scree ni n g a n d o n Da ys 1 5, 1 1 3 , a n d 1 4 1 or E T.   
2 7)  Bl o o d sa m ples f or e x pl orat or y a nal ysis will be c ollecte d pre -d ose o n D a ys 1, 2 9 , a n d 8 5 a n d als o o n D a y 1 4 1 or E T.  
2 8)  Bl o o d sa m ples f or A D A will be c ollecte d d uri n g t he scree ni n g peri o d, o n D a ys 1 5 , 2 9, 5 7, 8 5 a n d Da y 1 4 1 or E T a n d a n yti me a n i m m u n o ge nicit y -relate d A E occ urs.  
2 9)  Bl o o d sa m ples f or T otal S er u m I g E will be c ollecte d o n D a y 1 a n d o n Da y 1 4 1  or E T . 
3 0 ) T he E T Visit s h o ul d be c o n d ucte d 2 8 ( ± 3) da ys after t he 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 earl y ter mi nati o n occ urs 
m ore t ha n 2 8 da ys after t he last d ose of st u d y dr u g, t he n perf or m t he E T v isit as s o o n as p ossi ble. T he pr oce d ures liste d u n der t he fi nal f oll o w -u p visit will be c o n d ucte d 
u nless directe d ot her wise b y t he Me dical M o nit or.  
3 1) T he re p orti n g of Seri o us A d verse E ve nts occ urri n g after si g ni n g I nf or me d c o nse nt a n d pri or t o t he first i nf usi o n will be li mite d t o t h ose t hat relate t o scree ni n g pr oce d ures. 
T he ca pt ure  of all ot her S A Es  a n d A d verse E ve nts t hat are n ot S A Es will be gi n at t he ti me of first i nf u si o n of st u d y dr u g. 
3 2) E xte n de d f oll o w -u p, if nee de d, e ver y 2 8 da ys ( ± 3 da ys) u ntil e osi n o p hil a n d/ or l y m p h oc yte c o u nts ha ve rec o vere d.   
3 3) S u bj ects w h o si g n t he i nf or me d c o nse nt f or t he A K 0 0 2 -0 0 3 X e xte nsi o n st u d y will c o m plete t he pr oce d ures f or Da y 1 1 3 a n d t he n i m me diatel y be gi n o pe n -la bel d osi n g i n t he 
e xte nsi o n st u d y if eli gi ble. S u bj ects will n ot c o m plete t he D a y 1 4 1 pr oce d ures or e xte n de d f oll o w -u p u n der t he A K 0 0 2 -0 0 3 pr ot oc ol . O pe n-la bel d osi n g a n d f oll o w-u p 
i ncl u di n g a n y e xte n de d f oll o w-u p re q uire d t o m o nit or t he rec o ver y of l y m p h oc ytes a n d e osi n o p hils will occ ur u n der t he A K 0 0 2 -0 0 3 X e xte nsi o n pr ot oc ol .  
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 3  of 9 8  
C o nfi de nti al  
6.  
Criteri a f or E v al u ati o n 
6. 1  
S af et y  E n d p oi nt s 
T he safet y a n d t olera bilit y of A K 0 0 2 will be assesse d b y d eter mi ni n g  t he f oll o wi n g:  
•  
P h ysical e x a mi nati o n ( Secti o n  1 1. 3. 2 , 1 1. 3. 5 ) 
•  
C ha n ges i n v ital si gns ( S ecti o n 1 1. 3. 7 ) 
•  
He mat ol o g y ( Secti o n 1 1. 4. 1 ) 
•  
C ha n ges i n c o nc o mita nt me dicati o n use d ue t o A Es ( Secti o n 1 1. 3. 1) 
•  
Bl o o d c he mistr y ( Secti o n 1 1. 5 ) 
•  
Uri nal ysis ( Secti o n 1 1. 5. 2 ) 
•  
A D A ( Secti o n 1 1. 5. 4 ) 
•  
A Es ( Secti o n 1 3 ) i ncl u de se verit y, wit h dra w als d ue t o A Es, a n d ot her s afet y para meters  
6. 2  
P h ar m a c 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 v ali date 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 har mac o ki netic ( P K) bl o o d sa m ples will be o btai ne d o n scree ni n g da y, pre- d ose o n D a ys 2 9, 
5 7, a n d 8 5, a n d a d diti o nall y o n Da y s 1 5, 1 1 3, a n d Da y 1 4 1 ( or E T).  
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 date d  assa y met h o d. A D A 
bl o o d sa m ples will be o btai ne d o n s cree ni n g da y, pre - d ose o n Da y s 2 9, 5 7, a n d 8 5, a n d 
a d diti o nall y o n Da y s 1 5 a n d 1 4 1 ( or E T). A K 0 0 2 c o nce ntrati o ns i n ser u m will be use d t o 
calc ulate A K 0 0 2 e x p os ure.  
6. 3  
Effic ac y  E n d p oi nts  
Pri mar y E n d p oi nt 
•  
Perce nt c h a n ge fr o m bas eli ne i n t he n u m ber of e osi n o p hils per H P F  i n gastric or d u o de n al 
m uc osa. F or s u bj ects w h o pr o vi de b ot h gastric a n d d u o de nal bi o psies, t he calc ulati o n will 
be base d o n t he a ver a ge c o u nt of t he hi g h est rea di n gs fr o m t he c o m bi ne d p o ol of gastric 
a n d d u o de nal m uc osa. 
Sec o n dar y E n d p oi nts 
•  
C ha n ges fr o m bas eli ne i n t he wee kl y a v era ges of s y m pt o ms as meas ure d b y t he P R O 
Q uesti o n naire t otal a n d it e m dail y sc ores f or 8 differe nt s y m pt o ms:  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 4  of 9 8  
C o nfi de nti al  
–  A b d o mi nal pai n i nte nsit y 
–  Na usea  i nte nsit y 
–  V o miti n g  i nte nsit y 
–  V o miti n g fre q u e nc y 
–  Diarr hea  i nte nsit y 
–  Diarr hea fr e q ue n c y  
–  Earl y satiet y  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 ge fr o m bas eli ne i n t he n u m ber of e osi n o p hils i n gastric m uc os a i n patie nts wit h  E G.  
•  
C ha n ge fr o m bas eli ne i n t he n u m ber of e osi n o p hils i n d u o de nal m uc osa i n patie nts wit h  
E G E.  
•  
C o m pare res p o n d ers bet wee n A K 0 0 2 a n d place b o; a res p o n der is a patie nt w h o e x hi bits a 
> 3 0 % re d u cti o n i n C SI ( a b d o mi nal pai n, na usea, a n d diarr h ea) a n d a > 7 5 % re d ucti o n i n 
m uc osal e osi n o p hils. 
•  
C ha n ge i n 
. 
6. 4  
E x pl or at or y E n d p oi n ts 
•  
C ha n ge fr o m bas eli ne i n t he n u m ber of 
 i n patie nts wit h 
 
•  
 bef ore a n d after treat me nt. 
•  
C ha n ge i n 
, res pecti vel y. 
•  
C ha n ges i n  
. 
•  
C ha n ge i n 
 a n d 
 
. 
•  
Sc ori n g of 
 usi n g t he 
 
. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 5  of 9 8  
C o nfi de nti al  
7.  
P ati e nt Selecti o n  
7. 1  
N u m ber of P atie nt s 
A t otal of a p pr o xi matel y 6 0 s u bjects will be d ose d i n t he st u d y i n w hic h 2 0 s u bjects wil l recei ve 
A K 0 0 2  at a d ose of 0. 3 m g/ k g f or t he first d ose f oll o we d b y 1 m g/ k g f or 3 s u bse q ue nt d oses, 
2 0 s u bjects will recei ve A K 0 0 2 at a d ose of 0.3 m g/ k g f or t he first d ose, f oll o we d b y 1 m g/ k g f or 
t he sec o n d d ose a n d 3 m g/ k g f or 2  s u bs e q ue nt d oses, a n d 2 0 s u bjects will recei v e place b o , i n a 
ra n d o mize d, d o u ble- bli n d fas hi o n.  
7. 2  
St u d y P o p ul ati o n  
Male a n d f e male E G  a n d/ or E G E patie nts, a ge d ≥1 8 a n d ≤8 0 years w h o f ulfill t he eli gi bilit y 
criteria s pecifie d bel o w.  
7. 3  
I ncl usi o n Criteri a 
Patie nts wit h a dia g n osis of E G  or E G E are eli gi bl e f or e nr oll me nt i nt o t he st u d y if all of t he 
f oll o wi n g criteria are met: 
1) 
Male or fe m ale a ge d ≥1 8 a n d ≤8 0 years at t he ti me of si g ni n g I C F. 
2)  
A vera ge wee kl y s c ore of ≥3 ( o n a scale fr o m 0 – 1 0) rec or ded f or eit her a b d o mi nal pai n, 
diarr hea a n d/ or na us ea o n t he P R O q uesti o n naire d uri n g at least 2 wee ks or 2 of t he last 
3 wee ks of P R O c ollecti o n. A mi ni m u m of f o ur q uesti o n naires m ust be c o m plete d eac h 
q ualif yi n g  w ee k.  
3)  
E osi n o p hilia of t he gastri c m uc osa ≥3 0 e osi n o p hi ls/H P F  i n 5 H P Fs  a n d/ or e osi n o p hilia of 
t he d u o de nal m uc osa ≥3 0 e osi n o p hils/ H P F i n 3  H P Fs fr o m t he E G D p erf or me d d uri n g t he 
scree ni n g p eri o d, wit h o ut a n y ot h er ca use f or t he gastric e osi n o p hilia (e. g., parasitic or 
ot her i nfecti o n or mali g n a nc y ). 
4)  
S u bjec ts m ust ha ve faile d or n ot be a de q u atel y c o ntr olle d o n sta n dar d- of-care treat me nts f or 
E G  or E G E  s y m pt o ms ( w hic h c o ul d i ncl u de P PIs, s yste mic or t o pical c orti c oster oi ds, 
a n d/ or diet, a m o n g ot hers).  
5)  If o n ot her tr eat me nts f or E G,  E G E , or E o E at e nr oll me nt, sta ble d ose f or at least 5 half-
li ves pri or t o scree ni n g a n d willi n g ness t o c o nti n ue o n t hat d ose f or t he d urati o n of t he 
st u d y.  
6) 
If s u bject is o n pre-e xisti n g dietar y restri cti o ns, willi n g ness t o mai ntai n dietar y restri cti o ns 
t hr o u g h o ut t he st u d y, as m uc h as p ossi ble. 
7) 
A ble a n d willi n g t o c o m pl y wit h all st u d y pr oce d ures.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 6  of 9 8  
C o nfi de nti al  
8) 
Fe male s u bjects m ust be eit her p ost-me n o pa us al f or at least 1 year wit h F S H le vel 
> 4 0  mI U/ m L at scr ee ni n g or s ur gicall y sterile (t u bal li gati o n, h ysterect o m y or bil ateral 
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 v e a ne gati ve 
pre g na nc y t est a n d a gr ee 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 fr o m scree ni n g 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 h e ver is l o n ger.  
 
Male s u bjects  wit h fe mal e 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 ntr ace pti o n fr o m scree ni n g 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 h e ver is l o n ger. All fertile me n wit h fe male 
part ners of c hil d beari n g p ote ntial s h o ul d be i nstr ucte d t o c o ntact t he I n vesti gat or 
i m me diatel y if t he y s us p ect t heir 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 x cl u de d fr o m t he st u d y if t h e y meet a n y of t he f oll o wi n g criteria:  
1)  
K n o w n h y p erse nsiti vit y t o a n y c o nstit ue nt of t he st u d y dr u g. 
2) 
Dia g n osis of celiac dis ease or acti ve H. pyl ori  i nfecti o n as deter mi ne d b y scree ni n g E G D or 
a hist or y of celiac diseas e dia g n ose d b y pri or E G D.  
3) 
Prese nce o f a b n or m al la b orat or y val ues c o nsi dere d b y t he I n vesti gat or t o b e cli nicall y 
si g nifica nt. 
4) 
Gra de 2 or  hi g h er l y m p h o pe nia ( < 0. 8 × 1 09/ L l y m p h oc yt es). 
5) 
A n y disease or c o n diti o n ( me dical or s ur gi cal) 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 he s u bject at i ncrease d ris k . 
6) 
Hist or y of m ali g na n c y; e x ce pt carci n o ma i n sit u, earl y sta ge pr ostate ca ncer , or 
n o n- mela n o ma s ki n ca n cers. H o we v er, ca ncers t h at ha ve bee n i n re missi o n f or m ore t ha n 
5 years a n d are c o nsi der e d c ure d, ca n be e nr olle d ( wit h t he e x ce pti o n of breast ca ncer). All 
hist or y of mali g na n c y (i n cl u di n g dia g n osis, dates, a n d c o m plia nce wit h ca n cer scree ni n g 
rec o m me n dati o ns) m ust be d oc u me nte d a n d certifie d b y t he I n vesti gat or, al o n g wit h t he 
state me nt t hat i n t heir cli nical j u d g me nt t he tiss ue e osi n o p hilia is attri b uta ble t o E GI D, 
rat her t ha n rec urre n ce of mali g na n c y.  
7)  
Treat me nt wit h c h e m ot hera p y or ra di ot hera p y i n t he prece di n g 6 m o nt hs. 
8) 
Treat me nt f or a cli nicall y si g nifica nt h el mi nt hic parasitic i nfecti o n wit hi n 6 m o nt hs of 
scree ni n g a n d/ or a p ositi ve hel mi nt hic test at scree ni n g. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 7  of 9 8  
C o nfi de nti al  
9) 
Use  of a n y me di cati o ns t hat ma y i nterfere wit h t h e st u d y s uc h as i m m u n os u p pressi ve or 
i m m u n o m o d ulat or y dr u gs (i ncl u di n g azat hi o pri ne, 6- merca pt o p uri ne, met h otrex ate, 
c ycl os p ori ne, 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) or s yste mic c ortic oster oi ds wit h a dail y d ose > 1 0 m g of 
pre d nis o ne or e q ui vale nt, d uri n g 5 h alf-li ves pri or t o scree ni n g or d uri n g t h e scre e ni n g 
peri o d , e x ce pt f or o maliz u ma b ta ke n f or ast h ma a n d/ or urticaria w h e n t heir ast h ma a n d/ or 
urticaria ca n n ot be c o ntr olle d o n ot her me dicati o ns. If o n o maliz u ma b , t he d ose m ust ha ve 
bee n  sta ble f or at least 4 wee ks pri or t o scree ni n g.  
1 0) Vacci n ati o n wit h li ve atte n uate d vacci nes wit hi n 3 0 da ys pri or t o i nitiati o n of treat me nt i n 
t he st u d y, d uri n g t he tr eat me nt peri o d, or vacci nati o n e x pecte d wit hi n 5 half-li ves of t he 
st u d y dr u g a d mi nistrati o n. 
1 1)  K n o w n hist or y of alc o h ol, dr u g, or ot h er s u bsta nce a b use or d e pe n d e nce. 
1 2) Partici pati o n i n a c o nc urr e nt i nter ve nti o nal st u d y wit h t he last i nter ve nti o n occ urri n g wit hi n 
3 0 da ys pri or t o a d mi nistrati o n of st u d y dr u g ( or 9 0 da ys or 5 half- li ves, w hic he ver is 
l o n ger, f or bi ol o gic pr o d ucts). 
1 3)  W o me n w h o are pr e g na nt, breastfee di n g, or pla n ni n g t o bec o m e pre g n a nt w hile 
partici pati n g i n t he st u d y.  
1 4)  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.  
1 5)  Dia g n osis of H y per e osi n o p hilic S y n dr o me ( H E S) , base d o n sta n dar d criteri a ( bl o o d 
e osi n o p hils > 1 5 0 0/ µ L wit h  i n v ol ve me nt of eit her t he heart, n er v o us s yste m, a n d/ or b o ne 
marr o w).  
8.  
Pri or a n d C o nc urre nt Me dic ati o ns  
Pri or a n d c o nc o mita nt m e 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 be rec or d e d i n t he El ectr o nic Case R e p ort F or ms (e C R Fs) f or 3 0 d a ys pri or t o  t he scree ni n g 
visit.  
A n y me di cati o n m ust ha ve bee n st o p pe d as re q uire d i n E x cl usi o n Criteria . S u bjects  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, 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 v esti gat or, u nless t he ne w me dicati o n is re q uire d f or e mer ge n c y use. 
I m me diat el y pri or t o t he first i nf usi o n, the st u d y site pers o n nel s h o ul d e ns ure t hat t he s u bject 
c o nti n ues t o meet t he I ncl usi o n criteria a n d n o ne of t he E x cl usi o n criteria (i ncl u di n g n o recei pt 
or use of pr o hi bite d me di cati o ns).  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 8  of 9 8  
C o nfi de nti al  
All me dicati o ns ta ke n f or t he 3 0 da ys bef ore scree ni n g a n d d uri n g p artici pati o n i n t his st u d y 
m ust be d oc u me nte d o n t he e C R F. All me dicati o ns use d t o treat I R Rs or A Es m ust als o be 
d oc u me nte d. 
8. 1  
Pr o hi bite d  Me dic ati o ns  
A n y me di cati o ns t hat ma y i nterfer e wit h t he st u d y s uc h as i m m u n os u p pressi ve or 
i m m u n o m o d ulat or y dr u gs (i ncl u di n g azat hi o pri ne, 6- merca pt o p uri ne, met h otre x ate, 
c ycl os p ori ne, 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 ) or s yste mic c ortic oster oi ds wit h a dail y d ose > 1 0 m g of pre d nis o ne or e q ui vale nt. 
T he use of o maliz u ma b b y ast h ma a n d/ or urtic aria patie nts f or ast h ma a n d/ or urticaria t h at 
ca n n ot be c o ntr olle d o n ot her me dicati o ns is all o w e d, as l o n g as t he d ose h a s bee n  sta ble f or at 
least 4 wee ks pri or t o scr ee ni ng,  a n d e x pecte d t o re mai n sta ble t hr o u g h o ut t he st u d y.  
8. 2  
All o w e d Me dic ati o ns  
M e 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, 
le u k otrie ne a nta g o nist 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 ores ee n me dical necessit y, d oses are t o re mai n sta ble.  All me dicati o n use will be 
d oc u me nte d i n t he e C R F. 
9.  
St u d y Tre at me nt  
9. 1  
F or m ul ati o n of Test Pr o d uct  a n d Pl ace b o  
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 -us e 1 0 R gl ass 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° C t o 8° C. T he A K 0 0 2 f or m ulati o n is 
 
, p H 6. 0, i n steril e water f or i njecti o n.  
Place b o is s u p plie d as a sterile li q ui d i n a si n gle - us e 1 0 R glass vial wit h a fill v ol u me of 
a p pr o xi matel y 1 0. 6 m L.  Place b o c o ntai ns 
 
, p H 6. 0, i n sterile wat er f or i njecti o n.  
N ote :  A K 0 0 2 a n d place b o will be referre d t o as “st u d y dr u g. ” 
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 - us e 1 0 R gl ass vial wit h a fill 
v ol u me of a p pr o xi matel y 1 0. 6 m L . Eac h vial will be la bele d wit h t he re q uire d i n vesti gati o nal us e 
state me nt, l ot n u m ber, kit n u m ber, S p o ns or na me, a n d directi o ns f or st ora ge. Eac h vial will als o 
c o ntai n a tear- off la bel wit h kit n u m ber a n d s pace t o d oc u me nt s u bject I D a n d pre parati o n date. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 3 9  of 9 8  
C o nfi de nti al  
T his tear - off la bel s h o ul d be a p plie d t o t he I P D os e Calc ulati o n a n d Pre p arati o n W o r ksheet a n d 
mai ntai ne d wit h t he U N B LI N D E D s o urce d oc u m e nts, a wa y fr o m all bli n de d staff.  
Glass vials are pl u g ge d wit h Tefl o n -c oat e d r u b ber st o p pers a n d seale 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 Site  
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 sites. T he 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 o c u me ntati o n a n d a p pr o vals ha ve b ee n 
recei v e d b y t he S p o ns or, c o ntract has b ee n e x ec ute d , a n d t he first scree n e d s u bject is e ntere d i nt o 
t he I R T. S u bse q u e nt st u d y dr u g s hi p me nts will be tri g gere d a ut o maticall y b ase d o n 
pre deter mi ne d s u p pl y le v els 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/ D os a ge Re gi me n 
S u bjects will be ra n d o ml y assi g ne d t hro u g h t he I R T s yste m t o d osi n g gr o u ps of 1 m g/ k g A K 0 0 2  
(first d ose at 0. 3 m g/ k g), 3 m g/ k g A K 0 0 2  (first d ose at 0. 3 m g/ k g, sec o n d d ose at 1 m g/ k g ), or 
place b o. T he e x act d ose will be calc ulate d pri or t o eac h i nf usi o n a n d b ase d o n c urre nt s u bject 
wei g ht . St u d y dr u g will b e a d mi nistere d as a si n gl e peri p heral I V 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 he st u d y P har mac y  Ma n ual o n Da ys 1, 2 9 ( ± 3), 5 7 ( ± 3), a n d 8 5 ( ± 3). 
9. 5  
Pre p ar ati o n of St u d y Dr u g  
A n u n bli n de d st u d y p har macist or desi g n ee will pre pare t he st u d y dr u g f or eac h i nf usi o n. T his 
u n bli n de d p har macist/ desi g nee m ust n ot partici p ate i n a n y st u d y-relate d acti vities w here bli n di n g 
is re q uire d. Base d o n s u bject wei g ht o btai ne d t he da y of d osi n g, t h e desi g n ate d st u d y p h ar macist 
will pre pare t h e a p pr o priate dil uti o n of A K 0 0 2 f or I V 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 p are d acc or di n g t o t he 
p har mac y ma n u al f or A K 0 0 2. Please refer t o t he P har mac y Ma n u al 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. 
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 n eral, st u d y dr u g will be i nf use d t hr o u g h a p eri p heral vei n 
i ntra ve n o us (I V) set. T he I V li ne will be ke pt o pe n bef ore a n d aft er 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.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 0  of 9 8  
C o nfi de nti al  
A v ol u me of 1 0 0 m L *  of t he calc ulate d d os e of st u d y dr u g will be i nf use d o ver at least 5 h o urs 
o n St u d y Da y 1, o ver at l east 4 h o urs o n St u d y D a ys 2 9 a n d 5 7, a n d o ver at least 3 h o urs o n 
St u d y Da y 8 5. If t he i nf usi o n is sl o we d or i nterr u pte d, t he ti me ma y b e e xte n de d l o n ger t ha n 
5 h o urs, as l o n g as it d oes n ot e x cee d 8 h o urs. 
F or t he fir st a n d sec on d i nf usi o ns of st u d y dr u g, s u bjects will be pre me dicate d wit h cetirizi ne a n d 
aceta mi n o p he n , or a n alt er nati ve pr e me dicati o n a p pr o ve d b y t he Alla k os Me dical M o nit or. If t he 
first 2 i nf usi o ns are w ell t olerate d, it is at t he I n vesti gat or’s discreti o n w het her t o pre me di cate f or 
t he t hir d a n d f o urt h i nf usi o ns.  
T he I V i nf usi o n ma y be i nterr u pte d, a n d/ or t h e rat e ma y be re d uce d if a s u bject  has  a n i nf usi o n-
relate d r eacti o n (I R R). T he ti me t he 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 h e i nf usi o n is restarte d after a n i nterr u pti 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 p arati o n. A d mi nistrati 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 v esti gat or, 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 he 
i nf usi o n ca n n ot be c o m pl ete 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 s u bject 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.  
If t he s u bject e x perie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y dr u g 
i nf usi o n, a n 1 1 m L bl o o d sa m ple s h o ul d be c ollect e d wit hi n 1 – 2 h o urs of t he o nset of s y m pt o ms, 
f or e x pl orat or y saf et y a n al ysis. If t h e s u bject e x perie nces si g ns or s y m pt o ms of a na p h yla xis, a 
bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of s y m pt o ms f or t he a nal ysis of 
hista mi ne a n d tr y pt ase le vels.  
T he s u bject will be o bser ve d f or 4 h o urs after t h e e n d of t he first a n d s ec o n d  i nf usi o ns, a n d if n o 
iss ues are n ote d, will be o bser ve d f or 2 – 4 h o urs f or s u bse q ue nt i nf usi o ns, as per I n v esti gat or 
discreti o n. 
*   D ue t o 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 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 de d as a 
de viati o n fr o m t he st u d y. 
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 he st u d y sites at 2° C t o 8º C u n der l oc k at t he desi g nat e d p har mac y. 
Access will be restricte d t o  desi g nate d  p h ar mac y staff. T he N a Cl 0. 9 % will be st ore d at a m bie nt 
te m perat ur e, per ma n ufact urer’s re q uire me nts. All st u d y dr u g a n d N a Cl will be st ore d i n a n area 
t hat 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 x cee ds or falls bel o w t his ra n ge, t his wi ll be re p orte d t o t he S p o ns or or 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 1  of 9 8  
C o nfi de nti al  
desi g nee a n d ca pt ur e d as a de viati o n. T he S p o ns or will n otif y t h e site if t he st u d y dr u g is t o be 
q uara nti ne d or ca n b e use d. 
9. 8  
St u d y Dr u g Acc o u nt a bilit y  
T he site’s st u d y p h ar 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 for t h e recei pt, dis pe nsi n g, pre p arati o n, use, ret ur n ( or destr u cti o n) a n d fi nal 
dis p ositi o n of all I P. All d osa ge cal c ulati o ns will be d oc u me nte d o n t he s o urce d oc u m e nts. T he 
Master I P A cc o u nta bilit y L o g s h o ul d be us e d t o ca pt ure recei pt, dis pe nsi n g a n d ret ur n ( or 
destr ucti o n). T he u n bli n d e d st u d y m o nit or will verif y e ntries o n t hese d o c u me nts t hr o u g h o ut t he 
c o urse of t he st u d y.  
All st u d y dr u g acc o u nta bilit y l o gs will be c o nsi dere d U N B LI N DI N G a n d m ust be mai ntai ne d 
u n der sec ure st ora ge l ocati o ns, a wa y fr o m a n y bli n de d st u d y acti vit y. 
1 0.  S u bject 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  S u bject  N u m beri n g  
Eac h s u bject  w h o pr o vi des i nf or me d c o ns e nt will be assi g n e d a p atie nt i de ntificati o n n u m ber 
( PI D) t hat u ni q uel y i de ntifies t he m as a s u bject i n t he st u d y. T he PI D will c o nsist of a 9-di git 
n u m ber: 
•  
T he first 3 di gits desi g nat e t he st u d y n u m ber. F or t his st u d y, t h e n u m ber is 2 0 3. 
•  
T he sec o n d 3 di gits desi g nate t he site n u m ber. 
•  
T he last 3 di gits desi g nat e t he or der of c o ns e nt at t he site (t he first s u bject w h o pr o vi des 
c o nse nt is 0 0 1, t he sec o n d s u bject is 0 0 2, a n d s o f ort h). 
T he s u bject will mai ntai n t he sa me PI D t hr o u g h o ut t he e ntire st u d y . If a s u bject si g ns t he I C F b ut 
d oes n ot meet t he i ncl usi o n/e x cl usi o n criteria or q ualifies f or t he st u d y b ut d oes n ot e nr oll, t he 
s u bject ma y b e assi g ne d a ne w PI D a n d re-scree n e d o nce. S u bjects  re-scree ne d wit hi n 3 0 da ys of 
si g ni n g t he i nitial c o nse nt will n ot nee d t o si g n a n e w I C F pr o vi di n g t here h a ve bee n n o c ha n ges 
t o t he I C F. 
1 0. 2  Str atific ati o n  a n d R a n d o miz ati o n 
T o be ra n d o mize d i nt o t he st u d y, a s u bject m ust ha ve a n a vera ge w ee kl y sc ore of ≥3 ( o n a scale 
fr o m 0– 1 0) rec or d e d f or eit her a b d o mi nal pai n, di arr hea a n d/ or n a usea o n t he P R O q uesti o n naire 
d uri n g at least 2 wee ks of P R O c ollecti o n. A mi ni m u m of 4 q uesti o n naires m ust be c o m plete d o n 
eac h q u alif yi n g w ee k . S u bjects will be ra n d o mize d t hr o u g h t he I nteracti ve Res p o nse Tec h n ol o g y 
(I R T) s yste m. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 2  of 9 8  
C o nfi de nti al  
If t he s u bject q ualifi es f or t he st u d y after c o m pleti n g all of t he s cree ni n g pr oce d ures, o n t h e da y 
of first i nf usi o n  ( St u d y D a y 1), t he site will access t he I R T s yste m  i n or d er t o ra n d o mize a n d 
stratif y t he s u bj ect i n t he st u d y a n d e nter t he c urre nt b o d y wei g ht f or st u d y dr u g d os e cal c ulati o n. 
T he site will i de ntif y t he hi g hest a v era ge  wee kl y sc ore f or a n y q ualif yi n g s y m pt o m of disease 
rec or d e d d uri n g t he scree ni n g peri o d i n or d er t o stratif y s u bjects t o 1 of 2 gr o u ps, na mel y P R O 
sc ore 3– 4. 9 or 5 . 0 – 1 0. 0. The I R T s yst e m will t he n ra n d o ml y assi g n t he s u bj ect t o A K 0 0 2 at a 
d ose of 0. 3 m g/ k g ( first d ose) f oll o we d b y 1 m g/ k g (s u bs e q ue nt d oses), A K 0 0 2 at a d ose of 
0. 3 m g/ k g ( first d ose), 1 m g/ k g (sec o n d d ose), f oll o we d b y 3 m g/ k g (s u bse q ue nt d oses), or 
place b o i n a d o u b le- bli n d fas hi o n a n d will se n d a n e mail t o t he u n bli n de d p har macist detaili n g 
t he treat me nt assi g n me nt.  
T we nt y s u bj ects will be r a n d o mize d t o treat me nt wit h A K 0 0 2 at a d ose of 0. 3 m g/ k g  first d ose/ 
1 m g/ k g  s u bse q ue nt d oses; 2 0 s u bjects ra n d o mize d t o A K 0 0 2 at a d ose of 0. 3 m g/ k g first d ose/ 
1 m g/ k g  sec o n d d os e/ 3 m g/ k g s u bse q ue nt d os es; a n d 2 0 s u bjects ra n d o mize d t o place b o. 
A s u bject is c o nsi dere d e nr olle d i n t he trial w he n t he s u bject is ra n d o mize d. 
F or s u bse q u e nt i nf usi o ns o n Da y s 2 9, 5 7, a n d 8 5, t he c o or di nat or will access t he I R T o n t he d a y 
of i nf usi o n a n d e nter t h e PI D  as well as t he s u bject ’s b o d y w ei g ht , a n d t he s yste m will assi g n t h e 
s u bject t he d ose acc or di n g t o t heir r a n d o mizati o n n u m ber. T he u n bli n de d p har macist will t he n 
recei v e a n e m ail detaili n g t he kit n u m ber t o pre pare. 
Pri or t o eac h i nf usi o n , t h e I n vesti gat or or d esi g n ee will c o nfir m t he PI D  rec or de d o n t he I V ba g 
pr o vi de d b y t he u n bli n de d p har macist matc h es t he s u bject. T he s u bject i de ntificati o n s h o ul d be 
c o nfir me d a n d d o c u me nt e d b y a sec o n d part y pri or t o a d mi nisteri n g t he i nf usi o n, w he ne ver 
p ossi ble. Neit her t he treat me nt gr o u p n or t h e d ose pre pare d ( 0. 3, 1, or 3 m g/ k g or place b o) 
s h o ul d e ver be rec or de d o n t he I V i nf usi o n ba g.  
T he assi g n me nt of treat me nts t o A K 0 0 2 or place b o will be sec urel y retai ne d i n t he I R T s yste m 
u ntil s uc h ti me as desi g n ate d b y t he Statistical A nal ysis Pla n.   
1 0. 3  Bli n di n g  
T he i de ntit y of t est a n d c o ntr ol treat me nts will n ot be k n o w n t o I n vesti gat ors, S p o ns or, researc h 
staff, s u bjects, or t he pri mar y st u d y m o nit or. O nl y t he u n bli n de d st u d y p h ar macist(s) a n d t he 
u n bli n de d p har mac y  m o nit or will k n o w t he treat me nt assi g n me nt .  
T he f oll o wi n g st u d y pr o ce d ures will be i n place t o e ns ure d o u ble- bli n d a d mi nistrati o n of st u d y 
treat me nts: 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 3  of 9 8  
C o nfi de nti al  
•  
Access t o t he ra n d o mizati o n c o des will be strictl y c o ntr olle d via I R T. 
•  
T hr o u g h o ut t he st u d y, t h e bli n d s h o ul d re mai n u n br o ke n e x ce pt f or a n e mer ge nc y w h e n 
k n o wle d ge of t he s u bject’s st u d y me dicati o n is necessar y f or f urt her ma n a ge m e nt or if 
re q uire d f or re g ul at or y re p orti n g. T he Alla k os Me dical M o nit or a p pr o ves a n y e m er ge n c y 
bli n d brea k , if at all p ossi ble, pri or t o t he u n bli n di n g. 
•  
T he A K 0 0 2 a n d pl ace b o f or i nf usi o n will be i de ntical i n a p peara n ce , o nce pre pare d b y t he 
p har macist.  
•  
Res ults fr o m t he a nal ysis of bl o o d sa m ples f or P K  a n d A D A  will n ot be pr o vi de d t o t he 
I n v esti gat or a n d S p o ns or u ntil after data bas e l oc k.  
•  
Res ults fr o m t he a nal ysis of bl o o d sa m ples f or e x pl orat or y a nal ysis, e x pl orat or y safet y 
a nal ysis ( u nless i m me diatel y r e q uire d f or safet y iss ues) a n d a n y hista mi ne/tr y ptas e te sts 
will n ot be pr o vi de d t o t he I n vesti gat or a n d S p o ns or u ntil after data b ase l oc k.  
•  
After t he i nitial i nf usi o n of st u d y dr u g  a n d pri or t o e nr olli n g i n t he A K 0 0 2- 0 0 3 X e xte nsi o n 
st u d y (if a p plica ble), Da y 1 4 1 or Earl y Ter mi nati o n, res ults of t he assess me nts  n ote d bel o w 
will n ot be pr o vi de d t o t he I n vesti gat or a n d S p o ns or u ntil after data b ase l oc k . T he res ults 
will be re vie we d o n a n o n g oi n g basis b y a n u n bli n de d safet y m o nit or a n d escalate d as 
a p pr o priate.  
–  Differ e ntial cell c o u nt s (i ncl u di n g ne utr o p hils, e osi n o p hils, bas o p hils, m o n oc yt es, a n d 
l y m p h oc ytes).  
–  E n u merati o n of e osi n o p hils a n d  
 fr o m D a y 9 9 E G D bi o psies. 
Ot her t ha n u n der t he c o n diti o ns descri be d a b o ve, t he st u d y bli n d will be re v eale d o n c o m pleti o n 
of t he st u d y as n ote d i n Secti o n 1 6 . 
1 0. 4  Bre a ki n g t he Bli n d  
Brea ki n g t he bli n d i n a cli nical trial o n a n e mer ge n c y b asis b y t h e site s h o ul d o nl y occ ur w h e n 
k n o wle d ge of t he tr eat me nt t o w hic h a s u bject was all ocate d w o ul d ha v e i m plicati o ns f or t he 
e mer ge n c y me dical ma n a ge m e nt of t he s u bject or if re q uire d f or re g ul at or y re p orti n g. If 
necessar y, e mer ge nc y br ea ki n g of t he bli n d ca n b e c o n d ucte d t hr o u g h t h e I R T  b y re gistere d site 
users a n d/ or t he M e dical M o nit or. W he ne ver p ossi ble, t he I n vesti gat or s h o ul d c o ntact t he 
Me dic al M o nit or bef or e perf or mi n g a n e mer ge nc y brea k i n g of t he bli n d. Reas o n f or u n bli n di n g, 
pers o n c o n d ucti n g t he u n bli n di n g, pe rs o n(s) w h o k n o w t he u n bli n de d treat me nt, a n d date/ti me of 
u n bli n di n g will  be rec or d e d.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 4  of 9 8  
C o nfi de nti al  
1 1.  St u d y Pr oce d ures a n d G ui deli nes  
Ta ble 1  pr o vi des t he s c he d ule of e ve nts de pi cti 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 h e d ule d at t he s a me ti me p oi nt, t he pri orit y f or eac h will be as 
f oll o ws:  
•  
P R O Q uesti o n naire s h o ul d be c o m plete d b y  eac h s u bject  dail y (at a p pr o xi matel y t h e sa me 
ti me eac h e v e ni n g) d uri n g t he scree ni n g, treat me nt, a n d f oll o w- u p peri o ds. 
•  
 (self-a d mi nistere d f or mat) s h o ul d be c o m pl ete d at t he 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.   
•  
Vital si g ns will be o btai n e d after t he s u bject has b ee n at rest f or ≥5 mi n utes.  
•  
P h ysical e x a mi nati o ns 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 u ati o ns , u nless ot her wise s pecifie d.  
1 1. 1  Diet ar y  a n d Lif est yle Restric ti o ns 
S u bjects s h o ul d mai ntai n t he sa me diet a n d f o o d restricti o ns fr o m t he scree ni n g visit t hr o u g h t he 
E n d - of-St u d y v isit. C o m plia nce wit h pre vi o us dietar y a n d lifest yle restricti o ns will be ca pt ure d 
i n t he e C R Fs at eac h st u d y visit. 
1 1. 2  P h ar m a c o d y n a mi c/ Effic ac y -R el ate d Pr o ce d ures  
1 1. 2. 1  P R O Q uesti o n n aire  
A n electr o nic v ersi o n of t he P R O q uesti o n naire ( A p pe n di x 1 ) will be c o m plete d dail y e ver y 
e ve ni n g at a p pr o xi matel y t he sa me ti me b y t h e s u bject t hr o u g h o ut t he st u d y.  
S u bjects will n ot be 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 
n ot be a ble t o g o bac k a n d ma ke a n y c orrecti o ns or c ha n ges t o t he d ata ori gi nall y e ntere d. T his 
i nf or mati o n will be a ut o maticall y ca pt ure d a n d m ai ntai ne d in t he e P R O s yste m of t he E D C.  
A pa per v ersi o n of t he P R O q uesti o n naire is a vail a ble t o s u bjects i n case t h e y are n ot a ble t o 
c o m plete t he electr o nic v ersi o n f or a s h ort peri o d of ti me. O nl y o ne 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 matel y 2 4 h o urs l o n g. T his 
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 s u bjects ha v e a hist or y of c o nc o mita nt at o pic der matitis, at o pic ast h ma, or e osi n o p hilic 
es o p ha gitis, a n e xtra q ues ti o n will be p o p ulate d f or eac h rele v a nt c o n diti o n o n t he we bsite f or t he 
s u bject t o c o m plete dail y. A p a per v ersi o n of t hes e q uesti o ns ( A p pe n di x 9 ) is a vaila ble, s h o ul d 
t he we bsite n ot be accessi ble or t he s u bject n ot ha ve I nter n et access.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 5  of 9 8  
C o nfi de nti al  
1 1. 2. 2  
 
A pa per v ersi o n of t he 
 (A p p e n di x 2 ) will be c o m plete d b y t he s u bject at t he 
scree ni n g visit, pre- d os e o n i nf usi o n o n Da ys 1, 2 9 , 5 7, a n d 8 5, a n d o n f oll o w- u p Da ys 1 1 3 a n d 
1 4 1 ( or E T). T his i nf or m ati o n will be e ntere d i nt o t he E D C  b y t he st u d y sit e.  
1 1. 2. 3  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 Es o p ha g o- G astr o- D u o de n osc o p y ( E G D) wit h bi o ps y will be perf or me d d uri n g t he s cree ni n g 
peri o d a n d o n D a y 9 9 ( ± 3 da ys). 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 ntral La b ( or desi g nee) f or fi xi n g a n d stai ni n g. A bli n de d 
Ce ntral rea d er will re p ort, a m o n g ot her t hi n gs, ma xi m u m n u m ber of e osi n o p hils per H P F , 
ma xi m u m n u m ber of tr y pta se-p ositi ve mast cells per H P F , a n d gastric bi o psies will be gra de d 
usi n g t he S y d ne y S yst e m o n i nfla m mati o n, meta plasia, atr o p h y, a n d reacti ve gastr o pat h y.  T he 
Mars h Scale Classific ati o n will be use d t o gra de d u o de nal sa m ples.  
D uri n g t h e c o n d uct of t h e E G D, a n atte n di n g practitio ner will assess  a n d gra de vari o us as pects of 
t he GI tract, acc or di n g t o t he 
 
(A p pe n di x 7 ).  
Da y 9 9 E G D r es ults will n ot be pr o vi de d t o t he I n vesti gat or a n d S p o ns or u ntil after data bas e 
l oc k. A n u n bli n de d Safet y M o nit or will re vie w t h e E G D res ults a n d re p ort a n y iss ues f or 
escalati o n t o t he Me dical M o nit or a n d t he cli nical site, as a p pr o priat e, w hile mai ntai ni n g t he 
bli n d. 
T he scree ni n g E G D will be use d t o deter mi ne t h e f oll o wi n g I n cl usi o n/ E x cl usi o n criteria , a n d t he 
res ults m ust be a vaila ble fr o m t he Ce ntral rea der b ef ore t h e s u bject’s eli gi bilit y ca n b e verifie d. 
•  
I n cl usi o n # 3: E osi n o p hilia of t he gastric m u c osae ≥3 0 e osi n o p hils/ H P F  i n 5 H P F s or of t he 
d u o de nal m uc osa ≥3 0 e osi n o p hils/ H P F i n 3  H P F s fr o m t he E G D p erf or m e d d uri n g t he 
scree ni n g p eri o d, wit h o ut a n y ot h er ca use f or t he gastric / d u o de nal e osi n o p hilia. 
•  
E x cl usi o n # 2 : Dia g n osis of celiac dis ease or acti v e H. pyl ori *  i nfecti o n as deter mi ne d b y 
scree ni n g E G D or a hist or y or celiac diseas e dia g n ose d b y  pri or E G D.  
*   
A dia g n osis of acti ve H.  pyl ori at scree ni n g ma y b e treate d wit h sta n dar d t h era pies a n d 
as l o n g as c o nfir me d n e gati ve pri or t o e nr oll me nt a n d s y m pt o ms re mai n sta ble,  t he 
s u bject ma y b e ra n d o mize d i nt o t he st u d y.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 6  of 9 8  
C o nfi de nti al  
1 1. 2. 4  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 o m plete bl o o d c o u nt ( C B C) wit h differe ntial at t he scree ni n g visit, as 
well as pre - d os e a n d 1- h o ur p ost- d ose o n Da ys 1, 2 9,  5 7, a n d 8 5, a n d o n f oll o w- u p Da ys 4, 1 5, 
9 9, 1 1 3, 1 4 1 ( or E T), as well as d uri n g t he E xte n de d F oll o w- U p p eri o d, if a p pr o priate. O n 
I nf usi o n Da y 1, a bl o o d s a m ple will als o be c ollect e d 4 h o urs aft er t he e n d of t he i nf usi o n. T he 
bl o o d sa m ple will be pr ocesse d a n d s hi p p e d i n acc or da nce wit h la b orat or y ma n ual a n d la b kit 
i nstr ucti o ns. A ce ntral la b orat or y will a nal yz e t he bl o o d sa m ple a n d pr o vi d e res ults f or C B C wit h 
differe nt ial, i ncl u di n g he m o gl o bi n, he mat ocrit, pl atelet 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 ntial c o u nt ( ne utr o p hils, l y m p h oc yt es, m o n oc yt es, e osi n o p hils, 
bas o p hils). 
T he Da y 4 bl o o d sa m ple ma y b e c ollecte d o n site, or t he s u bject ma y be s e nt h o me wit h a 
Ce ntral la b he mat ol o g y c ollecti o n kit , s hi p pi n g la bel, a n d la b orat or y re q uisiti o n. If t he s a m ple is 
n ot c ollecte d o n site, t he s u bject ma y g o t o a l ocal la b or ha ve a visit fr o m a h o me n urse t o 
c ollect this sa m ple, t o be se nt t o t he Ce ntral la b f or a nal ysis. T h e differe ntial he mat ol o g y res ults 
m ust re mai n bli n de d.  
T he bl o o d differ e ntial test res ults ( ne utr o p hils, e osi n o p hils, bas o p hils, m o n oc yt es, a n d 
l y m p h oc ytes) will be bli n de d fr o m t he I n v esti gat or a n d S p o ns or fr o m p ost- d ose Da y 1 a n d pri or 
t o Da y 1 4 1 or Earl y T er mi nati o n, u ntil data base l oc k has occ urre d. As des cri be d i n t he 
I n v esti gat or’s Br oc h ure, t hese ar e part of t h e e x pecte d effects of A K 0 0 2 a n d c o ul d p ote ntiall y 
ser ve t o u n bli n d bli n de d me m bers of t he st u d y. A n u n bli n de d S afet y M o nit or will ha ve real- ti me 
access t o t hese la b or at or y r es ults a n d will re vie w a n d escal ate a n y c o ncer ns/iss ues t o t he Me dical 
M o nit or a n d/ or t he site as a p pr o priate. A n u nsc he d ule d C B C , wit h differe ntial ma y be c ollecte d 
if re q ueste d b y t he Safet y Mo nit or. All pa nic alerts f or bli n de d val ues will b e se nt t o t he 
u n bli n de d Safet y M o nit or a n d e val u ate d i n real  ti me. 
Da y 1 4 1 or Earl y Ter mi n ati o n bl o o d differe ntial res ults will n ot be bli n de d i n or der t o all o w f or 
c o nfir mati o n  of e osi n o p hil a n d l y m p h oc yte rec o v er y a n d t o i de ntif y t h ose s u bjects t hat nee d t o 
e nter t he E xte n de d F oll o w- U p peri o d.  
1 1. 2. 5  B aseli ne Diet  Assess me nt  
D uri n g t h e scr ee ni n g visit t he I n v est i gat or or desi g nee will as k t he s u bject a sta n dar dize d series 
of dietar y ass ess me nt q uesti o ns ( A p pe n di x 3 ). T his Baseli ne Diet  Ass ess me nt i n v ol ves q uesti o ns 
re gar di n g f o o d be ha vi or a n d patter ns, as well as t y p es of f o o ds ge n erall y a v oi de d , a n d will ser ve 
t o esta blis h t he b aseli ne d iet. A ns wers will be d oc u me nte d i n t he s o urce d o c u me nts a n d rec or de d 
i n t he e C R F. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 7  of 9 8  
C o nfi de nti al  
T his b aseli 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 o ut t he c o urse of t he st u d y, 
e ve n if s y m pt o ms i m pr o ve.  
C o m plia nce wit h t he b as eli ne d iet will be assesse d at e ver y st u d y visit, o n Da ys 1, 1 5, 2 9, 5 7, 8 5, 
9 9, 1 1 3, a n d 1 4 1 ( or E T). W het her or n ot t he s u bject has mai ntai ne d t he b as eli ne diet a n d if n ot, 
w hat de viati o ns wer e ma de, s h o ul d be d oc u me nte d i n t he s o urce a n d t h e e C R F.  
1 1. 2. 6  
 
I n ass ociati o n wit h t he c o n d uct of t he E G D  d uri n g t he scree ni n g p eri o d a n d o n Da y 9 9 ( or E T), 
t he atte n di n g p h ysici a n will assess a n d gra d e vari o us  
, 
acc or di n g t o t he 
. See A p pe n di x 7 . 
1 1. 3  S af et y -Rel ate d Pr o ce d ures  
1 1. 3. 1  C o nc o mit a nt Me dic ati o ns  
All c o nc o mita nt me dicati o n a n d c o nc urre nt t hera pies will be  d oc u me nte d at scree ni n g a n d at 
st u d y visits, if c ha n ges ar e ma de. D ose, r o ute, u nit, fre q ue n c y of a d mi nistrati 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 ure d. A n y pri or me dicati o n recei ve d wit hi n 
3 0 da ys b ef or e s cr ee ni n g a n d d uri n g t he st u d y t hr o u g h Da y 1 4 1 ( or E T) will be rec or de d.  
1 1. 3. 2  C o m plete P h ysic al E x a mi n ati o n 
A c o m plete p h ysical e x a m will be perf or me d b y eit her t he I n vesti gat or or a q ualifie d 
S u bi n vesti gat or d uri n g t h e s cree ni n g visit . A c o m plete p h ysical e x a m will i ncl u de t he f oll o wi n g 
b o d y s yste m or or ga n ass ess me nts: s ki n; hea d, e yes, ears, n ose, a n d t hr oat ( H E E N T); t h yr oi d; 
l u n gs; car di o vasc ular; a b d o me n; e xtre mities; l y m p h n o des; a n d a brief ne ur ol o gical e x a mi nati o n.  
1 1. 3. 3  B o d y Wei g ht a n d H ei g ht 
At scree ni n g, h ei g ht i n c m a n d wei g ht i n k g will be meas ure d a n d b o d y m ass i n de x ( B MI) will 
be calc ul ate d. O n D a y s 1, 2 9, 5 7, a n d 8 5 o nl y, w ei g ht will be calc ulate 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 a d mi nistere d. B o d y wei g ht will b e e ntere d i n t o t he I R T 
f or eac h d osi n g visit a n d will als o be rec or d e d o n t he I P D ose Calc ulati o n a n d Pre parati o n 
W or ks heet ( U N B LI N DI N G) t hat t he u n bli n de d p har macist will mai ntai n a n d d oc u me nt f or eac h 
s u bject’s d ose calc ulati o ns. B o d y wei g ht s h o ul d b e c ollecte d o n site o n t he da y of eac h st u d y 
dr u g i nf usi o n, or 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 y s 1 5, 1 1 3, a n d 1 4 1 or E T.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 4 8  of 9 8  
C o nfi de nti al  
1 1. 3. 4  St o ol S a m ple f or O v a a n d P ar asite 
At scree ni n g, fecal c ollecti o n kits will be pr o vi de d t o s u bjects f or t he O va a n d Parasite test. 
S u bjects  will ret ur n t he sa m ple t o t he site d uri n g t he scree ni n g peri o d, wit hi n 1 da y of c ollecti o n. 
T he site will s hi p sa m ples t o a ce ntral la b orat or y w here t he y will be teste d f or t he pres e nce of 
O va a n d/ or Pa r asites. A ne gati ve res ult f or hel mi nt hic parasites m ust be o btai ne d fr o m t he 
ce ntral la b orat or y pri or t o ra n d o mizati o n i nt o t he st u d y ( D a y 1). Hist oric la b res ults s h o wi n g 
ne gati ve hel mi nt hic i nfecti o ns fr o m 9 0 da ys pri or t o scree ni n g ma y b e use d t o satisf y t his 
criterio n, at t he discreti o n of t he I n vesti gat or.  
1 1. 3. 5  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- directe d p h ysical e x a m , a n e x a mi nati o n of re p orte d or o bser v e d s u bject s y m pt o ms 
warr a nti n g e x a mi nati o n (i n t he o pi ni o n of t he I n v esti gat or) i ncl u di n g ass ess me nts of p ossi ble 
i nf usi o n site reacti o ns a n d I R Rs, will be perf or me d b y eit her t he I n v esti gat or or a q ualifie d 
S u bi n vesti gat or at all st u d y visits d uri n g t he treat me nt peri o d a n d f oll o w- u p p eri o d. Ne w , 
a b n or mal p h ysical e x a m  fi n di n gs m ust be d oc u me nte d a n d will be f oll o we d b y t he st u d y d oct or 
or S u bi n vesti gat or at t he ne xt sc he d ule d visit or s o o n er 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. 6  Electr oc a r di o gr a m  
A n E C G will be o btai ne d d uri n g s cree ni n g after t h e s u bject  has bee n i n t he s u pi ne p ositi o n f or 
≥5  mi n utes a n d bef ore a n y bl o o d dr a w. T he I n vesti gat or or S u bin vesti gat or will re vie w a n d 
assess a n y a b n or malities o n t he E C G  i n ter ms of cli nical si g nifica n ce. T h e E C G ( wit h o ut 
i nte nsi ve Q T a nal ysis) will be use d t o i de ntif y dis eases or c o n diti o ns t hat w o ul d p ut t he s u bject 
at i ncreas e d ris k if partici pati n g i n a cli nical trial , s o t his s h o ul d be ta ke n i nt o c o nsi derati o n w he n 
e val uati n g eli gi bilit y f or e ntr y i nt o t he st u d y.  
1 1. 3. 7  Vit al Si g ns  
Vital si g ns, i ncl u di n g s u pi ne 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 r ate, will be t a ke n aft er t he s u bject has bee n at rest  f or ≥5 mi n utes a n d bef ore a n y 
bl o o d dra w ( e x ce 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 b el o w).  
O n d osi n g da ys, vital si g ns will be meas ure d pre- d ose, 1 5 mi n u tes ( ± 5 mi n utes ) after t he start o f 
i nf usi o n, i m me diatel y f oll o wi n g t he e n d of i nf usi o n ( + 5 mi n utes ), 1 h o ur ( ± 1 5 mi n utes ) i nt o t he 
o bser vati o n peri o d a n d j ust pri or t o disc har ge . Please refer t o t he sc h e d ule of e ve nts i n Ta ble 1 . 
1 1. 4  Cli nic al L a b or at or y Me as ure me nts  
Bl o o d a n d uri ne s a m ples f or cli nical safet y la b orat or y tests will be c ollecte d at t he ti me p oi nts 
descri be d b el o w a n d i n T a ble 1 . I n vesti gat ors ma y ha ve a d diti o nal la b orat or y tests p erf or m e d f or 


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t he p ur p ose of pla n ni n g treat me nt a d mi nistrati o n or f oll o wi n g a d vers e e ve nts or a b n or mal la b 
val ues.  
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 ntral la b orat or y i nstr ucti o ns. A 
ce ntral la b orat or y or d esi g nee will a nal yz e 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 
f oll o wi n g cli nical s afet y la b orat or y tests ( Secti o ns 1 1. 4. 1 – 1 1. 5. 6 ). 
F or a n y l a b orat or y test v al ue o utsi de t he refere nce ra n ge t h at t he I n vesti gat or c o nsi ders c li 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 v al ue. 
•  
F oll o w t he 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 st art 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 gni fica nt  
–  R e 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 ui res a patie nt t o r ecei ve treat me 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 ntial as descri be d i n Secti o n 1 1. 2. 4 . 
1 1. 5  Bl o o d C he mistr y Pr ofile 
Bl o o d will be o btai ne d f or c he mistr y tests at scree ni n g a n d pre - d os e o n d osi n g Da ys 1, 2 9, 5 7, 
a n d 8 5, as well as D a ys 1 5, 1 1 3, a n d 1 4 1 or E/ T. 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 d a nce wit h 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 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 res ults f or c h e 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 nat e, gl uc ose, bl o o d urea nitr o ge n, creati ni ne, creati ne 
ki nase, calci u m, p h os p h or us, ma g n esi 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 nsferas e  ( A S T), ala ni n e a mi n otra nsferase ( A L T), al k ali ne p h os p hatase, 
ga m ma -gl uta m yl tr a nsfer ase  ( G G T), a n d lactate d e h y dr o ge nas e. 
1 1. 5. 1  Pre g n a nc y Test  a n d F ollicle - Sti m ul ati n g H or m o ne 
A ser u m pre g n a nc y test will be o btai ned f or all fe male s u bjects of c hil d beari n g p ote ntial. 
W o me n w h o are s ur gicall y sterile (t u b al 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 us al f or at least 1 year wi t h F S H le vel > 4 0 mI U/ m L 
are n ot c o nsi dere d t o be of c hil d beari n g p ote ntial . At scree ni n g, F S H will be teste d o n fe m ale 
su bjects  t o c o nfir m p ost- me n o pa usal stat us. B ot h  sa m ples will be pr ocesse d b y t he Ce ntral 
L a b orat or y.  


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O n Da ys 1, 2 9, 5 7, a n d 8 5  ( pri or t o eac h d ose), a n d at Da y 14 1 or E T, pre -me n o pa usal fe m ales 
(scree ni n g F S H le v el ≤4 0 mI U/ m L) will pr o vi de a uri ne sa m ple f or pre g n a nc y ( h C G) testi n g. 
T he site will perf or m a uri ne pre g n a nc y h C G test usi n g a n i n dicat or stic k fr o m t he pre g na nc y t est 
kit s u p pli e d b y t h e ce ntral la b orat or y. T his test is t o be assesse d b y t he st u d y staff pri or t o t he 
start of eac h st u d y dr u g i nf usi o n. 
1 1. 5. 2  Uri n al ysis  
Uri ne will be o btai ne d f or uri nal ysis at scree ni n g a n d o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, a n d 1 4 1 ( or 
E T). T he uri ne s a m ple will be pr ocesse d a n d s hi p pe d i n acc or da nce wit h t he la b orat or y m a n ual 
a n d la borat or y kit i nstr ucti o ns. A ce ntral la b orat or y will a nal yze t he uri n e s a m ple f or s pecific 
gr a vit y, p H, pr otei n, gl uc ose, ket o nes, bl o o d, a n d l e u k oc yte esterase.  
1 1. 5. 3  Ser ol o g y 
Bl o o d will be o btai ne d at s cree ni n g f or ser ol o g y tests i ncl u di n g he patitis B s urface a nti ge n 
( H bs A G), h e patitis C a nti b o d y, he p atitis B c ore a nti b o d y (a nti- H Bc), a n d h u ma n 
i m m u n o deficie nc y vir us ( HI V). T h e bl o o d sa m ple will be pr ocesse d a n d s hi p pe d t o t he ce ntral 
la b orat or y i n acc or d a nce wit h la b orat or y ma n ual a n d la b kit i nstr ucti o ns. A p ositi ve res ult, if 
cli nicall y si g nifica nt  (a n d n ot d ue t o pre vi o us vacci nati o n) w o ul d e x cl u de t he s u bject fr o m 
e nr oll me nt.  
1 1. 5. 4  A nti - A K 0 0 2 Anti b o dies  
Bl o o d will be c ollecte d f or deter mi nati o n of A D A at scree ni n g, o n Da y s 1 5, 2 9, 5 7, 8 5 a n d o n 
Da y 1 4 1 ( or E T), a n d a n u nsc he d ule d bl o o d sa m pl e f or A D A ma y als o be o btai ne d if a relate d 
A E s us pecte d of b ei n g ass ociate d wit h i m m u n o ge nicit y occ urs. T he s er u m sa m ple will be 
pr ocesse d a n d s hi p pe d i n acc or d a nce wit h t he la b orat or y ma n ual a n d la b kit i nstr ucti o ns. A 
ce ntral la b orat or y will a n al yze t he sa m ple f or a nti - A K 0 0 2 a nti b o dies usi n g a vali date d ass a y 
met h o d. 
1 1. 5. 5  Bl o o d f or P h ar m a c o ki netics a n d St or a ge 
Bl o o d sa m p les f or s er u m P K assess me nts will be c ollecte d d uri n g t he s cree ni n g p eri o d as w ell as 
pre - d ose o n d osi n g D a ys 2 9, 5 7, a n d 8 5 a n d f oll o w- u p Da ys 1 5, 1 1 3, a n d 14 1 or E T. T he ser u m 
sa m ples will be pr ocesse d a n d s hi p pe d fr oze n i n acc or da n ce wit h t he st u d y la b orat or y ma n u al 
a n d la b orat or y kit i nstr ucti o ns.  
A K 0 0 2 c o nce ntrati o ns will be deter mi ne d b y t he ce ntral la b orat or y or desi g nee usi n g a vali date d  
E LI S A m et 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 be pr o vi de d i n t he ce ntral la b orat or y ma n u al .  


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1 1. 5. 6  Bl o o d f or E x pl or at or y A n al ysis 
Bl o o d sa m ples f or e x pl orat or y a nal ysis will be c ollecte d pre- d ose o n D a ys 1, 2 9, a n d 8 5 a n d als o 
o n D a y 1 4 1 or E T . T h e s er u m sa m ples will be pr o cesse d a n d s hi p p e d fr oze n i n acc or d a nce wit h 
t he st u d y la b or at or y ma n ual a n d la b orat or y kit i nstr ucti o ns.  
1 1. 5. 7  Bl o o d f or E x pl or at or y S af et y A n al ysis, h ist a mi ne a n d tr y pt ase 
If a na p h yl a 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 pl as ma hista mi ne le vel a n d 
tr y ptas e wit hi n 1– 2 h o urs of t he o nset of t he s y m pt o ms. T he sa m ple will be se nt t o t he ce ntral la b 
f or pr ocessi n g. If t he s u bject e x perie nces a n I R R t hat ca uses a n i nterr u pti o n or cessati o n of t he 
st u d y dr u g i nf usi o n a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of 
s y m pt o ms, f or e x pl orat or y safet y a n al ysis. 
1 1. 5. 8  A d diti o n al S a m ples f or Bi o m ar ker S u b-St u d y  
At selecte d st u d y sites, a d diti o nal sa m ples ( bl o o d, uri ne, a n d bi o ps y) will be c ollecte d f or a s u b-
st u d y t o e val uat e bi o mar kers. See A p p e n di x 8 . 
1 2.  E v al u ati o ns a n d Pr oce d ures b y Visit 
E val uati o ns a n d pr oce d ur es b y visit ar e s h o w n i n Ta ble 1 . 
Ge ner al I nf or m ati o n : 
•  
All rec or d e d cl oc k ti mes s h o ul d utilize a 2 4- h o ur cl oc k. 
•  
Da y 1 is t he da y of t he first i nf usi o n. 
•  
Pr oce d ures f or scree ni n g ma y b e perf or me d o ver t he c o urse of m ulti ple vi sits pri or t o first 
i nf usi o n. 
1 2. 1  Scree ni n g  Peri o d  
1)  
O btai n writte n i nf or me d c o nse nt. 
2) 
Assi g n t he partici pa nt a Patie nt I D N u m ber  ( PI D). 
3)  
Be gi n t he c ollecti o n of seri o us a d verse e ve nts relat e d t o a n y s cree ni n g acti vities . 
4) 
C ollect de m o gr a p hics a n d me dical hist or y . 
5)  
Rec or d pri or a n d c o nc o mita nt me dicati o ns. 
6)  
Deter mi ne b o d y w ei g ht a n d hei g ht. 
7) 
 t o b e c o m plete d b y t he s u bject. 
8) 
Perf or m Baseli ne D iet Assess me nt. 


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9)  
O btai n vital si g ns bef ore bl o o d dra ws. 
1 0) Perf or m a c o m plet e p h ysical e x a mi nati o n . 
1 1)  O btai n a 1 2-lea d E C G bef ore bl o o d dra w. 
1 2) C ollect t he f oll o wi n g sa m ples  f or t he ce ntral la b orat or y: 
a)  Ser u m pre g na n c y test a n d F S H (if s u bject of c hil d beari n g p ote ntial or p ost- me n o pa usal) 
b)  C B C wit h differe ntial  
c)  C he mistr y  
d)  Uri nal ysis  
e)  Bl o o d f or A nti - A K 0 0 2 a nti b o d y 
f) Bl o o d f or Ser ol o g y testi n g 
g)  Bl o o d f or P K a n d st or a ge 
1 3)  Pr o vi de s u b ject a st o ol c ollecti o n kit a n d as k t he m t o ret ur n it t o t he site wit hi n 1 da y of 
c ollecti o n (u nless s u bject ca n  pr o vi de s a m ple w hile o n site). 
1 4) Acti vate s u bject access t o dail y E G  a n d/ or E G E P R O q uesti o n naire a n d i nstr uct s u bject o n 
use of t he q uesti o n nair e.  
1 5) Perf or m  a S cr ee ni n g/ B as eli ne Es o p ha g o- G astr o- D u o de n osc o p y ( E G D) wit h bi o ps y 
f oll o wi n g pr o ce d ur es pr o vi de d b y Alla k os. Assess a n d gra de 
 usi n g 
t he 
.  
1 6) Usi n g res ults fr o m t he Ce ntral Hist ol o g y Rea der , co nfir m t he e osi n o p hil c o u nt fr o m t he 
gastri c  a n d/ or d u o de n al bi o psies q ualif y t he s u bject f or t he st u d y, a n d t here are n o 
e x cl usi o nar y criteria f o u n d o n t he E G D. 
1 2. 2  D a y  1 – D a y of First Inf usi o n  
1)  
Pri or t o t he i nf usi o n: 
a)  Assess t he s u bject f or S A Es  relate d t o scree ni n g pr oce d ures  
b)  C o nfir m c o nti n ui n g eli gi bilit y 
c)  D oc u me nt a n y c h a n ges t o healt h stat us  
d)  D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns  
e)  D oc u me nt a n y c h a n ges t o baseli ne diet  
f) 
 
g)  Deter mi ne b o d y w ei g ht  


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h)  Perf or m uri ne pre g na n c y test  (if s u bject is of c hil d beari n g p ote ntial) 
i) C ollect vital si g ns  
j) Perf or m s y m pt o m -dir ect e d p h ysical e x a m, as nee de d  
k)  C B C wit h differe ntial  
l) C he mistr y  
m)  Uri nal ysis  
n)  Bl o o d f or T otal S er u m I g E 
o)  Bl o o d f or E x pl orat or y a n al ysis 
p)  C etirizi ne 1 0  m g a n d aceta mi n o p he n 1 0 0 0 m g ( or a p pr o ve d alter nati ve) will be 
a d mi nistere d  as pr e me dicati o n a p pr o xi matel y 1 h o ur bef ore d osi n g 
2)  
Pri or t o ra n d o mizi n g t he s u bject i n t he I R T s yste m, t he site will i de ntif y t he hi g hest w ee kl y 
a vera ge sc or e r ec or d e d f or a n y of t he f oll o wi n g s y m pt o ms of disease d uri n g at least 
2 wee ks  of P R Os : a b d o mi nal pai n, na usea , a n d/ or diarr hea . T he st u d y c o or di nat or or 
desi g nee will e nter t h e hi g hest a v era ge q ualif yi n g sc ore i nt o t he I R T o n St u d y D a y 1 t o 
stratif y t he s u bj ect, as w ell as b o d y w ei g ht a n d PI D.  
3)  
O nce t he s u bject has bee n ra n d o mize d i n t he I R T s yste m, t he u n bli n de d p h ar macist will 
recei v e a n e m ail wit h PI D, b o d y w ei g ht, treat me nt assi g n me nt, a n d kit n u m ber.  
4)  
T he u n bli n de d st u d y p h ar macist will pr e pare st u d y dr u g usi n g t he w ei g ht o btai ne d at t he 
visit . T he f i 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 cal c ulate d d ose of st u d y dr u g will be a d mi nistere d t o t he  s u bject. 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 he I V li ne 
at t he be dsi de or t o be l eft o ver i n t he i nf usi o n ba g. 
5)  I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o v er at least 5 h o urs usi n g a n i nf usi o n p u m p. See 
P har mac y Ma n u al 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. 
b)  C ollect vital si g ns 1 5 ( ±5) mi n utes after t he start of i nf usi o n . 
c)  If t he s u bject e x perie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y 
dr u g i nf usi o n a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of 
s y m pt o ms, f or e x pl orat or y safet y a n al ysis. If a na p h yla xis is s us pecte d, a sa m ple of 
bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne le v el a n d tr y ptase wit hi n 1 – 2 h o urs of 
t he o nset of t he s y m pt o ms. Als o, 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- relat e d A E is s us pecte d. 


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6)  
P ost-i nf usi o n: 
a)  C ollect vital si g ns i m me diatel y f oll o wi n g ( + 5 mi n utes) t he e n d of i nf usi o n. 
b)  C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n. C ollect 
vital si g ns 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n, as well as i m me diatel y 
pri or t o disc har ge h o m e. 
c)  C ollect C B C wit h differe ntial 4 h o urs ( ± 1 5 mi n utes) after t h e e n d of t he i nf usi o n. 
d)  O bser ve t h e p atie nt f or at least 4 h o urs after t he e n d of i nf usi o n. 
1 2. 3  D a y 4 ( ± 1) 
1) 
C B C wit h differe ntial.  
1 2. 4  D a y  1 5 ( ± 2) 
1) 
Assess t he s u bject f or A Es  a n d S A Es.  
2) 
D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns . 
3) 
D oc u me nt a n y c h a n ges t o baseli ne diet . 
4) 
C ollect vital si g ns . 
5) 
Perf or m s y m pt o m -dir ect e d P E, as nee d e d . 
6) 
C B C wit h differe ntial . 
7) 
C he mistr y . 
8)  
Bl o o d f or A nti - A K 0 0 2 a nti b o d y. 
9)  
Bl o o d f or P K a n d st or a ge. 
1 2. 5  D a y 2 9 ( ± 3 ) – D a y of Sec o n d I nf usi o n 
1)  
Pri or t o t he i nf usi o n: 
a)  Assess t he s u bject f or A Es  a n d S A Es 
b)  D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns  
c)  D oc u me nt a n y c h a n ges t o baseli ne diet  
d)  
 
e)  Deter mi ne b o d y w ei g ht  
f) Perf or m uri ne pre g na n c y test  (if s u bject is of c hil d beari n g p ote ntial) 
g)  C ollect vital si g ns  


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h)  Perf or m s y m pt o m -dir ect e d p h ysical e x a m, as nee de d  
i) C B C wit h differe ntial  
j) C he mistr y  
k)  Uri nal ysis  
l) Bl o o d f or P K a n d st or a ge 
m)  Bl o o d f or A D A 
n)  Bl o o d f or E x pl orat or y a n al ysis 
o)  C etirizi ne 1 0  m g a n d aceta mi n o p he n 1 0 0 0 m g or a p pr o ve d alter nati ve will  be 
a d mi nistere d as pr e me dicati o n a p pr o xi matel y 1 h o ur bef ore d osi n g. 
p)  T he I R T will be accesse d, a n d t he s u bject’s PI D  a n d b o d y w ei g ht will be e ntere d . O nl y 
t he u n bli n de d st u d y p har macist will recei ve t he treat me nt assi g n me nt a n d kit n u m ber 
f or t he s u bject. 
2)  
T he u n bli n de d st u d y p h ar macist will pre pare st u d y dr u g usi n g t he c urre nt wei g ht o btai n e d . 
3)  I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o v er at least 4 h o urs usi n g a n i nf usi o n p u m p. See 
P har mac y Ma n u al 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. 
b)  C ollect vital si g ns 1 5 ( ±5) mi n utes after t he start of i nf usi o n . 
c)  If t he s u bject e x perie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y 
dr u g i nf usi o n a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of 
s y m pt o ms, f or e x pl orat or y safet y a n al ysis. If a na p h yla xis is s us pecte d, a sa m ple of 
bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne le v el a n d tr y ptase wit hi n 1 – 2 h o urs of 
t he o nset of t he s y m pt o ms. Als o, 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- relat e d A E is s us pecte d. 
4)  
P ost-i nf usi o n: 
a)  C ollect vital si g ns i m me diat el y f oll o wi n g ( + 5 mi n utes) t he e n d of i nf usi o n. 
b)  C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n.  
c)  O bser ve t he s u bj ect f or 4 h o urs after t h e e n d of t h e i nf usi o n. 
d)  C ollect vital si g ns 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t he i nf usi o n, as well as 
i m me diatel y pri or t o disc har ge h o me. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 5 6  of 9 8  
C o nfi de nti al  
1 2. 6  D a y  5 7 ( ± 3) – D a y of T hir d I nf usi o n 
1)  
Pri or t o t he i nf usi o n: 
a)  Assess t he s u bject f or A Es a n d S A Es . 
b)  D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns . 
c)  D oc u me nt a n y c h a n ges t o baseli ne diet . 
d)  
. 
e)  Deter mi ne b o d y w ei g ht . 
f) Perf or m uri ne pre g na n c y test  (if s u bject is of c hil d beari n g p ote ntial). 
g)  C ollect vital si g ns . 
h)  Perf or m s y m pt o m -dir ect e d P E, as nee d e d . 
i) C B C wit h differe ntial . 
j) C he mistr y . 
k)  Uri nal ysis . 
l) Bl o o d f or P K a n d st or a ge. 
m)  Bl o o d f or A D A. 
n)  C etirizi ne 1 0  m g a n d aceta mi n o p he n 1 0 0 0 m g or a p pr o ve d alter nati ve ma y  be 
a d mi nistere d as pr e me dicati o n a p pr o xi matel y 1 h o ur bef ore d osi n g, at t he discreti o n of 
t he I n v esti gat or or S u b-i n vesti gat or a n d de p e n di n g o n t olera nce t o pri or i nf usi o ns. 
2) 
T he I R T will be accesse d, a n d t he s u bject’s PI D a n d wei g ht will be e ntere d . O nl y t he 
u n bli n de d st u d y p har m acist will recei ve t he treat me nt assi g n me nt f or t he s u bject. 
3)  
T he u n bli n de d st u d y p h ar macist will pre pare st u d y dr u g usi n g t he w ei g ht o btai ne d at t he 
visit .  
4)  I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o v er at least 4 h o urs usi n g a n i nf usi o n p u m p. See 
P har mac y Ma n u al 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. 
b)  C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of i nf usi o n . 
c)  If t he s u bject e x perie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y 
dr u g i nf usi o n a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of 
s y m pt o ms, f or e x pl orat or y safet y a n al ysis. If a na p h yla xis is s us pecte d, a sa m ple of 
bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne le v el a n d tr y ptase wit hi n 1 – 2 h o urs of 
t he o nset of t he s y m pt o ms. Als o, 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- relat e d A E is s us pecte d. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 5 7  of 9 8  
C o nfi de nti al  
5)  
P ost-i nf usi o n: 
a)  C ollect vital si g ns i m me diatel y f oll o wi n g ( + 5 mi n utes) t he e n d of i nf usi o n.  
b)  C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n.  
c)  O bser ve t he s u bj ect f or 2 – 4 h o urs after t h e e n d of t he i nf usi o n, at t he I n vesti gat or’s 
discreti o n a n d de p e n di n g o n t olera nce t o pri or i nf usi o ns. 
d)  C ollect vital si g ns 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t he i nf usi o n, as well as 
i m me diatel y pri or t o disc har ge h o me. 
1 2. 7  D a y 8 5 ( ± 3) – D a y of F o urt h I nf usi o n 
1)  
Pri or t o t he i nf usi o n: 
a)  Assess t he s u bject f or A Es a n d S A Es . 
b)  D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns . 
c)  D oc u me nt a n y c h a n ges t o baseli ne diet  
d)  
. 
e)  Deter mi ne b o d y w ei g ht . 
f) Perf or m uri ne pre g na n c y test (if s u bject is of c hil d beari n g p ote ntial) . 
g)  C ollect vital si g ns . 
h)  Perf or m s y m pt o m -dir ect e d P E, as nee d e d . 
i) C B C wit h differe ntial . 
j) C he mistr y . 
k)  Uri nal ysis . 
l) Bl o o d f or P K a n d st or a ge. 
m)  Bl o o d f or A D A. 
n)  Bl o o d f or E x pl orat or y a n al ysis. 
o)  C etirizi ne 1 0  m g a n d aceta mi n o p he n 1 0 0 0 m g or a p pr o ve d alter nati ve ma y  be 
a d mi nistere d as pr e me dicati o n a p pr o xi matel y 1 h o ur bef ore d osi n g, at t he discreti o n of 
t he I n v esti gat or or S u bi n vesti gat or a n d de p e n di n g o n t olera nce t o pri or  i nf usi o ns. 
2) 
T he I R T  will be accesse d, a n d t he s u bject’s PI D a n d b o d y w ei g ht will be e ntere d. O nl y t he 
u n bli n de d st u d y p har m acist will recei ve t he treat me nt assi g n me nt a n d kit n u m ber f or t he 
s u bject. 
3)  
T he u n bli n de d st u d y p h ar macist will pre pare st u d y dr u g usi n g t he c urre nt wei g ht o btai n e d . 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 5 8  of 9 8  
C o nfi de nti al  
4)  I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o v er 3 – 5 h o urs usi n g a n i nf usi o n p u m p. See 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. 
b)  C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of i nf usi o n.  
c)  If a na p h yl a xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas m a hista mi ne 
le vel a n d tr y ptase wit hi n 1– 2 h o urs of t he o nset of t he s y m pt o ms. Als o, 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 ni cit y- relate d A E is s us pecte d. If 
t he s u bject e x perie nces a n I R R t hat ca us es a n i nterr u pti o n or cess ati o n of t he st u d y dr u g 
i nf usi o n a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of s y m pt o ms, 
f or e x pl orat or y saf et y a n al ysis.  
5)  
P ost-i nf usi o n: 
a)  C ollect vital si g ns i m me diatel y f oll o wi n g ( + 5 mi n utes) t he e n d of i nf usi o n.  
b)  C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n. 
c)  O bser ve t he s u bj ect f or 2 – 4 h o urs after t h e e n d of t he i nf usi o n, at t he I n vesti gat or’s 
discreti o n a n d de p e n di n g o n t olera nce t o pri or i nf usi o ns. 
d)  C ollect vital si g ns 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t he i nf usi o n, as well as 
i m me diatel y pri or t o disc har ge h o me. 
1 2. 8  D a y 9 9 ( ± 3) 
1)  
S u bject s h o ul d arri v e f asti n g f or t h e E G D pr o ce 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. 
2) 
C ollect A Es, S A Es, c ha n ges i n c o n c o mita nt me ds , a n d c ha n ges i n baseli ne diet.  C ollect all 
c o nc o mita nt me ds pr o vi d e d t o t he s u bject d uri n g t he E G D. 
3) 
C B C wit h differe ntial.  
4) 
Perf or m Es o p ha g o- G astr o- Du o de n osc o p y ( 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 S O Ps . Assess a n d gra d e t he  
 usi n g t he  
.  
1 2. 9  D a y 1 1 3 ( ± 3) 
1) 
Assess t he s u bject f or A Es a n d S A Es . 
2) 
D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns . 
3) 
D oc u me nt a n y c h a n ges t o baseli ne diet . 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 5 9  of 9 8  
C o nfi de nti al  
4) 
. 
5) 
Deter mi ne b o d y w ei g ht . 
6) 
C ollect vital si g ns . 
7) 
Perf or m s y m pt o m -dir ect e d p h ysical e x a m, as nee de d . 
8) 
C B C wit h differe ntial . 
9) 
C he mistr y .  
1 0) Uri nal ysis . 
1 1)  Bl o o d f or P K a n d st or a ge. 
1 2)  S u bjects w h o e nr oll i n t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y will be gi n e xte nsi o n st u d y d osi n g 
i m me diatel y after c o m pl eti n g t he D a y 1 1 3 visit of t he A K 0 0 2- 0 0 3 pr ot oc ol. S u bjects will 
n ot c o m plete t he Da y 1 4 1 pr oce d ures or e xte n de d f oll o w- u p u n der t he A K 0 0 2- 0 0 3 
pr ot oc ol. O pe n-la b el d osi n g a n d f oll o w- u p i ncl u di n g a n y e xte n de d f oll o w- u p re q uire d t o 
m o nit or t he rec o ver y of l y m p h oc ytes a n d e osi n o p hils will occ ur u n der t he A K 0 0 2- 0 0 3 X 
e xte nsi o n pr ot oc ol. 
1 2. 1 0  D a y 1 4 1 ( ± 3 ) P ost -Tre at me nt F oll o w - U p or E arl y Ter mi n ati o n * 
1) 
Assess t he s u bject f or A Es a n d S A Es.   
2) 
D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns . 
3) 
D oc u me nt a n y c h a n ges t o baseli ne diet . 
4) 
. 
5) 
Deter mi ne b o d y w ei g ht . 
6) 
C ollect vital si g ns . 
7) 
Perf or m s y m pt o m -dir ect e d P E, as nee d e d . 
8) 
Uri nal ysis . 
9) 
Uri ne pre g n a nc y test (if s u bject is of c hil d beari n g p ote ntial). 
1 0) C B C wit h differe ntial . 
 
N ote:  T he a bs ol ute l y m p h oc yt e a n d e osi n o p hil c o u nts m ust rec o ver f or t his t o be t he fi nal 
f oll o w- u p visit. S u bjects w h ose e osi n o p hils a n d l y m p h oc ytes d o n ot rec o v er m ust e nter 
E xte n de d F oll o w- U p (see bel o w). 
1 1) C he mistr y . 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 6 0  of 9 8  
C o nfi de nti al  
1 2)  Bl o o d f or A D A . 
1 3)  Bl o o d f or P K a n d st or a ge. 
1 4)  Bl o o d f or E x pl orat or y a n al ysis. 
* Earl y Ter mi nati o n: Perf or m 2 8 ( ± 3) da ys after t he 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 u r e c o m plia nce wit h t he visit. If s u bject disc o nti n ues t he st u d y m ore t ha n 
2 8 da ys after t h e last d ose of st u d y dr u g, t he n perf or m t he E T Visit as s o o n as p ossi ble. 
1 2. 1 1  E xte n de d F oll o w- U p  
S u bjects m ust ret ur n t o t he site e ver y 2 8 ( ± 3) da ys u ntil t he a bs ol ute l y m p h oc yt e a n d e osi n o p hil 
c o u nts rec o v er. D ata c oll ecte d d uri n g E xte n de d F oll o w-U p  will be li mite d t o:  
1) 
C B C wit h differe ntial  
2) 
A d verse E v e nts of S peci al I nt erest  
3)  
Seri o us A d verse E v e nts 
1 3.  A d verse E ve nt R e 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 n ce wit h 2 1 C o de of Fe der al 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 n ce E 2 A, a n a d verse e v e nt ( A E ) is a n y u nt o w ar d 
me dical occ urre n ce i n a cli nical i n vesti gati o n of a s u bject  a d mi nistere d a p h ar mace utic al pr o d uct 
a n d t hat d oes n ot necessaril y ha v e a ca usal relati o ns hi p wit h t he treat me nt. A n A E is t heref ore 
a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y fi n di n g), s y m pt o m, or 
disease te m p orall y ass o ciate d wit h t he a d mi nistrati 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 gati o nal pr o d u ct. 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 v erit y, or fr e q u e nc y i n t he c urre nt I n v esti gat or’s Br oc h ure or of greater se verit y or 
fre q ue n c y t ha n e x pecte d base d o n t he i nf or mati o n i n t he I n v esti gat or’s Br oc h ure.  
E x a m ples of a n A E i ncl u de: 
•  
Si g nifica nt w ors e ni n g or e x acer bati o n of u n d erl 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 x a ms, vital si g ns or la b orat or y tests . 
T he f oll o wi n g e x a m ples are n ot c o nsi dere d A Es: 
•  
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 o ce d ure is us uall y a n 
A E . 
•  
A ntici pate d da y- t o- d a 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 si g nifi ca nt w orse ni n g fr o m bas eli ne d oes n ot occ ur. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 6 1  of 9 8  
C o nfi de nti al  
•  
Si g ns o r s y m pt o ms of t he dis or der bei n g st u die d, u nless t he y b ec o me m ore se vere or occ ur 
wit h a gr eater fr e q ue n c y t ha n occ urri n g at baseli n e . 
All A Es , 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 ot e d o n p h ysi cal 
e x a mi nati o n/la b orat or y t esti 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 b e gi n ni n g after first a d mi nistrati o n of st u d y dr u g a n d e n di n g at Da y 1 1 3 if 
e nr olli n g i n t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y, or Da y 1 4 1 ( ± 3 da ys) or t he E T v isit u nless 
directe d ot her wise b y All a k os. 
1 3. 2  Seri o us A d verse E ve nt s 
A seri o us a d verse e v ent ( S A E ) is defi ne d as a n A E t hat meets t hat o ne of t he f oll o wi n g criteria:  
•  
Deat h  
•  
A life -t hreate ni n g A E t hat places t he s u bject  at ris k of deat h at t he ti me of t he e ve nt. It d oes 
n ot refer t o a n e ve nt t hat h y p ot heticall y mi g ht ca use deat h if it were m ore s e vere.  
•  
I n p atie 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 nca p acit y . 
•  
A c o n ge nital a n o mal y/ birt h defect occ urri n g i n t he offs pri n g of a st u d y s u bj ect.  
•  
Ot her i m p orta nt me dical e ve nts ma y als o be c o nsi dere d a n S A E w he n, bas e d o n a p pr o pri ate 
me dical j u d g m e nt, t he y j e o par dize t he patie nt or re q uire i nter v e nti o n t o pre ve nt o ne of t he 
o utc o mes liste d a b o ve. 
S A Es will be assesse d a n d rec or d e d aft er 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 at 
Da y  1 1 3 if e nr olli n g i n t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y, or D a y 1 4 1 ( ± 3 da ys ) or t he E T v isit 
or t he e n d of t he E xte n de d F oll o w- U p peri o d if a p plica ble, u nless t he S A E is relate d t o a 
scree ni n g pr o ce d ure,  i n w hic h case it will be ca pt ure d fr o m t he d ate of i nf or me d c o nse nt.  
1 3. 3  A d verse E ve nts of S peci al I nterest  
A d verse E v e nts of S peci al I nt erest ( A E SIs) f or t his trial i ncl u de:  
•  
Mali g na n cies c o nfir me d b y hist o pat h ol o gi cal 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, b y d ecreasi n g t heir f u ncti o n, A K 0 0 2 c o ul d t he oreticall y 
i ncreas e 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 ve 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 parasitic a n d o p p ort u nistic i nfecti o ns) 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 6 2  of 9 8  
C o nfi de nti al  
•  
O p p ort u nistic i nfecti o ns (i nfecti o ns k n o w n t o be m ore se vere or o cc 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 ve cli nical la b orat or y test. 
•  
I nf usi o n-relat e d reacti o ns a n d h y p erse nsiti vit y reacti o ns, i ncl u di n g a na p h yl a xis. 
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 at Da y 1 1 3 if e nr olli n g i n t he 
A K 0 0 2 - 0 0 3 X e xte nsi o n st u d y or D a y 1 4 1 ( ± 3 da ys ) or t he E T v isit or t he e n d of t he E xte n de d 
F oll o w- U p peri o d, i f a p plica ble, a n y ne w A E SI ( or ne w i nf or mati o n relate d t o a pre vi o usl y 
re p orte d A E SI) m ust be r ec or de d i n t he A E e C R F a n d desi g nate d as a n “a d verse e v e nt of s pecial 
i nterest.”  
1 3. 4  I nf usi o n-Rel ate d Re acti o ns  
All A d verse E v e nts, c o nsi dere d b y t he I n v esti gat or t o be relat e d t o t he i nf usi o n of t he bi ol o gical 
s u bsta nce, a n d o cc urri n g wit hi n 2 4 h o urs of t he 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 o ne IR R .  
C o m m o n s y m pt o ms of I R Rs i ncl u de ( b ut are n ot e x cl usi ve t o) :  
•  
Fl us hi n g 
•  
C hills  
•  
Bac k or a b d o mi nal p ai n  
•  
C hest disc o mf ort or ti g ht ness 
•  
Dizzi ness  
•  
S h ort ness of breat h 
•  
Hea dac he  
•  
H y p ote nsi o n or h y p erte nsi o n 
•  
Na usea  
•  
V o miti n g  
•  
S weati n g  
•  
Fe ver  
•  
Urticaria  
•  
Pr urit us  
•  
Br o nc h os p as m 


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Date:  0 7 Fe b 2 0 1 9  
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C o nfi de nti al  
All s y m pt o ms e x perie nce d b y a s u bj ect d uri n g a n I R R will be liste d i n t he e C R F u n der o ne 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 hic h case it will be 
rec or d e d se paratel y. T h e 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 tim e 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.   
If t he s u bject e x perie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y dr u g 
i nf usi o n a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of s y m pt o ms, f or 
e x pl orat or y safet y a n al ysis.  
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 care. 
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 dilat ors, will be a vaila ble at all ti mes d uri n g t he c o n d uct of t he st u d y. 
T o defi ne a n a p h ylactic reacti o ns i n a c o nsiste nt a n d o bjecti ve ma n ner, all A Es of s us pecte d 
a na p h yla xis will be e val uate d usi n g Sa m ps o n’s Criteria f or A n a p h yl a xis (A p pe n di x 6 ). 
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 uire m e nt s.  
If a s u bject e x perie nces si g ns or s y m pt o ms of a na p h yla xis, t he s u bject 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 ne, 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 cess ati 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 v e 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 nitrites 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 E e C R F as se p arat e A Es.  
T he I n vest i gat or ( or q ualifie d S u bin vesti gat or) m ust assi g n t he f oll o wi n g A E attri b utes  liste d 
bel o w a n d is res p o nsi ble f or e ns uri n g t heir ca pt ure i n t he s o urce d oc u m e ntati o n. 
1 3. 6. 2  Assess me nt of I nte nsit y 
T he I n vesti gat or will use t heir cli nical j u d g m e nt as well as t he g ui deli nes lai d o ut i n t he Nati o nal 
Ca ncer I nstit ute ( N CI) C o m m o n Ter mi n ol o g y Criteria f or A d v erse E ve nts ( C T C A E) Versi o n 5. 0 
( or m ost c urre nt versi o n) ta bles (Ta ble 2  a n d A p pe n di x 4 ) t o assess t he i nte nsit y of eac h A E  a n d 
S A E.  


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Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
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C o nfi de nti al  
T a ble 2  
A d verse E ve nt  Se verit y per C T C A E  
Gr a de  
C T C A E  Descri pti o n *  
1 
Mil d ; as y m pt o matic or mil d s y m pt o ms; cli nical or dia g n osti c o bser vati o ns o nl y; i nter ve nti o n 
n ot i n dicate d.  
2 
M o derate; mi ni mal, 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 priate 
i nstr u me ntal A D L. 
3 
Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life -t hreate ni n g, h os pitalizati o n  or 
pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g; li miti n g self -care A D L. 
4  
Life -t hreate ni n g c o nse q ue nces, ur ge nt i nter ve nti o n i n dicate d. 
5  
Deat h relate d t o A E . 
* C T C A E v. 5 . 0: Gra de refers t o t he se verit y of t he A E. T he C T C A E dis pla ys Gra des 1– 5 wit h u ni q ue cli nical 
descri pti o ns of se verit y f or eac h A E base d o n t his ge neral g ui deli ne . 
T he ter m “se v er e” is a m eas ure of i nte nsit y, a n d a se vere A d vers e E ve nt ( A E) is n ot necessaril y a 
Seri o us A d verse E v e nt ( S 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 d a y, t he ma xi m u m se verit y f or t he e ve nt 
s h o ul d be e ntere d i nt o t h e A E e C R F . If t he i nte nsit y c h a 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 par atel 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 t heir cli nical j u d g me nt as well as t he g ui deli n es i n  Ta 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 d vers e E ve nt.  
T a ble 3 
A d verse E ve nt R el ati o ns hi p t o St u d y Dr 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 re -c halle n ge test, if p ossi ble). A n ot her eti ol o g y is c o nsi dera 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 s u bj ect’s me 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 pla usi ble te m p oral relati o ns hi p bet wee 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 ote  
A n e ve nt f or w hic h a n alter nati ve e x pl a nati o n is m ore li kel y (e. g., c o nc o mita nt me dicati o ns 
or o n g oi n g me dical c o n diti o ns) or t he te 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 gests 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 ote will be  gr o u pe d t o get her wit h N ot Relate 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 s u bj ect’s u n derl yi n g me 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 heref ore, t he I n vesti gat or belie ves n o relati o ns hi p 
e xists bet wee n t he e ve nt a n d  st u d y dr u g.  


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A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
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C o nfi de nti al  
1 3. 6. 4  Assess me nt of C a us alit y t o St u d y Pr oce d ure 
T he I n vesti gat or s h o ul d use t heir cli nical j u d g me nt as well as t he g ui deli n es i n Ta ble 4  t o assess 
t he relati o ns hi p bet wee n St u d y Pr o ce d ure a n d A d verse E ve nt. As sess 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 u c 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.  
T a ble 4  
A d verse E ve nt R el ati o ns hi p t o St u d y Pr oce d ure  
Rel ati o ns hi p t o  
St u d y Pr 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 relate d t o a st u d y pr oce d ure . 
P ossi ble  
T he e ve nt ca n n ot be e x plai ne d b y t he s u bj ect’s me 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 pla usi ble te m p oral relati o ns hi p bet wee n t he e ve nt a n d a st u d y 
pr oce d ure.  
U nli kel y/ Re m ote  
A n e ve nt f or w hic 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 dicati o ns 
o r o n g oi n g me dical c o n diti o ns) or t he te 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 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 ote 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 s u bj ect’s u n derl yi n g me 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 heref ore, t he I n vesti gat or belie ves n o relati 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 p ect t o st u d y dr u g will be cat e g orize d as n o ne, st u d y dr u g p er ma n e ntl y 
disc o nti n ue d, st u d y dr u g te m p oraril y wit h dra w n, or ot her (s pecif y).  
Acti o n ta ke n wit h res p ect t o st u d y p artici 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 p ati on, or ot her (s pecif y).  
Acti o n ta ke n wit h res p ect t o treat me nt of a n a d v erse e ve nt will be cate g orize d as n o ne, 
c o nc o mita nt me dicati o n, c o nc 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 r es 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, r ec o vere d wit h se q uelae, fatal, or u n k n o w n.  
1 3. 7  A d verse E ve nt R e p orti n g Pr oce d ures  
1 3. 7. 1  All A d verse E ve nts  
A n y cli nicall y si g nifica nt a d verse e ve nt t hat is o n g oi n g at t he ti me of st u d y c o m pleti o n or earl y 
ter mi nati o n will be f oll o we d b y t he I n v esti gat or u ntil e ve nt res ol uti o n, t he a d verse e ve nt is 


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A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
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C o nfi de nti al  
ot her wise e x plai ne d , n ot c o nsi dere d cli nicall y si g nifica nt b y t h e In vesti gat or , or t he s u bject is 
l ost t o f oll o w- u p. 
All A Es i de ntifie d, w het her seri o us or n o n-seri o us, will be rec or d e d i n t he A E e C R F 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 at D a y 1 4 1 ( ± 3 ) or E T . S A Es c o nsi dere d 
relate d t o Scr ee ni n g pr oce d ures will be rec or d e d i n t he A E e C R F starti n g o n t he date of i nf or m e d 
c o nse nt. W he ne ver a p pr o priate, t he C T C A E ( v. 5. 0 or m ost c urre nt versi o n) s h o ul d be utilize d 
f or na mi n g c o m m o n A Es (A p pe n di x 4 ). 
1 3. 7. 2  Seri o us A d verse E ve nt Re p orti n g  
I n t he e ve nt of a n y S A E r e p orte d or o bs er ve d d uri n g t he st u d y, w h et her or n ot attri b uta ble t o t he 
st u d y dr u g, site pers o n nel will re p ort it i m me 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 n e or e m ail t o t he S p o ns or, Alla k os, I n c.  
S A E  re p ort f or ms will be pr o vi de d t o t he i n vesti gati o nal site t o assist i n c ollecti n g, or ga nizi n g, 
a n d re p orti n g S A Es, a n d f or ms s h o ul d be c o m plet e d wit h as m uc h i nf or mati o n as is a vaila ble 
a n d s u b mitte d t o t he S p o ns or wit hi n 2 4 h o urs. S A Es s h o ul d als o be rec or de d o n t he A E e C R F 
a n d desi 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 v esti gat or 
s h o ul d tr y t o ma ke a ca us alit 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 r e p orti n g re q uire me nts. If t he I n v esti gat or or desi g nee is n ot a v aila ble t o si g n t he S A E 
re p ort u p o n i nitial s u b missi o n t he y s h o ul d be c o nt acte d via tele p h o n e a n d t heir assess me nt 
d oc u me nte d o n t he S A E f or m ( wit h a n ote stati n g si g nat ure is f ort hc o mi n g).  T he I n vesti gat or 
m a y c h a n ge  t heir ca us alit y assess me nt b ase d o n f oll o w- u p i nf or mati o n a n d s u b mit a n a me n de d 
S A E re p orti n g f or m.  
All eff orts will be ma de t o o btai n acc ur ate a n d c o m plete me dical rec or ds f or t he S A E. A ll 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 s u bject s o urce. 
T he site will n otif y t he I nstit uti o nal Re vie w B oar d  (I R B) acc or di n g t o its g ui deli nes.  
T he s u bject’s  c o n diti o n will be f oll o we d b y t h e I n vesti gat or or desi g nate d S u bi n vesti gat or u ntil 
res ol uti o n of t he c o n diti o n or a ret ur n t o b aseli ne l e vels. If a d diti o nal visits are re q uire d, t he 
s u bject will be as ke d t o r et ur n t o t he st u d y site f or f urt her f oll o w‐u p. I f t he c o n diti o n is still 
o n g oi n g at t he ti me t he s u bject e xits t he st u d y, e v er 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 he s u bject f or a reas o na ble peri o d of ti me, as deter mi ne d b y t he I n v esti gat or or u ntil t here 
is a ret ur n t o baseli ne or sta bilizati 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 


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a vaila ble, s uc h as h os pital disc har ge n otes a n d p atie nt me dical rec or ds, t he I n vesti gat or will be 
n otifie d a n d pr o vi de d wit h all rele va nt i nf or m ati o n.  
All S A Es t hat ha ve n ot res ol ve d b y t he e n d of t h e st u d y or t hat ha v e n ot res ol ve d o n 
disc o nti n uati o n of t he s u bject’s partici pati o n i n t h e 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 r es ol ves .  
•  
T he e ve nt sta bilizes . 
•  
T he e ve nt r et ur ns t o baseli ne, if a baseli ne v al ue is a vai la ble.  
•  
T he e ve nt ca n be attri b ute d t o a ge nts ot her t ha n t h e 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 u ct.  
•  
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 n e d (s u bject or healt h care 
practiti o ner r ef usal t o pr o vi de a d di ti 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 n ce wit h f oll o w- u p eff orts).  
Seri o us a d verse 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  
  
P h o ne:  + 1 4 4 3- 6 9 9- 5 2 3 0 
 
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  Pre g n a nc y Re p orti n g  
Pre g n a ncies are ca pt ur e d if t he y o cc ur i n fe male s u bjects or i n t he se x ual part ners of m ale 
s u bjects fr o m t he ti me t he s u bject 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 Da y 1 4 1 
( ± 3 da ys ) or E T.  
Fe male s u bjects 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 he I n v esti gat or 
i m me diatel y if t he y b ec o me pre g na nt d uri n g t he st u d y. Mal e s u bjects 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 he I n vesti gat or i m me diat el y if t h eir part ner b ec o mes 
pre g na nt d uri n g t he st u d y. 
T he I n vesti gat or m ust re p ort a n y pre g n a nc y t o Alla k os wit hi n 2 4 h o urs of bec o mi n g a ware of it 
usi n g t he pr o vi de d pre g n a nc y re p orti n g f or ms. T h e s u bject m ust be 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 n c y will n ot be c o nsi dere d a n A E or S A E, b ut all 
pre g na nci es will be f oll o we d t hr o u g h ter m.  
A n y c o n ge nital a b n or m alities n ote d at birt h i n t he offs pri n g of a s u bject w h o recei v e d st u d y dr u g 
will be re p orte d as a n S A E. T he o utc o me of a n y pre g n a nc y a n d t he pres e nce or a bse n ce of a n y 


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c o nge nital a b n or malit y will be rec or d e d i n t he s o urce d oc u m e ntati o n a n d re p orte d t o t he Me dical 
M o nit or a n d S p o ns or.  
1 3. 7. 4  A E SI 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 at Da y 1 4 1 ( ± 3 da ys ) or t he E T 
Visit or t he e n d of t he E xte n de d F oll o w- U p peri o d if a p plica ble, a n y n e w A E SI ( or ne w 
i nf or mati o n relate d t o a pre vi o usl y re p orte d A E SI) m ust be rec or d e d i n t he A E e C R F a n d 
desi g nat e d as a n “a d v ers e e ve nt of s p ecial i nterest.”  
A n A E SI t h at als o q ualifi es as a S A E ( p er Secti o n 1 3. 2 ) m ust als o be re p ort e d as a S A E i n 
acc or d a nce wit h Secti o n 1 3. 7. 2 . A E SIs t hat are als o S A Es m ust be rec or d e d i n t he A E e C R F a n d 
desi g nat e d as b ot h “seri o us” a n d as a n “a d v erse e ve nt of s pecial i nterest.”  T hese will be 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 be re p ort e d t o t he S p o ns or wit hi n 2 4 h o urs of 
site a war e ness. 
1 3. 8  Me dic al M o nit ori n g  
Dr. 
 s h o ul d be c o ntacte d directl y usi n g t he p h o ne n u m bers a n d/ or e mail 
a d dress bel o w t o r e p ort me dical c o ncer ns or f or q uesti o ns re gar di n g safet y. 
  
Alla k os Me dical M o nit or 
 
, M D, P h D  
  
P h o ne: 
 
 
E mail:  
 
1 3. 9  I n de pe n de nt D at a M o nit ori n g C o m mittee 
A n I n de pe n d e nt Data M o nit ori n g C o m mittee (i D M C) has bee n c o n v e ne d f or t his st u d y. T he 
i D M C will meet at esta blis he d i nter vals t hr o u g h o ut t he st u d y a n d will als o c o n ve ne as 
ne cessitate d b y d ata a n d/ or safet y r e vie ws.  
1 3. 1 0  St u d y Wit h dr a w al Criteri a  
Partici pati o n of a s u bject will be disc o nti n ue d i n t he e ve nt t hat: 
•  
Occ urre nce of a n e x cl usi o n criteri o n , w hic h is cli nicall y rele va nt a n d affects t he s u bject’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 v esti gat or a n d/ or S p o ns or. 
•  
Re b o u n di n g of e osi n o p hil c o u nts t o > 1 5 0 0/ µ L i n s u bjects w h o e nter e d t he st u d y wit h 
e osi n o p hil le vels > 1 5 0 0/ µ L, ha d a n i nf usi o n-relat e d reacti o n d uri n g t he first a n d/ or sec o n d 
i nf usi o n, a n d w h ose e osi n o p hil c o u nts were  i nitiall y s u p press e d aft er st u d y dr u g will be 
wit h dra w n fr o m t he st u d y at t he i nstr u cti o n of t he u n bli n de d safet y m o nit or. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 6 9  of 9 8  
C o nfi de nti al  
•  
Ser u m tra nsa mi nases ( A L T a n d/ or A S T) > 3 × 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 bs e 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 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 ors e ni n g 
of s y m pt o ms felt b y t he I n vesti gat or t o b e p ote ntiall y relat e d t o he patic i nfl a m mati o n, s uc h as 
fati g u e, na usea, v o miti n g, ri g ht u p per q ua dra nt pai n or te nder n ess, fe v er, ras h . 
1 3. 1 1  St u d y St o p pi n g R ules  
T he st u d y ma y b e 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 me nt.  
•  
A fatal A E t hat is p ossi bl y or pr o ba bl y relate d t o treat me n t.  
•  
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 hat c o nti n uati o n of t he trial 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.  
Healt h A ut h orities a n d I R B s will be i nf or me d a b o ut t he disc o nti n uati o n of t he trial i n acc or da n ce 
wit h a p plica ble re g ul ati o ns. T he trial ma y be ter mi nate 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 Re pl ace me nt of P atie nts  
1 4. 1  Defi niti o n  of St u d y C o m pleti o n 
A s u bject w h o c o m pletes visits t hr o u g h t he Da y 1 4 1 v isit or t he e n d of t he E xte n de d F oll o w- U p 
peri o d after c o m pleti n g Da y 1 4 1 , if a p plica bl e, will be rec or d e d as ha vi n g c o m plete d t he st u d y. 
A s u bject w h o c o m pletes t he st u d y t hr o u g h t he D a y 1 1 3 Visit a n d e nr olls i n t he A K 0 0 2- 0 0 3 X 
e xte nsi o n pr ot oc ol will be cate g orize d as ha vi n g c o m plete d t he A K 0 0 2- 0 0 3 st u d y. 
1 4. 2  E arl y Disc o nti n u ati o n of St u d y Dr u g  
A s u bject 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 s u bject, t he I n vesti gat or, 
or t he S p o ns or feels t hat it is n ot i n t he s u bject’s best i nterest t o c o nti n ue. 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: 
•  
S u bject wit h dra ws c o nse nt.  
•  
A E t hat, i n t he o pi ni o n of t he I n v esti gat or, res ults i n it bei n g i n t he best i nterest of t he 
s u bject t o disc o nti n ue st u d y treat me nt.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 0  of 9 8  
C o nfi de nti al  
•  
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 trial d uri n g t he d urati o n of t his trial .  
•  
Use of a n o n- per mitte 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 he Me dical 
M o nit or. 
•  
L oss of a bilit y t o fr eel y pr o vi de 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 ncarcerati o n 
f or treat me nt of eit her a ps yc hiatric or p h ysical (e. g., i nfecti o us disease) ill ness.  
If a s u bject is wit h dra w n fr o m treat me nt d ue t o a n A E, t he s u bject will be f oll o we d a n d treat e d 
b y t he I n vesti gat or u ntil t he a b n or mal para meter or s y m pt o m has res ol ve d or sta bilize d .  
All s u bjects 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 ass ess me nts a n d pr oce d ures acc or di n g t o t he 8- wee k f oll o w - u p peri o d i n Ta ble 1 , 
if p ossi ble (i ncl u di n g f oll o w u p E G D).  
Reas o na ble atte m pts will be ma de b y t he I n v esti gat or t o pr o vi de reas o ns f or s u bject wit h dra w als. 
T he reas o n f or t he s u bject’ 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 ur ce d o c 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 t h e 
a nal ysis of t he data fr o m t he st u d y. A se p arate Statistical A nal ysis Pla n ( S A P), w hic h m ust be 
d oc u me nte d as c o m plet e d pri or t o u n bli n di n g t he st u d y, will descri be d ata ha n dli n g a n d 
statistical tec h ni q ues i n f ull detail a n d will s u perse de t he statistical met h o ds detaile d i n t he 
pr ot oc ol. T h e S A P will detail  a n y m o dificati o ns t o t he a nal ysis pla n descri be d bel o w.  
U nless s pecifie d ot her wise, baseli ne will be defi ne d as t he last o bser v ati o n bef ore t h e first I V 
i nf usi o n of t he st u d y dr u g. 
All patie nt data will be liste d. W he n a p pr o priate, s u m ma r y statistics of n u m ber of n o n-missi n g 
val ues, mea n, me dia n, st a n dar d de vi ati 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 pr o p orti o n will be c o m p ute d f or 
cate g orical varia bl es. T w o -si de d 9 5 % c o nfi d e nce i nter vals will be pr o vi de d f or t he mea n a n d 
pr o p orti o n. N o f or mal statistical i nfere nces will be ma de f or safet y para met ers. N o i m p utati o n 
will be use d f or missi n g data.  
U nless s pecifie d ot her wise, safet y dat a will be s u m marize d f or eac h treat me nt gr o u p as well as 
f or t he t w o acti ve d ose gr o u ps c o m bi ne d. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 1  of 9 8  
C o nfi de nti al  
1 5. 1  S a m ple Size  
Ass u mi n g a r e d ucti o n of 3 0 % i n t he n u m ber of e osi n o p hils per H P F  ( pri mar y e n d p oi nt) fr o m 
baseli ne i n t he A K 0 0 2-tr eate d gr o u p v ers us a 1 0 % re d ucti o n per H P F  i n t he place b o gr o u p, a n d 
ass u mi n g a sta n d ar d de vi ati o n of 2 0 %, 2 0 s u bjects per gr o u p w o ul d pr o vi d e 8 7 % p o wer wit h a 
si g nifica n ce le v el of 0. 0 5. He nce, 2 0 s u bj ects per gr o u p w o ul d be m ore t ha n a de q uate fr o m a n 
efficac y pers pecti ve.  
1 5. 2  D at a Sets A n al yze d 
All s u bjects w h o ha ve r ecei ve d  st u d y me dicati o n will be i ncl u de d i n t he Safet y p o p ul ati o n f or 
safet y a n al ysis. S u bjects w h o are ra n d o mize d a n d ha ve recei ve d at least o n e d ose of st u d y 
me dicati o n a n d ha v e a p ost - baseli ne efficac y assess me nt will be i ncl u de d i n t he M o difie d I nte nt-
t o-Tre at ( MI T T) p o p ulati o n f or efficac y a nal ys is. T he st u d y statisticia n al o n g wit h t he st u d y 
tea m will re vie w pr ot o c ol de viati o ns t o i de ntif y s u bjects t o be e x cl u de d fr o m t he per Pr ot oc ol 
A nal ys is p o p ulati o n.  
1 5. 3  De m o gr a p hic a n d B aseli ne C h ar acteristics  
T he f oll o wi n g d e m o gra p hic a n d baseli ne v aria bles will be s u m marize d:  
•  
De m o gra p hics 
•  
Me dical hist or y  
•  
C o m plete p h ysical e x a m  
•  
E C G at scree ni n g  
•  
Scree ni n g vital si g ns a n d la b orat or y tests  
1 5. 4  S u bject Dis p ositi o n  
T he n u m ber a n d p erce 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 he 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 af et y E n d p oi nts  
A d verse E ve nts : All A Es will be c o de d usi n g t h e Me dical Dicti o nar y f or R e g ul at or y Acti vities 
( Me d D R A) a n d will be classifie d b y M e d D R A s yste m or ga n class ( S O C) a n d preferre d t er m. 
Listi n gs will i ncl u de all A Es c ollecte d o n st u d y. T he s u m maries of A Es will be base d o n T E A Es, 
defi ne d as a n A E r e p orte d i n t he cli nical data bas e 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 V i nf usi o n of t he st u d y me dicati o n.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 2  of 9 8  
C o nfi de nti al  
S u bject i nci de nce ( N a n d %) of T E A Es will be s u m marize d as f oll o ws :  
•  
O ver vie w of T E A Es t o i ncl u de 
–  N u m ber ( %) of patie nts w h o re p orte d at least o ne T E A E o verall, b y se v erit y, a n d b y 
relati o ns hi p 
–  N u m ber ( %) of patie nts w h o re p orte d at least o ne seri o us T E A E  
–  N u m ber ( %) of patie nts w h o re p orte d 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 orte d at least o ne T E A E SI 
•  
T E A Es b y pref err e d ter m  
•  
T E A Es b y S O C a n d pref erre d t er m  
•  
T E A Es b y m a xi m u m se verit y, S O C, a n d preferre d ter m  
•  
Dr u g -r elate d T E A Es b y S O C a n d preferre d t er m  
•  
T E A Es lea di n g t o wit h dr a wal b y S O C a n d pr eferre d ter m  
•  
Seri o us T E A Es b y S O C a n d pref erre d ter m  
•  
T E A E s of s peci al i nterest ( T E A ESI ) b y S O C a n d preferre d t er m  
Cli nic al L a b or at or y Assess me nts:  Sa m ples will be o btai ne d f or t h e cli nical la b orat or y tests 
i de ntifie d i n Secti o n 1 1. 4 , a n d la b orat or y t ests t o be s u m marize d i ncl u de c h e mistr y, he m at ol o g y, 
uri nal ysis, a n d A K 0 0 2 A D A.  
Descri pti ve statistics will be use d t o s u m marize la b orat or y res ults at bas eli ne, 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 marize t he la b orat or y res ults 
relati ve t o n or mal r efere n ce ra n ges at bas eli ne a n d eac h p ost-b aseli ne ti me p oi nt.  
Vit al Si g ns:  Vital si g ns will be s u m marize d at baseli ne, eac h visit, a n d c ha n ge fr o m baseli ne at 
eac h visit.  
E C G:  S u bject i nci de n ce of t he I n vesti gat or’s o v erall assess me nt ( n or mal, a b n or mal – n ot 
cli nicall y si g nifica nt, a n d a b n or mal – cli nicall y si g nifica nt) will be s u m mari ze d.  
P h ysic al E x a m:  N e w or w orse ni n g s y m pt o ms i n t he s y m pt o m-directe d p h ysical e x a m s will be 
i ncl u de d i n t he b y-s u bject data listi n g.  
C o nc o mit a nt Me dic ati o ns:  All me dicati o ns ( pri or a n d c o nc o mita nt) will be c o de 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 ( W H O D D). 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 p e utic C he mical ( A T C ) Class a n d preferre d t er m.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 3  of 9 8  
C o nfi de nti al  
1 5. 6  Effic ac y A n al ysis 
Pri m ar y Effic ac y E n d p oi nt A n al ysis:  T he pri mar y efficac y a nal ysis  is t he perce nt c ha n ge fr o m 
baseli ne  i n t he n u m ber of e osi n o p hils per H P F  i n gastric or d u o de n al m uc os a. F or s u bjects w h o 
pr o vi de gastric or d u o d e nal o nl y bi o ps y, t he calc ulati o n will be base d o n t he a vera ge c o u nt of t he 
hi g hest r ea di n gs fr o m t he res pecti ve m u c osa at bas eli ne a n d Da y 9 9. F or s u bjects w h o pr o vi de 
b ot h gastric a n d d u o de n al bi o psies, t he calc ulati o n will be base d o n t he a v era ge c o u nt of t he 
hi g hest r ea di n gs fr o m t he c o m bi ne d p o ol of gastric a n d d u o de nal m uc osa. T his e n d p oi nt will be 
s u m marize d b y treat me nt gr o u p. Bet w ee n d os e a n d place b o gr o u p c o m paris o ns i n t he perce nt 
c ha n ge will be carrie d o ut b y a n al ysis of c o vari a nce ( A N C O V A) wit h baseli ne val ue a n d  
ra n d o mizati o n strat u m as c o variates.  Missi n g e osi n o p hil c o u nts at Da y 9 9 will be m ulti pl y 
i m p ute d usi n g baseli ne, r a n d o mizati o n stratificati o n, a n d ot her rele va nt varia bles as c o v ariates. 
Se nsiti vit y a n al ys es will be carrie d o ut t o de m o nstrate t he r o b ust ness of t he treat me nt effe ct:  
•  
T he C oc hra n -Ma ntel -H ae nszel ( C M H) test stratifie d b y t h e ra n d o mizati o n stratificati o n 
varia ble.  
•  
A res p o n der a nal ysis b y t he C M H test, w here t h e res p o n der is defi n e d as t h e e osi n o p hil 
c o u nt ≤3 0 cells/ H P F. 
•  
T he A N C O V A of t he l o g -tra nsf or me d n u m ber of e osin o p hils as t he res p o nse varia ble a n d 
l o g-tr a nsf or me d b aseli ne a n d pri mar y dia g n osis as c o variates. 
•  
A se nsiti vit y a nal ysis t hat is si milar t o t he pri mar y a nal ysis. I nstea d of ass u mi n g missi n g at 
ra n d o m, t his a nal ysis ass u mes missi n g n ot at ra n d o m i n t he m ulti ple i m p utati o ns. 
T o c o ntr ol f or t he t y pe- 1 err or, t he Gate k ee pi n g pr oce d ure  will be f oll o we d. S pecificall y, t he 
hi g h - d ose gr o u p ( Tr eat m e nt Gr o u p 1, Secti o n 3. 2. 1) will be c o m pare d t o t he place b o gr o u p at t he 
2- si de d α = 0. 0 5 le v el first. If t his c o m paris o n is statisticall y si g nifica nt, t he l o w-d ose gr o u p 
( Treat me nt Gr o u p 2) will be c o m par e d t o t he place b o gr o u p als o at t he 2-si de d α = 0. 0 5 le v el. If 
t he first c o m paris o n d oes n ot de m o nstrate statistical si g nifica nce, t h e sec o n d c o m paris o n will 
a ut o maticall y b e c o nsi dere d n ot si g nifica nt.  
T he Gate k ee pi n g pr o ce d ure is a d de d f or m ulti plicit y a dj ust me nt d ue t o t he c o m paris o n of 2 d ose 
gr o u ps t o t he place b o gr o u p. 
T he m et h o d of m ulti ple i m p utati o ns f or missi n g data is a d de d t o t he pri mar y e n d p oi nt a n d t h e 
first seco n dar y e n d p oi nt a nal ys es.  
Sec o n d ar y Effic ac y E n d p oi nt A n al yses:  T he t otal s y m pt o m sc ore ( T S S), t he c o m p osite sc ore 
of i nterest ( C SI), a n d t he d o mai n sc ores of t he P R O s y m pt o m i nte nsities will be s u m marize d 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 4  of 9 8  
C o nfi de nti al  
wee kl y f or eac h patie nt . T he wee kl y c ha n ge s c ores  will be a nal yze d usi n g t he M M R M m o del 
wit h treat me nt, visit, a n d treat me nt -b y -visit i nteracti o n as fi x e d fact ors, baseli ne as c o vari ates, 
a n d s u bject as r e peat e d meas ure u nit.  
T he c o m paris o n bet w ee n t he acti ve d ose gr o u ps a n d t he place b o gr o u p will be base d o n t he 
a vera ges of t he last 6 w ee ks ( Wee ks 9 t hr o u g h 1 4), a n d t he last 2 wee ks ( Wee ks 1 3 a n d 1 4) pri or 
t o bi o ps y, f or w ee kl y T S S, C SI, a n d s y m pt o m sc ores usi n g si m ple c o ntrasts. P- val ues a n d 
c o nfi de nce i nter vals will be prese nt e d wit h o ut m ulti plicit y a dj ust me nt. Details of t he a nal yti cal 
met h o ds will be i ncl u de d i n t he S A P. 
A res p o n der a nal ysis c o m pari n g A K 0 0 2 a n d place b o will be perf or me d. A res p o n der is a p atie nt 
w h o e x hi bits a > 3 0 % re d ucti o n i n C SI (a b d o mi nal pai n, na usea, a n d diarr h ea) a n d a > 7 5 % 
red ucti o n i n m uc osal e osi n o p hils.  
Baseli ne  f or P R O will be calc ulate d usi n g all P R O assess me nts c ollecte d pri or t o ra n d o mizati o n.  
C ha n ge i n t he n u m b er of 
 fr o m baseli ne will be a nal yze d usi n g t he 
sa me M M R M met h o d. 
C ha n ge i n t he n u m b er of e osi n o p hils i n gastric m u c osa i n patie nts wit h E G a n d i n d u o de nal 
m uc osa i n patie nts wit h E G E will be a nal yz e d usi n g t he sa m e met h o d as f or t he pri mar y efficac y 
e n d p oi nt.  
1 5. 7  S u bject  C o nfi de nti alit y  
S u bject  i de ntit y s h o ul d be c o nfir me d  b y t h e pres e ntati o n of a p h ot o i de ntificati o n t o e ns ure t he 
c orrect i n di vi d ual is c o nse nte d, scr ee ne d, a n d e nr olle d (if eli gi ble).  
O nl y t he PI D , s u bject i nitials, a n d de m o gra p hics will be rec or d e d i n t he e C R F. If t he s u bject 
na me a p pears o n a n y s o urce d oc u m e nt c ollecte d (e. g., h os pital disc h ar ge s u m mar y), it m ust be 
re m o ve d fr o m t he d o c u m e nt if t he 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 v e n d or n ot per mitte d access t o s u bject 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 d ata bases. T h e s u bjects 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 RB 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 ollecte d. S u bjects will be i nf or me d t hat all pers o nal 
i nf or mati o n ma de a v aila ble f or i ns pecti o n will be ke pt c o nfi de ntial t o t he e xte nt per mitte d b y all 
a p plica ble state, l ocal, a n d fe der al data  pr ot ecti o n/ pri vac y la ws a n d/ or re g ul ati 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 he tri al are p u blis he d, t he s u bject’s i de ntit y will re mai n 
c o nfi de ntial.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 5  of 9 8  
C o nfi de nti al  
At st u d y c h ec k -i n t o t he st u d y site, s u bjects will be a d vise d n ot t o s hare t h eir st u d y i nf or mati o n 
wit h ot her s u bjects.  
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 me nts  
All staff at partici p ati n g cli nical sites will a d here t o g o o d d oc u m e ntati o n p ractices. D ata will be 
e ntere d i nt o e C R Fs usi n g s o urce d oc u m e nt data. S o urce d oc u m e nts ma y i ncl u de b ut are n ot 
li mite d t o la b orat or y dat a, rec or d e 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 n ce.  
1 6. 2  D at a M a n a ge me nt Pr oce d ures  
T he data will be e nt ere d i nt o a vali date d data b ase.  T he Data M a na ge m e nt gr o u p will be 
res p o nsi ble f or d ata pr ocessi n g, i n acc or d a nce wit h pr oce d ural d oc u me ntati o n. Data base l o c k 
will occ ur o nce q u alit y ass ura nce pr oce d ures ha v e bee n c o m plete d.  
All pr oce d ures f or t he h a n dli n g a n d a n al ysis of d ata 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 o o d a n d Dr u g A d mi nistrati o n ( F D A) g ui d eli 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 dat a ha ve b ee n e ntere d i nt o t he st u d y d ata bas e, 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 plie d t o t he dat a base o n a re g ular basis. Q ueries are e nt ere d, 
trac ke d, a n d res ol ve d t hr o u g h t he electr o nic d ata ca pt ure s yste m directl y. T he st u d y d ata base will 
be u p date d i n acc or d a nce wit h t he res ol ve d q ueri es. All c ha n ges t o t he st u d y dat a base will be 
d oc u me nte d.  
1 6. 4  D at a b ase L oc k/ Discl os ure of R a n d o miz ati o n C o de 
T he data bas e will be l oc k e 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 . 
•  
All a d verse e ve nts ar e c o de d t o t he satisfacti o n of t he C hief Me dical Officer . 
•  
All me dicati o ns are c o de d t o t he satisfacti o n of t h e C hief Me dical Officer . 
•  
All data q ueries h a ve bee n res ol ve d .  
•  
All decisi o ns ha ve bee n ma de re gar di n g all pr ot o c ol vi olati o ns a n d I T T p o p ulati o n 
e x cl usi o ns. 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 6  of 9 8  
C o nfi de nti al  
•  
Writte n a ut h orizati o ns t o l oc k t he data bas e are o bt ai 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. T h e ra n d o mizati o n c o de f or t his st u d y will n ot 
be re veale d u ntil t he pre vi o us prec o n diti o ns are f ulfille d a n d d oc u me ntati o n of t he data bas e 
l oc k is c o m plete. 
1 6. 5  Arc hi vi n g  of D at a 
T he data bas e is safe g u ar de d a gai nst u na ut h orize d access b y esta blis he 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 bas e a n d relate d s oft ware files w ill be mai ntai ne d. 
Data bases  are b ac k e d u p b y t he d ata base a d mi nistrat or i n c o nj u ncti o n wit h a n y u p d ates or 
c ha n ges t o t he dat a base.   
At critical j u nct ures of t he pr ot oc ol (e. g., pr o d ucti o n of i nteri m re p orts a n d fi nal re p orts), d ata f or 
a nal ysis is l oc ke d a n d clea ne d per esta blis he d pr o ce d ures.  
1 6. 6  A v ail a bilit y a n d Rete nti o n of I n vesti g ati o n al Rec or ds 
I n acc or da n ce 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 ul at 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 he st u d y, t he S po ns or or its desi g n ee will retai n a c o p y 
of all st u d y r ec 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 years after n otificati o n 
t hat t he in vesti gati o ns ha ve bee n disc o nti n ue d a n d t he F D A h as bee n n otifi e 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 v e d. T he trial master file will be create d d uri n g t he 
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 he d urati o n of t he 
pr oject , a n d c ollat e d at t h e e n d of t he st u d y. T he files will c o ntai n f ol ders t h at ma y i n cl 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 na ncial a gree me nts  
•  
Re g ulat or y d o c u me nts 
•  
I E C D o c u me nts  
•  
Dr u g Acc o u nta bilit y 
•  
C orres p o n de nce 
•  
Me dical Re p orts  
•  
Patie nt  Data  
•  
M o nit ori n g Visit Re p orts  
•  
Sa m ple C R Fs a n d C R F G ui deli nes 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 7  of 9 8  
C o nfi de nti al  
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 pres e 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 gat 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 ul at or y a ut h orities t o c o n d uct o n- site 
m o nit ori n g a n d/ or a u diti n g of all a p pr o priat e st u d y d oc u m e ntati o n. 
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 be c o n d ucte d i n a ma n ner c o nsiste nt wit h t he Declarati 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 v esti gat ors ( 2 1 C F R 3 1 2 a n d I C H E 6). T h e I n vesti gat or m ust als o c o m pl y wit h all a p plica ble 
pri vac y r e g ulati o ns (e. g., t he HI P A A, E ur o p ea n U ni o n Data Pr otecti o n Directi ve 9 5/ 4 6/ E C).  
1 7. 1  Pr ot oc ol A me n d me nts  
A n a me n d me nt m ust be a gr ee d t o i n writi n g b y Alla k os, I nc. a n d s u b mitte d t o t he healt h 
a ut h orit y as a Cli nical Trial A p plicati o n/ I n v esti gati o nal Ne w Dr u g (I N D) 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 x ce pt as necessar y t o 
eli mi nate i m me diate safet y hazar ds t o patie nts. Writte 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 nate i m me diate hazar d t o 
t he 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. A n y Pr ot oc ol 
A me n d me nts m ust als o be si g ne d b y t he I n vesti gat or.  
1 7. 2  I n de pe n de nt Et hics C o m mittees  
T he pr ot oc ol a n d I C F will be re vie w e d a n d a p pr o v e d b y t h e I nstit uti o nal Re vie w B oar d ( I R B) of 
eac h p artici pati n g st u d y site pri or t o st u d y i nitiati o n. A Ce ntral I R B ma y b e use d if per mitte d b y 
t he partici pati n g st u d y sit e. All S A Es, re gar dl ess of ca usalit y, will be re p ort e d t o t he I R B i n 
acc or d a nce wit h t he sta n dar d o per ati 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 kee p t he I R B i nf or me d as t o t he pr o gress of t he st u d y. T h e I n vesti gat or will o btai n ass ura nce 
of I R B c o m plia n ce wit h r e g ul ati o ns.  
A n y d o c 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 oc ol, pr ot oc ol 
a me n d me nts, I n vesti gat or’s Br oc h ur e, I C Fs, 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 ns ati o n pr oce d ur es, 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 Bs 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 b ef or e 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 v esti gati o nal site m ust be a vaila ble t o Alla k os pri or t o t he 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 x act pr ot oc ol title a n d n u m ber a n d s h o ul d i de ntif y 
t he d oc u me nts re vie we d a n d t he date of re vie w.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 8  of 9 8  
C o nfi de nti al  
T he I R B m ust be i nf or m e d of re visi o ns t o ot he r d oc u me nts ori gi n all y s u b mitte d f or re vie w; 
seri o us a n d/ or u ne x pecte d a d verse e x perie nces o cc urri n g d uri n g t he st u d y i n acc or d a nce wit h t he 
sta n dar d o per ati n g pr oce d ures a n d p olicies of t h e I R B; ne w i nf or mati o n t hat ma y affect 
a d versel y t he s afet y of t h e s u bjects of t he c o n d u ct 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 re-a p pr o v al; a n d w he n t he st u d y has b ee 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 me nt, all s u bjects m ust c o nse nt t o partici pate.  
I n acc or da n ce wit h I C H G C P G ui deli ne E 6 Secti o n 4. 3. 3, s u bjects s h o ul d be as ke d w h et her t he y 
w o ul d li ke t heir P C P n otifie d of t heir st u d y partici pati o n. If yes, t he P C P will be n otifie d i n 
writi n g . Ot her wise, t he s u bject s h o ul d si g n a f or m stati n g t hat he/s he d o es n ot wis h t o discl ose 
s uc h i nf or mati o n.  
T he pr ocess of o btai ni n g t he i nf or me d c o nse nt will be c o m pl y wit h all fe deral re g ulati o ns, I C H 
re q uire me nts, a n d l o cal l a ws.  
T he I n vesti gat or or a desi g nee will re vie w t h e st u d y a n d t h e I C F wit h eac h p ote nt ial s u bject. T he 
re vie w will i ncl u de t he n at ure, sc o p e, pr oce d ures, a n d p ossi ble c o nse q ue n ces 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 s u bject. T he 
I n v esti gat or or desi g nee a n d t he s u bject m ust b ot h si g n a n d d ate t he I C F aft er re vi e w a n d b ef ore 
t he s u bject ca n p artici pat e i n t he st u d y. T h e s u bject will recei ve a c o p y of t h e si g ne d a n d date d 
f or m, a n d t he ori gi nal will be retai ne d i n t he site’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 s u bject t hat st u d y partici p ati o n is e ntirel y v ol u ntar y a n d t h at c o nse nt re gar di n g 
st u d y partici p ati o n ma y b e 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 
s u bject is ot her wise e ntitle d.  
I n a d diti o n, pri or t o u n der g oi n g bi o psies, s u bjects will pr o vi de i nf or me d c o nse nt i n acc or d a nce 
wit h t he sta n dar d o per ati n g pr o ce d ur es a n d p olici es of t he E G D facilit y/ i n vesti gati o nal sites.  
1 7. 4  P u blic ati o ns  
T he pre p arati 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 r es ults s hall be 
i n acc or d a nce wit h a pr o cess 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 pecti ve site. T he 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 Healt h I ns ura nce P orta bilit y a n d 
Acc o u nta bilit y Act ( HI P A A) of 1 9 9 6.  
1 7. 5  Cli nic al Tri al Re gistr ati o n  
T his cli nical trial is  re gistere d o n t he Cli nical T rial Re gistr y W e bsite, w w w. Cli nical Trials. g o v , 
N C T # 0 3 4 9 6 5 7 1.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 7 9  of 9 8  
C o nfi de nti al  
1 7. 6  P a y me nt t o S u bjects  
All s u bjects ma y b e c o m pe nsate d f or p artici pati n g i n t his st u d y, i n acc or d a nce wit h t he pa y me nt 
a m o u nts per st u d y d a y state d i n t he s u bject’s si g n e d I C F a p pr o ve d b y t he IR B . If t he s u bject is 
disc o nti n ue d fr o m t he st u d y pri or t o t he l ast st u d y visit, t he s u bject 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 rat a basis, as state d i n t he s u bject’s I C F. S u bj ects ma y be 
rei m b urse d f or e x pe nses ass ociate d wit h atte n di n g st u d y visits. N o a d diti o nal 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 vesti g at or Res p o nsi bilities  
B y si g ni n g t he A gree me nt of I n v esti gat or f or m, t he I n vesti gat or a grees t o:  
1)  
C o n d uct t he st u d y i n acc or da nce wit h t he pr ot oc ol a n d o nl y ma k e c ha n ges after n otif yi n g 
t he S p o ns or ( or desi g nee), e x ce pt w he n t o pr otect t he safet y, ri g hts, or w elfare of s u bjects.  
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 hat t he r e q uire m e 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 vi e w a n d 
a p pr o val meet 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 Es t hat occ ur i n t he c o urs e of t he st u d y, i n 
acc or d a nce wit h 2 1 C F R Part 3 1 2. 6 4 a n d I C H G ui deli ne E 2 A.  
5)  
E ns ure t hat all ass ociat es, c ollea g ues a n d e m pl o ye es assisti n g i n t he c o n d u ct of t he st u d y 
are i nf or m e d a b o ut t heir o bli gati o ns i n meeti n g t h e a b o ve c o m mit me nts.  
6) 
Mai ntai n a de q uate a n d acc urat e rec or ds i n acc or d a 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 k e t h ose rec or ds a v aila 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 hat a n I R B t hat c o m plies wit h t he 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 nitial a n d c o nti n ui n g re vie w a n d a p pr o val of t he 
cli nical st u d y.  
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 h a n ges i n t he researc h 
acti vit y a n d all u na ntici pate d pr o ble ms i n v ol vi n g ris ks t o patie nts or ot hers (t o i ncl u de 
a me n d me nts a n d I N D saf et y r e p orts).  
9) 
See k I R B a p pr o val bef or e a n y c h a n ges are ma d e i n t he researc h st u d y, e x ce pt w he n 
ne cessar y t o eli mi nate 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 gati o ns of cli nical I n vesti gat ors a n d 
all ot her perti ne nt r e 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 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 8 0  of 9 8  
C o nfi de nti al  
1 8.  Ref ere nces  
Al h m o u d T, Ha ns o n J, Paras her G. E osi n o p hilic gastr oe nteritis: a n u n der di a g n os e d c o n diti o n. 
Di g Dis Sci, 2 0 1 6; 6 1: 2 5 8 5 – 9 2. 
B oc h ner B. Si glec- 8 o n h u ma 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 n cti 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, P ut na m P, Fra n ci osi J, K us h ner J, et al. Hist ol o gic e osi n o p hilic 
gastritis is a s yste mic dis or der ass o ciate 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 gastri c tra nscri pt o me. J Aller g y Cli n I m m u n ol 2 0 1 4; 
1 3 4: 1 1 1 4- 2 4 
H u ds o n S, Herr ma n n H, D u J, C o x P, Ha d da d el B, B utler B, et al. De v el o p me ntal, mali g na n c y-
relate d, a n d cr oss-s p ecies a nal ysis of e osi n o p hil, mast cell, a n d bas o p hil si glec- 8 
e x pressi o n. J Cli n I m m u n ol 2 0 1 1; 3 1( 6): 1 0 4 5- 5 3. 
J e nse n E T, Marti n C F, K a p pel ma n M D, D ell o n E S. Pre 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 nistrati ve Data bas e. J 
Pe diatr Gastr oe nter ol N utr  2 0 1 6; 6 2: 3 6- 4 2. 
Katz P, Gers o n L, Vela M.  G ui deli nes f or t he Di a g n osis a n d M a na ge me nt of Gastr oes o p h a geal 
Refl u x Disease. T he A m erica n J o ur nal of G astr oe nter ol o g y, 2 0 1 3; 1 0 8: 3 0 8 – 3 2 8. 
L ó pez- Me di n a G, G all o M, Pra d o A, Vic u na- H o n orat o I, Díaz de Le ó n R. E osi n o p hilic 
gastr o e nteritis: case re p ort a n d re vie w i n searc h f or dia g n ostic k e y p oi nts. Case Re p 
Gastr oi ntest Me dic i ne, 2 0 1 5; 2 3 9 5 0 6: 1 – 5. 
Ma ns o or E, Sale h M, C o o per G. Pre v ale nce of e osi n o p hilic 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 p at ol, 2 0 1 7; 1 5: 1 7 3 3- 4 1. 
Pr ussi n C. E osi n o p hilic gastr oe nteritis a n d relate d e osi n o p hilic dis or ders. G astr oe nter ol Cli n 
N ort h A m 2 0 1 4; 4 3: 3 1 7- 2 7. 
Ree d C, W o osle y J, Dell o n E. Cli nical c haracteristics, treat me nt o utc o mes a n d res o urce 
utilizati 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 v er Dis 2 0 1 5; 
4 7: 1 9 7- 2 0 1. 
Sa m ps o n H, M u n oz- F url o n g A, Ca m p b ell R, A d ki ns o n Jr. N, B oc k S, Bra n u m A, et al. Sec o n d 
s y m p osi u m o n t he defi niti o n a n d ma na ge me nt of a na p h yl a xis: s u m mar y re p ort--Sec o n d 
Nati o nal I nstit u te of Aller g y a n d I nfecti o us Diseas e/ 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 Aller g y Cli n I m m u n ol 2 0 0 6; 1 1 7( 2): 3 9 1 – 7. 
Z ha n g M, Li Y. E osi n o p hilic gastr o e nteritis: A state - of-t h e-art re vie w. J Gastr oe nter ol H e pat ol 
2 0 1 7; 3 2: 6 4- 7 2.  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 8 1  of 9 8  
C o nfi de nti al  
1 9.  A p pe n dices  
1 9. 1  A p pe n di x 1: P R O Q uesti o n naire  
1 9. 2  A p pe n di x 2: 
 
1 9. 3  A p pe n di x 3: Baseli ne Di et Assess me nt  
1 9. 4  A p pe n di x 4: C o m m o n Ter mi n ol o g y Criteri a f or A d verse E v e nts v. 5. 0  
1 9. 5  A p pe n di x 5: E G D Hist ol o g y  
1 9. 6  A p pe n di x 6: Sa m ps o n’s Criteria of A na p h yl a xis  
1 9. 7  A p pe n di x 7: 
 
1 9. 8  A p pe n di x 8: Bi o mar ker S u b- St u d y f or Selecte d Sites  
1 9. 9  A p pe n di x 9: A d diti o nal Q uesti o ns f or At o pic C o n diti o ns   
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 8 2  of 9 8  
C o nfi de nti al  
1 9. 1  A p pe n di x 1 : P R O Q uesti o n n aire  
 
 
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 8 3  of 9 8  
C o nfi de nti al  
A p pe n di x 1: P R O Q uesti o n n aire c o nt.  
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 8 4  of 9 8  
C o nfi de nti al  
A p pe n di x 1: P R O Q uesti o n n aire c o nt.  
 














Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 9 1  of 9 8  
C o nfi de nti al  
1 9. 3  A p pe n di x 3: B aseli ne Diet Assess me nt   
I nstr ucti o ns: T o be c o m plete d b y St u d y P ers o n nel, t hr o u g h direct i nter vie w wit h St u d y P artici pa nt. Please as k 
q uesti o ns t o St u d y P artici pa nts, m uc h as t he y a p pear bel o w. T his Assess me nt s h o ul d be c o n d ucte d o n Da y 1 of t he 
Scree ni n g P eri o d.  
1.  
Are y o u o n S pecific, D oct or - Prescri be d Diet ?  
Yes ☐ 
N o ☐ 
 
If Yes, what is t he d iet? 
 
☐ Ele me ntal  
[If tic ke d-e nteral/t u be fee di n g? ]  
Yes ☐  
N o ☐ 
 
☐ 6- f o o d or 3 F o o d Eli mi nati o n Diet  
 
☐ S u p ple me ntal Pr otei n S ha ke/ dri n k  s pecif y:  
 
 
☐ Ot her; descri be:  
 
2.  
D o y o u h a ve a n y c o nfir me d f o o d aller gies  
Yes ☐ 
N o ☐ 
(i.e., c o nfir me d b y s ki n -pric k testi n g  or bl o o d tests ) ? 
 
If Yes, what are t he y?   
 
  
 
 
3.  
D oes e ati n g cert ai n f o o ds see m t o m a ke y o ur E G/ E G E w orse ?  
Yes ☐ 
N o ☐ 
 
If Yes, what are t he 3 s pecific f o o ds/t y pes of f o o ds t hat ma ke t he effects w orse?  
F o o d or T y pe of F o o d  
Effect  
 
 
 
 
 
 
4.  
D o y o u a v oi d e ati n g a n y s pecific f o o ds or t y pes of f o o ds  
Yes ☐ 
N o ☐ 
d ue t o y o ur E G/ E G E ?  
 
If Yes, whic h f o o ds are al w a ys  a v oi de d?   
 
  
 
 
5.  
D o y o u a v oi d ? ( tic k all t h at are a p pr o pri ate) 
 
☐ Mil k  
☐ E g g  
☐ W heat  
☐ S o y  
 
W h at are t he m ai n f o o ds t h at Y O U D O e at ?  
 
If a f ull diet is eate n d o n ot list all t y pes of f o o ds, j ust write “ All f o o ds. ” 
  
 
 
6.  
D o y o u a v oi d e ati n g at cert ai n ti mes of t he d a y t o a v oi d s y m pt o ms of E G/ E G E ? 
Yes ☐ 
N o ☐ 
  
If Yes, please descri be:  
 
  
 
 




Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 9 3  of 9 8  
C o nfi de nti al  
1 9. 5  A p pe n di x 5: E G D Hist ol o g y 
Details f or c ollecti n g, la b eli n g, a n d s hi p pi n g s peci me ns will be pr o vi de d se paratel y. 
St ai ni n g  
T he perf or ma nce of t he e val uati o ns liste d bel o w will re q uire 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 ptas e; 3) tric hr o m e 
•  
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 ptas e; 3) tric hr o m e  
Bi o psies will be o bt ai ne d f r o m t he f oll o wi n g:  
•  
Es o p h a g us  (O N L Y if s u bject has c o nc o mita nt E o E)  
–  A set of 2 fr a g me nts fr o m t he distal es o p ha g us 
–  A set of 2 fr a g me nts fr o m t he 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 b e c ollecte d if t here are a n y a d diti o nal areas of i nterest  
  
A c o u nt of ≥1 5 e osi n o p hils per H P F  i n at least o ne es o p ha geal site will be c o nsi dere d 
dia g n ostic of e osi n o p hilic es o p ha gitis.  
•  
St o m a c h  
–  A set of 4 s peci me ns fr o m se parate areas of t he 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 me ns fr o m se parate areas of t he gastric c or p us (t w o fr o m t he pr o xi mal 
lesser c ur v at ure a n d t w o fr o m t he greater c ur vat ure) 
–  U p t o 2 e xtra s peci me ns ma y b e c ollecte d if t here are a n y a d diti o nal areas of i nterest  
 
A c o u nt of ≥3 0 e osi n o p hils per H P F  i n at least 5 H P F s will be c o nsi dere d di a g n o stic of 
e osi n o p hilic gastritis . 
•  
D u o de n u m  
–  4 fra g me nts of d u o d e nal m uc osa fr o m t he sec o n d a n d t hir d part of t he d u o d e n u m.  
–  U p t o 2 e xtra s peci me ns ma y b e c ollecte d if t here are a n y a d diti o nal areas of i nterest  
 
A c o u nt of ≥3 0 e osi n o p hils per H P F  i n at least 3 H P Fs  will be c o nsi dere d di a g n ostic of 
e osi n o p hilic gastr o e nteritis . 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 9 4  of 9 8  
C o nfi de nti al  
T he f oll o wi n g will be re p orte 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 P F   
•  
Ma xi m u m n u m ber of tr y ptase -p ositi ve mast cells per H P F  
I n a d diti o n, t he f oll o wi n g hist o pat h ol o gic para met ers will be gra d e d fr o m 0 (a bse nt) t o 3 
( mar ke d or s e ver e): 
•  
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 p er plasia  
•  
s p o n gi osis 
•  
s u be pit helial tiss ue prese nt ( Y/ N) 
•  
l a mi n a pr o pri a fi br osis: ( gr a 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 orte d f or g astric bi o psies:  
•  
C o nfir mati o n of a bse nce of H. pyl ori . A hi g hl y s e 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 patie nt ca n be i ncl u de d i n t he st u d y a n d t h e 
f oll o wi n g hist o pat h ol o gi c para m eters will be gra d e d usi n g t he S y d ne y S yst e m fr o m 0 
(a bse nt) t o 3 ( mar ke d or se vere) f or all e x ce 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 P F   
•  
Ma xi m u m n u m ber of tr y ptase -p ositi ve mast cells per H P F 
•  
Acti ve i nfla m mati o n  
•  
C hr o nic i nfla m mati o n  
•  
I ntesti nal met a plasia 
•  
Atr o p h y 
•  
Reacti ve gastr o p at h y  
T he f oll o wi n g will be re p orte 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 P F   
•  
Ma xi m u m n u m ber of tr y ptase -p ositi ve mast cells per H P F   
•  
D u o de nal i ntrae pit helial l y m p h oc yt osis ( wit h c o u nts per 1 0 0 e nter o c yt es w h e n c o u nt is 
> 2 0) 
•  
Vill us arc hitect ure  


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 9 5  of 9 8  
C o nfi de nti al  
1 9. 6  A p pe n di x 6 : S a m ps o n’s Criteri a of A n a p h yl a xis 
S a m ps o n’s Criteri 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 yl a xis (cli nical defi niti o n) is t he ac ute o nset of 
ill ness ( 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 n eralize d hi ves, pr urit us or fl us hi n g, s w olle n li ps-t o n g ue u v ul a) 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 w a y c o m pr o mise (e. g., d ys p nea, w heeze, or br o n c h os pas m, stri d or, 
re d uce d P E F, h y p o x e mia) 
•  
CI R C U L A T O R Y : Re d u ce 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 n cti 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 n c h os pas m, stri d or 
a n d re d uce 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 o ciate d s y m pt o ms of e n d - or ga n 
d ysf u n cti 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 nal 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) 
 




Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 9 7  of 9 8  
C o nfi de nti al  
1 9. 8  A p pe n di x 8: Bi o m ar ker S u b -St u d y f or Selecte d Sites  
See La b or at or y Ma n ual S u b- St u d y M e m o  f or c o m plete i nstr ucti o ns f or c ollecti o n, pr ocessi n g, 
a n d s hi p pi n g of s u b-st u d y la b or at or y sa m ples. 
T he f oll o wi n g s a m ples ma y b e c ollecte d f or t he s u b -st u d y: 
Bl o o d S a m p les 
Plas ma fr o m w h ole bl o o d 
•  
C ollect 1 0 m L of bl o o d at Baseli ne a n d Da y 9 9 ( pri or t o E n d osc o p y). 
•  
Se n d fr oze n t o I C O N Ce ntral La b orat or y. 
Ser u m fr o m w h ole bl o o d 
•  
C ollect  1 0 m L of bl o o d at Baseli ne a n d Da y 9 9 ( pri or t o E n d osc o p y). 
•  
Se n d fr oze n t o I C O N Ce ntral La b orat or y . 
Uri ne S a m ples  
•  
C ollect at Baseli ne, Da y 9 9 ( pri or t o e n d osc o p y) a n d pre a n d p ost- d ose o n I nf usi o n Da ys 1, 
2 9, 5 7, a n d 8 5. 
•  
Se n d fr oze n t o I C O N Ce ntral La b orat or y. 
Bi o ps y S a m ples 
•  
C ollect 2 bi o psies fr o m a n a b n or mal- a p p eari n g area i n t he gastric m u c osa .  
•  
Se n d fr oze n t o I C O N Ce ntral La b orat or y. 
 


Pr ot oc ol A K 0 0 2 -0 0 3 
A me n d me nt 6 
Date:  0 7 Fe b 2 0 1 9  
Alla k os, I nc.  
P a ge 9 8  of 9 8  
C o nfi de nti al  
1 9. 9  A p pe n di x 9: A d diti o n al Q uesti o ns f or At o pic C o n diti o ns  
 

SAP_001.pdf: 
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the 
Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of AK002 in Patients with 
Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis 
NCT Number: NCT03496571 
Document Date: 29 May 2019 
 


 
 
Pa ge 1 of 3 5  
 
St atistic al A n al ysis Pl a n 
 
Pr ot oc ol Title 
A P hase 2, M ultice nter, Ra n d o mize d, D o u ble- Bli n d, 
Place b o- C o ntr olle d St u d y t o E val uate t he Efficac y, Safet y, T ole ra bilit y, 
a n d P har mac o d y na mic Effect of A K 0 0 2 i n Patie nts wit h E osi n o p hil ic 
Gastritis a n d/ or E osi n o p hilic Gastr oe nteritis 
Pr ot oc ol N u m ber 
A K 0 0 2- 0 0 3  
Pr ot oc ol Versi o n 
A me n d me nt 6 
Pr ot oc ol D ate 
Ori gi nal:  
1 1 A u g ust 2 0 1 7  
A me n d me nt 1:  
0 2 Marc h 2 0 1 8 
A me n d me nt 2:  
1 2 A pril 2 0 1 8 
A me n d me nt 3:  
7 Ma y 2 0 1 8 
A me n d me nt 4:  
2 3 A u g ust 2 0 1 8 
A me n d me nt 5. 1:  2 5 Se pte m ber 2 0 1 8 
A me n d me nt 6:   
0 7 Fe br uar y 2 0 1 9 
St u d y Dr u g 
A K 0 0 2 
St u d y P h ase 
2 
I N D N u m ber 
1 3 5 1 5 8 
S p o ns or  
Alla k os, I nc. 
9 7 5 Ocea n Dri ve, S uite 2 0 1 
Re d w o o d Cit y, C A 9 4 0 6 5 U S A 
S A P Versi o n 
2 
S A P D ate 
2 9 Ma y 2 0 1 9 
 
 
 






Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 3 of 3 5  
C o nfi de nti al  
T a ble of C o nte nts 
List of T a bles .................................................................................................................................. 5  
List of A b bre vi ati o ns ......................................... ............................................................................ 6 
Re visi o n Hist or y .............................................. ............................................................................... 8 
1.  
I ntr o d ucti o n .......................................................................................................................... 9 
2.  
St u d y O bjecti ves .............................................. ..................................................................... 9 
2. 1  
Pri mar y O bjecti ve ......................................................................................................... 9  
2. 2  
Sec o n dar y O bjecti ves ................................................................................................... 9  
2. 3  
E x pl orat or y O bjecti ves ................................................................................................. 9  
2. 4  
Safet y O bjecti ves ........................................................................................................ 1 0  
3.  
St u d y Desi g n ....................................................................................................................... 1 0  
3. 1  
Ge neral Descri pti o n ........................................... ......................................................... 1 0 
3. 2  
St u d y Treat me nt .......................................................................................................... 1 5  
3. 2. 1  
Treat me nt, D ose, a n d M o de of A d mi nistrati o n ................... ......................... 1 5 
3. 2. 2  
D urati o n of St u d y ............................................. ............................................ 1 5 
3. 2. 3  
Met h o ds of Assi g ni n g S u bjects t o Treat me nt Gr o u p .............. ..................... 1 5 
3. 3  
Bli n di n g ...................................................................................................................... 1 5  
3. 4  
H y p ot heses .................................................... .............................................................. 15  
3. 5  
Deter mi nati o n of Sa m pl e Size .................................. .................................................. 1 6 
3. 6  
C ha n ges t o A nal yses Pla n ne d i n t he Pr ot oc ol ................... ......................................... 1 6 
4.  
Defi niti o ns ................................................... ........................................................................ 1 6 
5.  
St u d y E n d p oi nts ............................................... .................................................................. 1 8 
5. 1  
Pri mar y Efficac y E n d p oi nt ..................................... .................................................... 1 8 
5. 2  
Sec o n dar y Efficac y E n d p oi nt ..................................................................................... 1 8  
5. 3  
E x pl orat or y E n d p oi nts ......................................... ....................................................... 1 9 
5. 4  
P har mac o ki netic ( P K) E n d p oi nts ................................ ............................................... 2 0 
5. 5  
Safet y E n d p oi nts .............................................. ........................................................... 2 0 
6.  
St atistic al Met h o ds ........................................... .................................................................. 2 1 
6. 1  
Ge neral Met h o d ol o g y ................................................................................................. 2 1  


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 4 of 3 5  
C o nfi de nti al  
6. 2  
Visit Wi n d o w a n d U nsc he d ule d Assess me nts ...................... ...................................... 2 2 
6. 3  
A dj ust me nt f or C o variates ..................................... ..................................................... 2 2 
6. 4  
Ha n dli n g of Dr o p o uts, Missi n g Dat a, a n d Data Discre pa ncies .... .............................. 2 2 
6. 5  
I nteri m A nal ysis .......................................................................................................... 2 3 
6. 6  
Ti mi n g of Fi nal A nal yses ...................................... ..................................................... 2 3 
6. 7  
M ultice nter St u d y ....................................................................................................... 2 3  
6. 8  
M ulti ple C o m paris o ns/ M ulti plicit y A dj ust me nt .................. ....................................... 2 3 
6. 9  
E xa mi nati o n of S u b gr o u ps ...................................... ................................................... 2 4 
7.  
St atistic al A n al ysis .......................................... .................................................................... 2 4 
7. 1  
A nal ysis P o p ulati o ns .................................................................................................. 2 4  
7. 1. 1  
Safet y P o p ulati o n ............................................. ............................................ 2 4 
7. 1. 2  
Per Pr ot oc ol A nal ysis ( P P) p o p ulati o n ......................... ................................ 2 4 
7. 2  
Dis p ositi o n of S u bjects ....................................... ........................................................ 2 5 
7. 3  
Pr ot oc ol De viati o ns .................................................................................................... 2 5  
7. 4  
De m o gra p hics a n d Baseli ne S u bject C haracteristics .................................................. 2 6  
7. 5  
Baseli ne Disease C haracteristics .............................. .................................................. 2 6 
7. 6  
Me dical Hist or y ............................................... ........................................................... 2 6 
7. 7  
E C G ............................................................................................................................ 2 6  
7. 8  
Pre g na nc y Test ............................................................................................................ 2 6  
7. 9  
Treat me nts .................................................... .............................................................. 26  
7. 9. 1  
Treat me nt C o m plia nce a n d E xte nt of E x p os ure ................... ....................... 2 6 
7. 9. 2  
Pri or a n d C o nc o mita nt Me dicati o ns ............................. ................................ 2 7 
7. 1 0   A nal ysis of Pri mar y Efficac y E n d p oi nt ......................... ............................................. 2 7 
7. 1 0. 1  
Pri mar y A nal ysis of Pri mar y Efficac y E n d p oi nt ................. ......................... 2 7 
7. 1 0. 2  
Sec o n dar y A nal ysis of Pri mar y Efficac y E n d p oi nt ............... ....................... 2 8 
7. 1 0. 3  
Se nsiti vit y A nal yses of Pri mar y Efficac y E n d p oi nt ............. ........................ 2 8 
7. 1 1   A nal ysis of Sec o n dar y Efficac y E n d p oi nts ................................................................ 2 9  
7. 1 1. 1  
Treat me nt Res p o n der at E n d of St u d y Treat me nt ................. ....................... 2 9 
7. 1 1. 2  
Patie nt Re p orte d O utc o me – T S S at E n d of St u d y Treat me nt ...... ............... 2 9 
7. 1 2   A nal ysis of E x pl orat or y E n d p oi nts ............................. ................................................ 2 9 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 5 of 3 5  
C o nfi de nti al  
7. 1 3   A nal ysis of P har mac o ki netic E n d p oi nt .......................... ............................................ 3 1 
7. 1 4   Safet y A nal yses ............................................... ........................................................... 3 2 
7. 1 4. 1  
A d verse E ve nts ............................................................................................. 3 2  
7. 1 4. 2  
La b orat or y Test ............................................... ............................................. 3 3 
7. 1 4. 3  
Vital Si g ns, Hei g ht a n d Wei g ht , a n d Ot her Safet y Meas ures ...................... 3 3 
7. 1 4. 4  
P h ysical E xa mi nati o n .......................................... ......................................... 3 4 
7. 1 4. 5  
A nal ysis of A nti- Dr u g A nti b o d y ................................ .................................. 3 4 
8.  
V ali d ati o n .................................................... ........................................................................ 3 4 
9.  
Refere nces ........................................................................................................................... 3 5  
 
 
List of T a bles 
Ta ble 1  
Sc he d ule of Assess me nts ....................................... ..................................................... 1 1 
Ta ble 2  
Ter mi n ol o g y a n d Defi niti o ns ................................... ................................................... 1 6 
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 6 of 3 5  
C o nfi de nti al  
List of A b bre vi ati o ns  
A E 
A d verse e ve nt 
A N C O V A  
A nal ysis of c o varia nce 
A D A  
A nti- dr u g a nti b o d y 
A T C  
A nat o mical T hera pe utic C he mical Classificati o n S yste m 
B MI 
B o d y mass i n de x 
B P 
B o dil y Pai n 
C B C  
C o m plete bl o o d c o u nt 
C M H  
C oc hra n- Ma ntel- Hae nszel 
C R F 
Case Re p ort F or m 
C R O  
C o ntract Researc h Or ga nizati o n 
C SI 
C o m p osite Sc ore of I nterest 
C S R 
Cli nical st u d y re p ort 
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts 
E C G  
Electr ocar di o gra m 
e C R F  
Electr o nic Case Re p ort F or m 
E D C  
Electr o nic Data Ca pt ure (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 E 
E osi n o p hilic es o p ha gitis 
E T 
Earl y Ter mi nati o n 
F D A  
F o o d a n d Dr u g A d mi nistrati o n 
F S H 
F ollicle- Sti m ulati n g H or m o ne 
G H 
Ge neral Healt h 
H P F 
Hi g h p o wer fiel d 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I C F 
I nf or me d C o nse nt F or m 
I V 
I ntra ve n o us  
M C S  
Me ntal C o m p o ne nt S u m mar y  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
MI T T  
M o difie d I nte nti o n-t o- Treat ( p o p ulati o n) 
M H 
Me ntal Healt h  
M M R M  
Mi xe d M o del f or Re peate d Meas ures 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 7 of 3 5  
C o nfi de nti al  
P C S 
P h ysical C o m p o ne nt S u m mar y 
P D 
P har mac o d y na mics 
PI D 
Patie nt I de ntificati o n ( n u m ber) 
P E 
P h ysical e xa mi nati o n 
P F 
P h ysical F u ncti o ni n g  
P K 
P har mac o ki netic(s) 
P T 
Preferre d ter m 
P R O  
Patie nt-re p orte d o utc o me 
p- val ue  
Pr o ba bilit y val ue 
Q o L 
Q ualit y of Life 
R E 
R ole- E m oti o nal 
R P 
R ole- P h ysical  
S A E 
Seri o us a d verse e ve nt 
S D 
Sta n dar d de viati o n 
S A P 
Statistical A nal ysis Pla n 
S F 
S ocial F u ncti o ni n g 
 
 
S O C  
S yste m or ga n class 
T E A E  
Treat me nt-e mer ge nt a d verse e ve nt 
T E A E SI  
Treat me nt-e mer ge nt a d verse e ve nt of si g nifica nt i nterest  
T E S A E  
Treat me nt-e mer ge nt seri o us a d verse e ve nt 
T L F 
Ta bles, Listi n gs, a n d Fi g ures 
T S S 
T otal S y m pt o m Sc ore 
V T 
Vitalit y  
W H O  
W orl d Healt h Or ga nizati o n 
W H O D D  
W orl d Healt h Or ga n izati o n Dr u g Dicti o nar y 
 
 
 
 
 




Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 9 of 3 5  
C o nfi de nti al  
1.  
I ntr o d ucti o n 
T his statistical a nal ysis pla n ( S A P) descri bes t he r ules a n d c o n ve nti o ns t o be use d i n t he a nal ysis 
a n d  prese ntati o n  of  efficac y,  safe t y, t olera bilit y, a n d p har maco d y na mic data as pla n ne d f or t he 
cli nical  pr ot oc ol.  It  descri bes t he  data  a n d  varia bles  t o  be  s um marize d  or  a nal yze d,  i ncl u di n g 
s pecificati o ns  of  t he  a nal ytical  met h o ds  t o  be  perf or me d.  T he  SA P  prese nte d  i n  t his  d oc u me nt 
s u perse des  t he  statistical  a nal ysis  met h o ds  descri be d  i n  t he  cl i nical  pr ot oc ol.  Si g nifica nt 
de viati o ns/c ha n ges  fr o m  t he  pla n ne d  a nal yses  descri be d  i n  t his S A P  will  be  i de ntifie d,  wit h 
j ustificati o n, i n t he a p pr o priate secti o n of t he cli nical st u d y re p ort ( C S R). T his S A P is base d o n 
t he cli nical st u d y pr ot oc ol A K0 0 2- 0 0 3 A me n d me nt 6, date d 0 7 Fe b r uar y 2 0 1 9, a n d its ass ociate d 
electr o nic case re p ort f or ms (e C R F).  
2.  
St u d y O bjecti ves  
2. 1  
Pri m ar y O bjecti ve 
T he pri mar y o bjecti ves of t he st u d y are t o e val uate: 
1)  
T he efficac y of A K 0 0 2 i n patie nts wit h E G a n d/ or E G E as esti mate d b y t he n u m ber of 
e osi n o p hils per H P F i n gastric bi o p sies bef ore a n d after recei vi n g A K 0 0 2 or place b o. 
2)  
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 G E.  
2. 2  
Sec o n d ar y O bjecti ves 
T he  sec o n dar y  o bjecti ves  are  t o e val uate  preli mi naril y  t he  effe cts  of  A K 0 0 2  i n  patie nts  wit h 
E G a n d/ or E G E b y c o m pari n g A K 0 0 2 t o pl ace b o treat me nt f or t he f oll o wi n g para meters: 
1)  
C o m pare treat me nt res p o n ders bet wee n A K 0 0 2 a n d place b o; a re s p o n der is a patie nt 
w h o  e x hi bit  a  > 3 0 %  re d ucti o n  i n  T otal  S y m pt o m  Sc ore  ( T S S)  (all P R O  s y m pt o ms) 
a n d a > 7 5 % re d ucti o n i n m uc osal e osi n o p hils. 
2)  
C ha n ges i n E G/ E G E s y m pt o ms i n a Patie nt Re p orte d O utc o me ( P R O) q uesti o n naire. 
2. 3  
E x pl or at or y O bjecti ves 
T he e x pl orat or y o bjecti ves are t o e val uate t he effect of A K 0 0 2 i n patie nts wit h E G a n d/ or E G E 
b y c o m pari n g A K 0 0 2 t o place b o treat me nt f or t he f oll o wi n g para m eters:  
1)  
C ha n ge i n 
. 
2)  
C ha n ges  i n 
  i n  a  Patie nt  Re p orte d O utc o me  ( P R O) 
q uesti o n naire. 
3)  
N u m ber  of 
 i n  patie nts  wit h 
 
. 
4) 
 bef ore a n d after treat me nt. 
5)  
C ha n ge  i n 
, 
res pecti vel y. 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 0 of 3 5  
C o nfi de nti al  
6)  
C ha n ge i n  
. 
7)  
C ha n ge i n 
 a n d 
 
  
8)  
Sc ori n g of 
 usi n g t he 
 
 
2. 4  
S afet y O bjecti ves 
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 G E b y deter mi ni n g 
A E i nci de nce a n d se verit y, st u d y wit h dra wals d ue t o A Es, c ha n ge s i n vital si g ns a n d la b orat or y 
tests  i ncl u di n g  i m m u n o ge nicit y, c ha n ges i n  c o nc o mita nt me dicati o n  use  d ue  t o  A Es,  a n d  ot her 
safet y para meters. 
3.  
St u d y Desi g n 
3. 1  
Ge ner al Descri pti o n 
T his  is  a  P hase  2,  m ulti-ce nter,  ra n d o mize d,  d o u ble- bli n d, plac e b o-c o ntr olle d  st u d y.  T he  st u d y 
c o m prises a scree ni n g peri o d of 2 1 t o 3 5 da ys wit h baseli ne e va l uati o ns f or st u d y eli gi bilit y. If 
s u bjects meet hist ol o g y a n d s y m pt om eli gi bilit y criteria, t he y will recei ve 4 d oses of A K 0 0 2 or 
place b o b y I V i nf usi o n o n Da ys 1, 2 9, 5 7, a n d 8 5. S u bjects will  be f oll o we d f or 5 6 da ys after last 
d ose. F oll o w- u p visits will occ ur o n Da ys 1 1 3 a n d 1 4 1.  
If t he a bs ol ute l y m p h oc yte or eosi n o p hil c o u nts ha ve n ot rec o ve re d b y Da y 1 4 1, t he f oll o w- u p 
peri o d will be e xte n de d, a n d s u bjects will be f oll o we d u ntil t h e c o u nts ha ve rec o vere d. D uri n g 
t he  e xte n de d  f oll o w- u p  peri o d,  s u bjects  will  ret ur n  t o  t he  site  e ver y  2 8  da ys  f or  a  f oll o w- u p 
safet y visit. 
T otal st u d y d urati o n will be u p t o a p pr o xi matel y 2 3 – 2 5 wee ks.  
T he st u d y desi g n is prese n te d sc he maticall y i n Ta ble 1 . 
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 1 of 3 5  
C o nfi de nti al  
T a ble 1  
Sc he d ule of Assess me nts 
Assess me nts  
Visits  
Scree ni n g  
( U p t o 5 
Wee ks)  
Tre at me nt Peri o d 
( 1 2 Wee ks) 
P ost- Tre at me nt F oll o w- u p Peri o d 
( 8 Wee ks) 
E xte n de d 
F oll o w- u p 
(if nee de d) 
B aseli ne 1 
D a y  11 
D a y 4 
( ± 1 d a y) 
D a y 1 5  
( ± 2 d a ys) 
D a y 2 9 
( ± 3 d a ys) 
D a y 5 7 
( ± 3 d a ys) 
D a y 8 5 
( ± 3 d a ys) 
D a y 9 9 
( ± 3 d a ys) 
D a y 1 1 3 
( ± 3 d a ys) 
D a y 1 4 1 
( ± 3 d a ys) 
or E T 3 0 
E ver y 
2 8 D a ys 3 2  
( ± 3 d a ys) 
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
 
De m o g ra p hics 
X 
 
 
 
 
 
 
 
 
 
 
Me dical Hist or y  
X 
X 
 
 
 
 
 
 
 
 
 
Pri or/c o nc o mita nt Me dicati o ns  
X  
X  
  
X  
X  
X  
X  
X  
X  
X  
 
B o d y  weig ht a n d hei g h t2  
X  
X  
  
X  
X  
X  
X  
  
X  
X  
 
Vital Si g ns 3 
X  
X  
  
X  
X  
X  
X  
  
X  
X  
 
1 2-lea d E C G 4 
X 
 
 
 
 
 
 
 
 
 
 
C o m plete P h y sical E xa mi nati o n5 
X 
 
 
 
 
 
 
 
 
 
 
Baseli ne Diet Assess me n t6 
 
X 
 
 
 
 
 
 
 
 
 
 
Baseli ne Diet C o m plia nce 7  
  
X  
  
X  
X  
X  
X  
X  
X  
X  
 
St o ol f or O va a n d Parasite 8, 1 2 
 
X 
 
 
 
 
 
 
 
 
 
 
e P R O Acti vati o n a n d Trai ni ng 9  
X 
 
 
 
 
 
 
 
 
 
 
e P R O Q uesti o n naire 1 0  
<----------------------- Perf or m D AI L Y fr o m Scree ni n g  t hr o ug h Da y  1 4 1 or 2 8 day s after last d ose if E T----------------------- >  
 
1 1  
X  
X  ( pre- d ose) 
 
 
 
X ( pre- d ose) 
X ( pre- d ose) 
X ( pre- d ose)  
  
X  
X  
 
E G D wit h Bi o ps y 1 2, 1 3 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
1 4 
X 
 
 
 
 
 
 
X 
 
 
 
 
Ser u m Pre g na nc y  test & F S H1 2, 1 5 
X  
 
 
 
 
 
 
 
 
 
 
 
Uri ne Pre g na nc y  test1 6 
 
X  ( pre- d ose) 
 
 
 
X ( pre- d ose) 
X ( pre- d ose) 
X ( pre- d ose) 
 
 
 
 
X 
 
 
Eli g i bility  Assess me nt 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
Stratificati o n a n d Ra n d o mizati o n 1 7   
 
X ( pre- d ose) 
 
 
 
 
 
 
 
 
 
 
Access I R T-e nter PI D a n d s u bject 
wei g h t 
 
X ( pre- d ose) 
 
 
 
X ( pre- d ose) 
X ( pre- d ose) 
X ( pre- d ose) 
 
 
 
 
 
 
 
Access I R T f or first s u bject 
scree ne d t o trig g er first I P s hi p me nt 
X 
 
 
 
 
 
 
 
 
 
 
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 2 of 3 5  
C o nfi de nti al  
T a ble 1  
Sc he d ule of Assess me nts c o nt. 
Assess me nts  
Visits  
Scree ni n g  
( U p t o 5 
Wee ks)  
Tre at me nt Peri o d 
( 1 2 Wee ks) 
P ost- Tre at me nt F oll o w- u p Peri o d 
( 8 Wee ks) 
E xte n de d 
F oll o w- u p 
(if nee de d) 
B aseli ne 1 
D a y 1 1 
D a y 4 
( ± 1 d a y) 
D a y 1 5  
( ± 2 d a ys) 
D a y 2 9 
( ± 3 d a ys) 
D a y 5 7 
( ± 3 d a ys) 
D a y 8 5 
( ± 3 d a ys) 
D a y 9 9 
( ± 3 d a ys) 
D a y 1 1 3 
( ± 3 d a ys) 
D a y 1 4 1 ( ± 3 
d a ys) or 
E T 3 0 
E ver y 
2 8 D a ys 3 2 
( ± 3 d a ys) 
Pre me dicati o n wit h cetirizi ne a n d 
aceta mi n o p he n or a p pr o ve d 
alter nati ve 1 8 
 
X  ( pre- d ose) 
 
 
X  ( pre- d ose) 
X  ( pre- d ose) 
X  ( pre- d ose) 
 
 
 
 
 
 
 
St u d y  dr ug  a d mi nistrati o n1 9 
 
X 
 
 
X  
X  
X  
  
  
 
 
S y m pt o m - directe d P h ysical E xam 2 0  
  
X  
  
X  
X  
X  
X  
  
X  
X  
 
C B C wit h differe ntial 1 2, 2 1 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
C he mistr y 1 2, 2 2 
X 
X  ( pre- d ose) 
 
 
X 
X ( pre- d ose) 
X ( pre- d ose) 
X ( pre- d ose)  
  
X  
X  
 
Uri nal ysis 1 2, 2 3 
X 
X  ( pre- d ose) 
 
 
 
X ( pre- d ose) 
X ( pre- d ose) 
X ( pre- d ose)  
  
X  
X  
 
Ser ol o g y 1 2, 2 4 
X 
 
 
 
 
 
 
 
 
 
 
 
Bl o o d f or e x pl orat or y safet y 
a naly sis (if i n dicate d)1 2, 2 5 
 
X 
 
 
 
X 
X 
X 
 
 
 
 
 
 
 
Bl o o d f or hista mi ne a n d tr y ptase (if 
i n dicated )1 2, 2 5 
 
X 
 
 
 
X 
X 
X 
 
 
 
 
 
 
 
Bl o o d f or P K a n d st ora ge 1 2, 2 6 
X 
 
 
X 
X ( pre- d ose) 
X ( pre- d ose) 
X ( pre- d ose)  
  
X  
X  
 
Bl o o d f or E x pl orat or y  A naly sis1 2, 2 7 
 
X ( pre- d ose) 
 
 
 
X ( pre- d ose) 
 
X ( pre- d ose) 
 
 
 
 
X 
 
 
Bl o o d f or A D A 1 2, 2 8 
X 
 
 
X 
X  ( pre- d ose) 
X ( pre- d ose) 
X ( pre- d ose) 
 
 
 
 
X 
 
 
Bl o o d f or T otal Ser u m I g E 1 3, 2 9 
 
X ( pre- d ose) 
 
 
 
 
 
 
 
X 
 
N o n-seri o us A d verse E ve nts 
 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
A d verse E ve nts of S pecial I nteres t 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
Seri o us A d verse E ve nts 3 1 
X  
X  
  
X  
X  
X  
X  
X  
X  
X  
X 
Be gi n A K 0 0 2- 0 0 3 X e xte nsi o n st u d y 
(if a p plica ble)3 3 
 
 
 
 
 
 
 
 
X 
 
 
 
A D A:  A nti- A K 0 0 2 a nti b o d y 
E T:  
Earl y Ter mi nati o n 
C B C:  C o m plete bl o o d c o u nt 
F S H:  F ollicle-sti m ulati n g h or m o ne 
E C G:  Electr ocar di o gra m 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 3 of 3 5  
C o nfi de nti al  
T a ble 1 N otes 
1)  
Baseli ne scree ni n g visit ca n o cc ur o ver se veral  da ys wit hi n t he scree ni n g peri o d. Da y 1 can be gi n as s o o n as eli gi bilit y cr iteria are met. 
2)  
At scree ni n g, hei g ht (i n c m)  a n d wei g ht (i n k g) will be rec or de d. B o d y wei g ht will als o be measure d o n Da ys 1, 1 5, 2 9, 5 7, 8 5, a n d o n f oll o w- u p Da ys 1 1 3 a n d 1 4 1 or E T. 
3)  
Vital si g ns will be meas ure d at scree ni n g, Da ys 1 5, 9 9, 1 1 3,  1 4 1 or E T a n d o n all d osi n g da ys pre- d ose, 1 5 mi n utes ( ± 5 mi n utes) after t he start of st u d y dr u g i nf usi o n, 
i m me diatel y f oll o wi n g t he e n d of i nf usi o n o n treat me nt da ys ( + 5 mi n utes), 1 h o ur ( ± 1 5 mi n utes) i nt o t he p ost-i nf usi o n o bser vati o n peri o d a n d j ust pri or t o disc har ge. 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 be meas ure d after t he s u bject has bee n at rest f or > 5 mi n utes a n d 
bef ore a n y bl o o d dra w.  
4)  
A n E C G will be o btai ne d at scr ee ni n g bef ore a n y bl o o d is dra w n a n d after t he s u bject has bee n i n t he s u pi ne p ositi o n f or ≥5  mi n utes. 
5)  
A c o m plete p h ysical e xa mi nati o n will be perf or me d b y eit her t he I n vesti gat or or desi g nee a n d i ncl u de t he f oll o wi n g b o d y s yste m or or ga n assess me nts: s ki n; hea d, e yes, ears, 
n ose a n d t hr oat; t h yr oi d; l u n gs; car di o vasc ular; a b d o me n; e xtre mities; l y m p h n o des; a n d a brief ne ur ol o gical e xa mi nati o n. 
6)  
A Baseli ne Diet Assess me nt will be perf or me d usi n g sta n dar di ze d q uesti o ns. Eati n g patter ns, f o o d a v oi da nce be ha vi ors, a n d a ller gies will be ca pt ure d. 
7)  
A Baseli ne Diet C o m plia nce c hec k will be perf or me d a n d a n y v aria nces fr o m t he baseli ne diet  d oc u me nte d. S u bjects s h o ul d tr y t o mai ntai n t he baseli ne diet as m uc h as 
p ossi ble t hr o u g h o ut t he st u d y. 
8)  
Fecal c ollecti o n kits f or O va a n d Parasite test will be pr o v i de d t o s u bjects at scree ni n g. C ollecti o n kits s h o ul d be ret ur ne d t o t he cli nical site wit hi n 1 da y of c ollecti o n. 
9)  
Acti vate E G/ E G E P R O q uesti o n n aire a n d pr o vi de s u bject wit h u ni q ue user na me a n d pass w or d. E G/ E G E P R O q uesti o n naire s h o ul d be  acti vate d f or all s u bjects. S u bjects wit h 
c o nc o mita nt hist or y of at o pic ast h ma, at o pic der matitis a n d/ or e osi n o p hilic es o p ha gitis  will recei ve a n e xtra q uesti o n, a b o ut eac h, as a p pr o priate. 
1 0)  E G/ E G E P R O s h o ul d be c o m plete d ar o u n d t he sa me ti me eac h da y. Pri or t o e nr oll me nt, t he E G/ E G E P R O wee kl y a vera ges o ver t he  scree ni n g peri o d will be calc ulate d a n d 
use d t o assess eli gi bilit y a n d esta blis h t he baseli ne se verit y of s y m pt o ms.  
1 1)  T o be c o m plete d b y s u bject, i n cli nic, pri or t o a n y bl o o d d ra w, p h ysical e xa m, or vital si g n meas ure me nts. 
1 2)  S peci me n pr ocesse d b y ce ntral  la b. See ce ntral la b orat or y ma n ual f or c ollecti o n a n d pr ocessi n g details. 
1 3)  See Pr ot oc ol A p pe n di x 5 f or bi o ps y assess me nts. T he p ost-tr eat me nt e n d osc o p y ( E G D) a n d bi o ps y assess me nts will be perf or me d o n Da y 9 9 ( ± 3) a n d b i o ps y res ults will be 
bli n de d. 
1 4)  T o be perf or me d d uri n g t he c o n d uct of t he E G D d uri n g t he sc ree ni n g peri o d a n d o n D 9 9. 
1 5)  Bl o o d f or ser u m pre g na nc y a n d F S H will be c ollecte d o n scree ni n g, f or s u bjects of c hil d beari n g a bilit y or t o s h o w p ost- me n o pa usal stat us. 
1 6)  Uri ne f or uri ne pre g na nc y te st will be c ollecte d pre- d ose on all i nf usi o n da ys a n d at E O S . Test kits will be s u p plie d b y the ce ntral la b. Tests will be c o m plete d o n site a n d 
e val uate d pri or t o i nf usi o n(s). 
1 7)  Stratificati o n base d o n hi g hest wee kl y s y m pt o m a vera ge rec o r de d ( gr o u p of 3. 0 – 4. 9 or 5. 0 – 1 0. 0). Ra n d o mizati o n a n d stratificati o n will occ ur t hr o u g h Ce n d uit I R T. 
1 8)  Pre me dicati o n re q uire d pri or t o first a n d sec o n d i nf usi o ns a n d at t he I n vesti gat or’s discreti o n f or t hir d a n d f o urt h i nf us i o ns, de pe n di n g o n t olera nce of pri or i nf usi o ns.  


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 4 of 3 5  
C o nfi de nti al  
1 9)  St u d y dr u g will be a d mi nistere d as a si n gle peri p heral I V i nf usi o n o ver at least 5 h o urs o n st u d y Da y 1 a n d at least 4 h o u rs o n Da y 2 9 ( ± 3 da ys) a n d Da y 5 7 ( ± 3 da ys). T he 
i nf usi o n ma y be s h orte ne d t o 3 – 5 h o urs f or Da y 8 5 ( ± 3 da ys). Please refer t o t he P har mac y Ma n ual f or detaile d i nstr ucti o ns o n st u d y dr u g pre parati o ns, a d mi nistrati o n, a n d 
i nf usi o n rates. 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 of st u d y dr u g. 
2 0)  A s y m pt o m- directe d P E (i ncl u di n g assess me nt of p ossi ble i nf usi o n site reacti o ns) will be perf or me d b y t he I n vesti gat or or desi g nee, as nee de d if a n y s y m pt o ms are re p orte d. 
2 1)  Bl o o d f or C B C wit h differe ntial, i ncl u di n g a bs ol ute 
 a n d bas o p hil c o u nts, will be o btai ne d j ust pri or t o eac h i nf usi o n, 1 h o ur after t he e n d of eac h i nf usi o n, 
4 h o urs after t he e n d of i nf usi o n 1, as well as d uri n g t he scre e ni n g peri o d a n d o n Da ys 4, 1 5, 9 9, 1 1 3, a n d 1 4 1 or E T a n d E xte n de d F oll o w- U p, if a p pli ca ble. All differe ntial 
bl o o d c o u nts fr o m Da y 1 ( p ost- d o se) a n d pri or t o Da y 1 4 1 or Earl y Ter mi nati o n will be bli n de d t o t he S p o ns or a n d t he site. A n u nsc he d ule d C B C ma y be c ollecte d at t he 
re q uest of t he u n bli n de d safet y mo nit or. Differe ntial bl o o d c o u nts will n ot be bli n de d at t he Da y  1 4 1/ E T visit a n d t hese res ults will be use d b y t he site t o deter mi ne if t he 
s u bject nee ds t o e nter t he E xte n de d F oll o w- U p peri o d.  
2 2)  Bl o o d f or c he mistr y will be o btai ne d pre- d ose o n d osi n g Da y s 1, 2 9, 5 7, a n d 8 5, as well as d uri n g t he scree ni n g peri o d a n d  o n Da y 1 5, Da y 1 1 3, a n d Da y 1 4 1 or E T. 
2 3)  Uri ne f or sta n dar d uri nal ysi s will be o btai ne d pre- d ose o n d osi n g Da ys 1, 2 9, 5 7, a n d 8 5, as well as d uri n g t he scree ni n g peri o d a n d o n Da y 1 1 3 a n d Da y 1 4 1 or E T. 
2 4)  Ser ol o g y will i ncl u de H Bs A g , he patitis C a nti b o d y, a nti- H Bc, a n d HI V. 
2 5)  If a n I nf usi o n-relate d reacti o n ca uses a n i nf usi o n i nterr u p ti o n or cessati o n a sa m ple of bl o o d s h o ul d be o btai ne d f or e x plorat or y safet y a nal ysis wit hi n 1 – 2 h o urs of t he o nset 
of t he s y m pt o ms. A sa m ple of bl o o d s h o ul d be o btai ne d f or testi n g of hista mi ne a n d tr y ptase le vels wit hi n 1 – 2 h o urs, if a na p h y la xis is s us pecte d. 
2 6)  Bl o o d f or P K s h o ul d be o btai ne d pre- d ose o n d osi n g Da ys 2 9,  5 7, a n d 8 5, as well as d uri n g scree ni n g a n d o n Da ys 1 5, 1 1 3, an d 1 4 1 or E T.  
2 7)  Bl o o d sa m ples f or e x pl orat or y a nal ysis will be c ollecte d pr e- d ose o n Da ys 1, 2 9, a n d 8 5 a n d als o o n Da y 1 4 1 or E T.  
2 8)  Bl o o d sa m ples f or A D A will be  c ollecte d d uri n g t he scree ni ng peri o d, o n Da ys 1 5, 2 9, 5 7, 8 5 a n d Da y 1 4 1 or E T a n d a n yti me a n i m m u n o ge nicit y-relate d A E occ urs. 
2 9)  Bl o o d sa m ples f or T otal Ser u m I g E will be c ollecte d o n Da y 1 a n d o n Da y 1 4 1 or E T. 
3 0)  T he E T Visit s h o ul d be c o n d uct e d 2 8 ( ± 3) da ys after t he las t d ose of st u d y dru 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 earl y ter mi nati o n occ urs 
m ore t ha n 2 8 da ys after t he last d ose of st u d y dr u g, t he n perf o r m t he E T visit as s o o n as p ossi ble. T he pr oce d ures liste d u n der t he fi nal f oll o w- u p visit will be c o n d ucte d 
u nless directe d ot her wise  b y t he Me dical M o nit or. 
3 1)  T he re p orti n g of Seri o us A d verse E ve nts occ urri n g after si g ni n g I nf or me d c o nse nt a n d pri or t o t he first i nf usi o n will be l i mite d t o t h ose t hat relate t o scree ni n g pr oce d ures. 
T he ca pt ure of all ot her S A Es a n d A d verse E ve nts t hat are n ot S A Es will be gi n at t he ti me of f irst i nf usi o n of st u d y dr u g. 
3 2)  E xte n de d f oll o w- u p, if nee de d, e ver y 2 8 da ys ( ± 3 da ys) u nti l e osi n o p hil a n d/ or l y m p h oc yte c o u nts ha ve rec o vere d.  
3 3)  S u bjects w h o si g n t he i nf or me d c o nse nt f or t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y will c o m plete t he p r oce d ures f or Da y 1 1 3 a n d t hen i m me diatel y be gi n o pe n-la bel d osi n g i n t he 
e xte nsi o n st u d y if eli gi ble. S u bj ects will n ot c o m plete t he Da y 1 4 1 pr oce d ures or e xte n de d f oll o w- u p u n der t he A K 0 0 2- 0 0 3 pr ot oc ol. O pe n-la bel d osi n g a n d f oll o w- u p 
i ncl u di n g a n y e xte n de d f oll o w- u p re q uire d t o m o nit or t he rec o ver y of l y m p h oc ytes a n d e osi n o p hils will occ ur u n der t he A K 0 0 2- 0 03 X e xte nsi o n pr ot oc ol. 
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 5 of 3 5  
C o nfi de nti al  
3. 2  
St u d y Tre at me nt 
3. 2. 1  Tre at me nt, D ose, a n d M o de of A d mi nistr ati o n 
 Treat me nt Gr o u p 1: 0. 3 m g/ k g A K 0 0 2 o n Da y 1 f oll o we d b y 1 m g/ k g  o n Da y 2 9, f oll o we d 
b y 3 m g/ k g o n Da ys 5 7, a n d 8 5 
 Treat me nt  Gr o u p  2:  0. 3  m g/ k g  A K 0 0 2  o n  Da y  1  f oll o we d  b y  1  m g/ k g   o n  Da ys  2 9,  5 7, 
a n d 8 5 
 Treat me nt Gr o u p 3: Place b o o n Da ys 1, 2 9, 5 7, a n d 8 5 
3. 2. 2  D ur ati o n of St u d y 
T otal s u bject d urati o n o n st u d y is a p pr o xi matel y 2 3 – 2 5 wee ks.  
 Scree ni n g p hase: 2 1 – 3 5 da ys  
 Treat me nt p hase: 8 5 da ys ( ± 3 da ys)  
 F oll o w- u p after last d ose: 5 6 f or s u bjects w h o d o n ot e nr oll i n  t he A K 0 0 2- 0 0 3 X e xte nsi o n 
st u d y or 2 8 da ys ( ± 3 da ys) f or s u bjects w h o e nr oll i n t he A K 0 0 2 - 0 0 3 X e xte nsi o n st u d y. If 
t he a bs ol ute l y m p h oc yte or e osin o p hil c o u nts ha ve n ot rec o vere d  b y Da y 1 4 1, t he f oll o w-
u p peri o d will be e xte n de d, a n d s u bj ects will be f oll o we d u ntil  t he c o u nts ha ve rec o vere d.  
3. 2. 3  Met h o ds of Assi g ni n g S u bjects t o Tre at me nt Gr o u p 
A p pr o xi matel y  6 0  s u bjects  will  be  stratifie d  base d  o n  t he  hi g hest  wee kl y  a vera ge  of  t he 
q ualif yi n g s y m pt o m of disease rec o r de d  o n t he P R O  q uesti o n naire d uri n g t he scree ni n g peri o d 
( P R O sc ore 3 – 4. 9, or 5. 0 – 1 0. 0) a n d ra n d o mize d i n a 1: 1: 1 rati o t o Treat me nt Gr o u ps 1, 2, a n d 3 
( Secti o n 3. 2. 1).  
3. 3  
Bli n di n g 
T his  is  a  d o u ble- bli n d  st u d y.  T he i de ntit y  of  test  a n d  place b o treat me nts  will  n ot  be  k n o w n  t o 
i n vesti gat ors, s p o ns or, researc h staff, s u bjects, or t he pri mary st u d y m o nit or. O nl y t he u n bli n de d 
st u d y p har macist, t he u n bli n de d p har mac y m o nit or a n d t he u n bli n de d safet y m o nit or will k n o w 
t he treat me nt assi g n me nt. 
3. 4  
H y p ot heses 
T he h y p ot hesis t o be teste d i n t he st u d y is t hat A K 0 0 2, i n eit h er o ne or b ot h of t he 2 d oses, are 
differe nt fr o m place b o wit h re gar d t o t he pri mar y e n d p oi nt of n u m ber of e osi n o p hils per H P F i n 
bi o psies fr o m t he gastric m uc osa. 
 
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 6 of 3 5  
C o nfi de nti al  
3. 5  
Deter mi n ati o n of S a m ple Size 
Ass u mi n g  a  re d ucti o n  of  3 0 %  i n  t h e  n u m ber  of  e osi n o p hils  per  H P F  ( pri mar y  e n d p oi nt)  fr o m 
baseli ne i n t he A K 0 0 2-treate d gr o u p ( Treat me nt Gr o u p 1 or 2) ve rs us a 1 0 % re d ucti o n per H P F 
i n  t he  place b o  gr o u p  ( Treat me nt  Gr o u p  3),  a n d  ass u mi n g  a  sta n dar d  de viati o n  of  2 0 %, 
2 0 s u bjects per gr o u p w o ul d pr o vi de  8 7 % p o wer wit h a si g nifica nce le vel of 0. 0 5.  
3. 6  
C h a n ges t o A n al yses Pl a n ne d i n t he Pr ot oc ol 
T he pr ot oc ol- defi ne d gate kee pi n g pr oce d ure of hi g h d ose t he n l o w d ose c o m paris o n t o place b o 
f or t he pri mar y e n d p oi nt is re vise d t o i ncl u de hi g h/l o w p o ole d, hi g h, a n d l o w d ose c o m paris o ns 
t o place b o f or t he pri mar y a n d sec o n dar y e n d p oi nts. 
T he  pr ot oc ol- defi ne d  treat me nt  r es p o n der  is  n o w  classifie d  as  t he  1 st  sec o n dar y  e n d p oi nt  a n d 
perce nt  c ha n ge  fr o m  baseli ne  t o e n d  of  treat me nt  i n  T S S  is  n o w t he  sec o n d  ( 2n d)  sec o n dar y 
e n d p oi nt.    Ot her  pr ot oc ol- defi ne d  sec o n dar y  e n d p oi nts  are  n o w  m o ve d  t o  t he  e x pl orat or y 
e n d p oi nts. 
T he pr ot oc ol- defi ne d MI T T p o p ulati o n is n o w re place d wit h Per Pr ot oc ol p o p ulati o n f or efficac y 
a nal ysis. 
4.  
Defi niti o ns  
T a ble 2  
Ter mi n ol o g y a n d Defi niti o ns 
 
Ter mi n ol o g y 
Defi niti o n 
St u d y Me dicati o n/ Dr u g 
( S M) 
A K 0 0 2 or place b o a d mi nistere d b y I V i nf usi o n. 
St u d y Da y 
St u d y Da y 1 is defi ne d as t he date o n w hic h a s u bject  t o o k t he first 
d ose of S M. Ot her st u d y da ys are  defi ne d relati ve t o St u d y Da y 1. 
F or visits pri or t o t he first d ose of t he S M, St u d y Da y is calc ulate d 
as Visit Date – Da y 1 Date. F or v isits after t he first d ose, Stu d y Da y 
is calc ulate d as Visit Date – Da y 1 Date + 1. 
E nr olle d 
S u bject w h o is ra n d o mize d t o a treat me nt gr o u p.  
C o m pleter f or t he St u d y  
S u bject w h o c o m pletes visits t hr o u g h t h e Da y 1 1 3 Visit a n d e nr olls 
i n t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y O R a s u bject w h o d oes n ot 
e nter t he A K 0 0 2- 0 0 3 X e xte nsi o n st u d y b ut c o m pletes t he Da y 1 4 1 
visit. 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 7 of 3 5  
C o nfi de nti al  
Ter mi n ol o g y 
Defi niti o n 
Baseli ne 
Baseli ne f or n o n- dail y a ssess me nt (e g, la b orat or y tests a n d  
) is 
defi ne d as t he n o n- missi n g val ue c ollecte d m ost rece nt t o a n d b ef ore 
t he ti me of t he ver y first d ose of t he st u d y dr u g.  Baseli ne f or dail y 
assess me nt (e g, e P R O) is defi ne d a s t he a vera ge of all assess ments 
pri or t o t he first d ose of t he  st u d y dr u g. Baseli ne f or bi o ps y res ults 
is f o u n d i n t he res pecti ve a nal ysis secti o n. 
Pri or Me dicati o n  
Me dicati o n c olle cte d o n t he Pri or/ C o nc o mita nt Me dicati o n C R F, 
wit h start date pri or t o St u d y Da y 1. 
C o nc o mita nt Me dicati o n  
Me dicati o n c ollecte d o n t h e Pri or/ C o nc o mita nt Me dicati o n C R F, 
wit h e n d date o n/after St u d y Da y 1. N ote a Pri or Me dicati o n ma y  
als o be a C o nc o mita nt Me dicati o n if t he start date is pri or t o St u d y 
Da y 1 a n d e n d date is o n/after St u d y Da y 1. 
Treat me nt-e mer ge nt  
A d verse e ve n ts re p orte d i n t he cli nical database 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 V i nf usi o n of 
t he S M.  
Patie nt Re p orte d O utc o me 
( P R O) 
P R O q uesti o n naire e val uates 8 d iffere nt s y m pt o ms wit h 1 0 dail y 
q uesti o ns f or i nte nsit y a n d fre q ue nc y: 
 A b d o mi nal pai n i nte nsit y 
 Na usea i nte nsit y 
 V o miti n g i nte nsit y 
 V o miti n g fre q ue nc y 
 Diarr hea i nte nsit y 
 Diarr hea fre q ue nc y 
 Earl y satiet y 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 
Eac h i nte nsit y e val uati o n is sc ore d o n a scale of 0 = n o ne t o 
1 0 = w orst p ossi ble. 
P R O T otal S y m pt o m 
Sc ore ( T S S) 
T S S is t he s u m of 8 (a b d o mi nal  pai n, a b d o mi nal cra m pi n g, bl oatin g, 
na usea, v o miti n g, diarr hea, earl y satiet y, a n d l oss of a p petite ) 
wee kl y a vera ge s y m pt o m i nte nsit y sc ores. 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 8 of 3 5  
C o nfi de nti al  
Ter mi n ol o g y 
Defi niti o n 
P R O C o m p osite Sc ore of 
I nterest ( C SI) 
C SI is t he s u m of t he 3 (a b d o mi nal pai n, na usea, a n d diarr hea) 
wee kl y a vera ge s y m pt o m i nte nsit y sc ores of s pecial i nterest. 
Treat me nt Res p o n der  
S u bject wit h > 3 0 % re d ucti o n i n T S S sc ore c o m bi ne d wit h a > 7 5 % 
re d ucti o n i n e osi n o p hils i n t he gastric a n d/ or d u o de nal m uc osa.  T he 
e osi n o p hil c o u nt is o btai ne d o n D a y 9 9 ( Wee k 1 4) bi o ps y a n d t he  
T S S sc ore f or t he a nal ysis will be t he a vera ge of t he 1 4 dail y sc ores 
starti n g wit h t he da y of t he last d ose t o t he da y bef ore t he e nd of 
st u d y bi o ps y.  If a mi ni m u m of 7 dail y sc ores are n ot rec or de d i n 
t his n o mi nal 1 4- da y wi n d o w, t he wi n d o w will be r olle d bac k u ntil a 
mi ni m u m of 7 sc ores are prese nt.  F or patie nts w h ose bi o ps y is 
c ollecte d pri or t o Da y 9 9 d ue t o earl y disc o nti n uati o n, t he a ve ra ge 
of t he last 1 4 da ys of T S S sc ores rec or de d f or t hat patie nt will be 
use d f or t he a nal ysis. 
St u d y Wee k 
St u d y Wee k f or P R O a nal ysis is defi ne d as 7 da ys a w ee k starti n g 
fr o m t he da y of first d ose ( Da y 1).  
 
5.  
St u d y E n d p oi nts 
5. 1  
Pri m ar y Effic ac y E n d p oi nt 
Perce nt c ha n ge fr o m baseli ne i n  t he n u m ber of e osi n o p hils per H P F i n gastric m uc osa or 
d u o de nal  m uc osa  at  Wee k  1 4  ( Da y  9 9).  F or  s u bjects  w h o  pr o vi de  b ot h  gastric  a n d 
d u o de nal  bi o psies,  t he  calc ulati o n  will  be  base d  o n  t he  a vera ge   c o u nt  of  t he  hi g hest 
rea di n gs  fr o m  t he  Da y  9 9/ E n d  of  st u d y  bi o ps y  t hat  c orres p o n d  i n  l ocati o n  ( gastric  or 
d u o de nal) t o t he l ocati o n wit h t he  hi g hest a vera ge c o u nt at baseli ne.  
5. 2  
Sec o n d ar y Effic ac y E n d p oi nt 
1st Sec o n dar y E n d p oi nt 
Pr o p orti o n  of  Treat me nt  Res p o n ders,  defi ne d  as  patie nts  wit h  > 3 0 %  re d ucti o n  i n  T S S 
sc ore  c o m bi ne d  wit h  a  > 7 5 %  re d ucti o n  i n  e osi n o p hils  i n  t he  gastric  a n d/ or  d u o de nal 
m uc osa. T he e osi n o p hil c o u nt is o btai ne d o n Da y 9 9 ( Wee k 1 4) bi o ps y a n d t he T S S sc ore 
f or t he a nal ysis will be t he a vera ge of t he 1 4 dail y sc ores starti n g wit h t he da y of t he last 
d ose t o t he da y bef ore t he e n d of st u d y bi o ps y.  If a mi ni m u m o f 7 dail y sc ores are n ot 
rec or de d  i n  t his  n o mi nal  1 4- da y  wi n d o w,  t he  wi n d o w  will  be  r olle d  bac k  u ntil  a 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 1 9 of 3 5  
C o nfi de nti al  
mi ni m u m of 7 sc ores are prese nt.  F or patie nts w h ose bi o ps y is c ollecte d pri or t o Da y 9 9 
d ue t o earl y disc o nti n uati o n, t he a vera ge of t he last 1 4 da ys o f T S S sc ores rec or de d f or 
t hat patie nt will be use d f or t he a nal ysis. 
2 n d Sec o n dar y E n d p oi nt 
Perce nt c ha n ge fr o m baseli ne i n t he T S S sc ores a vera ge d o ver t h e 1 4 dail y sc ores starti n g 
wit h  t he  da y  of  t he  last  d ose  t o  t he  da y  bef ore  t he  e n d  of  st u d y  bi o ps y.    F or  patie nts 
w h ose bi o ps y is c ollecte d pri or  t o Da y 9 9 d ue t o earl y disc o ntin uati o n, t he a vera ge of t he 
last 1 4 da ys of T S S sc ores rec or de d f or t hat patie nt will be use d f or t he a nal ysis. ( See 1 st 
Sec o n dar y E n d p oi nt f or t he cal c ulati o n of T S S a vera ge.) 
5. 3  
E x pl or at or y E n d p oi nts 
 C ha n ge fr o m baseli ne i n t he 
 c o u nts b y visit.  
 C ha n ge  fr o m  baseli ne  i n  t he 
  sc ores  a verage d  o ver  t he  1 4  dail y 
sc ores starti n g wit h t he da y of the last d ose t o t he da y bef ore  t he e n d of stu d y bi o ps y.  F or 
patie nts  w h ose  bi o ps y  is  c ollecte d  pri or  t o  Da y  9 9  d ue  t o  earl y   disc o nti n uati o n,  t he 
a vera ge  of  t he  last  1 4  da ys  of  sc ores  rec or de d  f or  t hat  patie nt   will  be  use d  f or  t he 
a nal ysis. ( See 1 st Sec o n dar y E n d p oi nt f or t he calc ulati o n of a vera ge.) 
 Perce nt c ha n ge fr o m baseli ne i n t he  
 sc ores a vera ge d o ver t he 1 4 dail y sc ores starti n g 
wit h t he da y of t he last d ose  t o t he da y bef ore t he e n d of st u dy bi o ps y.  F or patie nts 
w h ose bi o ps y is c ollecte d pri or t o Da y 9 9 d ue t o earl y disc o ntin uati o n, t he a vera ge of t he 
last 1 4 da ys of  
 sc ores rec or de d f or t hat patie nt will be use d f or t he a nal ysis. ( See 1 st 
Sec o n dar y E n d p oi nt f or t he calc u lati o n of  
 a vera ge.)   
 Perce nt  C ha n ge  fr o m  baseli ne  t o  Wee k  1 4  ( Da y  9 9)  i n  t he  n u m ber of 
 
 i n patie nts wit h 
. 
 Pr o p orti o n of  
o  E G patie nts wit h a vera ge 
 per H P F i n 
,  
o  E G E patie nts wit h a vera ge 
 per H P F i n 
, a n d  
o  E o E patie nts wit h a vera ge 
 per H P F i n 
 . 

 bef ore a n d after treat me nt. 
 C ha n ge fr o m baseli ne t o Wee k 1 4 ( Da y 9 9) i n t he n u m ber of 
 i n  
 
,  
 
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 0 of 3 5  
C o nfi de nti al  
 
. 
 C ha n ge fr o m baseli ne i n t he sc ori n g of 
 
usi n g t he 
. 
 C ha n ges fr o m baseli ne t o Wee k 1 4 ( Da y 9 9) i n  
  
 
 
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
  
 
. 
 C ha n ge fr o m baseli ne i n t he
 f or patie nts wit h 
 
 Perce nt c ha n ges fr o m baseli ne i n t he  
 a n d  
 f or a vera ges of Wee ks 1 3- 1 4, 1 1- 1 4 a n d 
Wee ks 9- 1 4 a n d se paratel y f or eac h i n di vi d ual wee k. 
 C ha n ges fr o m baseli ne i n t he 
 f or a vera ges of Wee ks 1 3- 1 4, 1 1-
1 4 a n d Wee ks 9- 1 4 a n d se paratel y f or eac h i n di vi d ual wee k. 
 C ha n ge fr o m baseli ne i n  
 o ver ti me. 

 at baseli ne a n d Da y 9 9. 
 Distri b uti o n of 
 i n t he hist olo gical fi n di n gs at Da y 9 9. 
5. 4  
P h ar m ac o ki netic ( P K) E n d p oi nts 
 Ser u m c o nce ntrati o ns of A K 0 0 2 pri or t o eac h d ose a n d o n Da ys 1 5 , 1 1 3 a n d 1 4 1 ( or E T). 
5. 5  
S afet y E n d p oi nts 
Safet y e n d p oi nts i ncl u de: 
 Treat me nt-e mer ge nt a d verse e ve nts ( T E A Es) 
 C ha n ge i n la b orat or y test res ul ts ( He mat ol o g y, Bl o o d c he mistr y, Uri nal ysis) 
 C ha n ges i n vital si g ns 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 1 of 3 5  
C o nfi de nti al  
 P h ysical e xa mi nati o n 
 A nti- dr u g ( A K 0 0 2) a nti b o d y ( A D A) 
 C o nc o mita nt me dicati o n  
6.  
St atistic al Met h o ds 
6. 1  
Ge ner al Met h o d ol o g y  
All  statistical  a nal y ses  will  be  c o n d ucte d  usi n g  S A S  v 9. 4  or  later  versi o n  o n  t he  Micr os oft 
Wi n d o ws O perati n g S yste m.  
All C R F data (ra w data) will be c o n verte d i nt o S D T M ( St u d y Data  Ta b ulati o n M o del) datasets, 
w hic h will be use d t o create A Da M ( A nal ysis Data M o del) data se ts. T he creati o n of t he S D T M 
a n d A Da M data sets will f oll o w t he C DI S C ( Cli nical Data I nterc h a n ge Sta n dar ds C o ns orti u m) 
sta n dar ds  a n d  t he  F D A  St u d y  Data  Tec hi nical  C o nf or ma nce  G ui de. All  a nal ysis  ta bles  a n d 
listi n gs will be create d fr o m t he A Da M data sets. 
C o nti n u o us  data  will  be  s u m marize d  usi n g  n  ( n u m ber  of  s u bjects wit h  n o n- missi n g 
o bser vati o ns),  mea n,  me dia n,  sta n dar d  de viati o n  ( S D),  mi ni m u m  v al ue,  a n d  ma xi m u m  val ue. 
Cate g orical data will be s u m marize d usi n g t he fre q ue nc y c o u nt a n d perce nta ge ( n, %) of s u bjects 
i n  eac h  cate g or y.  N u m ber  of  s u bjects  wit h  n o n- missi n g  val ues  or  n u m ber  of  s u bjects  wit h 
missi n g  val ues  (e. g.,  N ot  D o ne)  will  be  prese nte d,  w here  a p pr o p riate.  S u bjects  wit h  missi n g 
val ues  will  n ot  c o ntri b ute  t o  t he   de n o mi nat or  f or  perce nta ge  calc ulati o ns,  u nless  s pecifie d 
ot her wise. C o u nts of zer o i n a n y cate g or y will be prese nte d wit h o ut perce nta ge. All s u m maries 
will  be  prese nte d  f or  i n di vi d ual  treat me nt  gr o u ps.  I n  a d diti o n,  f or  s u m mar y  of  dis p ositi o n  a n d 
s u bject  baseli ne  c haracteristics,  t he  prese ntati o n  will  i ncl u de  all  3  gr o u ps  c o m bi ne d.  F or 
s u m mar y of efficac y a n d safet y e n d p oi nts, t he prese ntati o n will i ncl u de b ot h acti ve d ose gr o u ps 
c o m bi ne d. 
T he precisi o n r ules f or t he pres e ntati o n of s u m mar y statistics will be: 
 Sa m ple size ( n, N) a n d n u m ber of missi n g res p o nses (if dis pla ye d) – I nte ger 
 Mea n, c o nfi de nce i nter val, a n d me dia n – O ne m ore deci mal place t ha n re p orte d/c ollecte d 
 Sta n dar d de viati o n – T w o m ore d eci mal places t ha n re p orte d/c oll ecte d 
 Perce ntiles, mi ni m u m, ma xi m u m  – Sa me n u m ber of deci mal places as re p orte d/c ollecte d 
 Rati o – t w o deci mal places 
 Perce nta ge – o ne deci mal place ge nerall y, or t w o deci mal places  f or < 0. 1 % 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 2 of 3 5  
C o nfi de nti al  
T he data s u m maries will be acc o m pa nie d b y i n di vi d ual s u bject da ta listi n gs. All data a vaila ble 
fr o m  q uesti o n naires, e C R F,  a n d  e xter nal tra nsfer  (la bs)  will  be  liste d  a n d  will  i ncl u de  rele va nt 
s u bject i nf or mati o n, e. g., treat me nt gr o u p a n d st u d y da y. T he listi n gs will be s orte d i n t he or der 
of s u bject I D, a n d assess me nt date/ti me a n d assess me nt na me.  
F or eac h s u m mar y ta ble, a s u p p orti n g listi n g will be i de ntifie d  i n t he f o ot n ote.  
Dates  will  be  prese nte d  i n  t he  I S O- 8 6 0 1  f or mat  Y Y Y Y- M M- D D.  Ti me s  will  be  dis pla ye d  i n 
2 4- h o ur cl oc k f or mat. N u m beri n g f or ta bles, fi g ures a n d listi n gs will f oll o w I C H E 3 G ui deli ne 
(I C H, 1 9 9 6). 
Alter nati ve  met h o ds  of  a nal ysis  of  t he  data  ma y  be  c o nsi dere d  p ri or  t o  data base  l oc k  s h o ul d 
s o me  of  t he  ass u m pti o ns  u n derl yi n g  t he  pr o p ose d  a nal yses  n ot  be  met.  Reas o n  f or  de part ure 
fr o m t he pla n ne d met h o ds will be d oc u me nte d as a n a me n d me nt t o t he S A P or i n t he C S R. 
6. 2  
Visit Wi n d o w a n d U nsc he d ule d Assess me nts 
T here is n o visit wi n d o w f or t he b y- visit a nal ysis. Data will b e a nal yze d acc or di n g t o t he visit 
t he y are ass ociate d wit h, u nless s pecifie d ot her wise. 
6. 3  
A dj ust me nt f or C o v ari ates 
Baseli ne  a n d  ra n d o mizati o n  strat u m  ma y  be  a dj uste d,  w here  a p pr o priate,  i n  esti mati n g  t he 
bet wee n gr o u p differe nce usi n g A N C O V A, M M R M, or C oc hra n- Ma ntel- Hae nszel tests.  
6. 4  
H a n dli n g of Dr o p o uts, Missi n g D at a, a n d D at a Discre p a ncies 
F or t he e x pl orat or y e n d p oi nts of perce nt c ha n ge i n t he wee kl y 
, w he n ≥3 of 7 
dail y sc ores are a vaila ble, t he wee kl y a vera ge sc ore will be ca lc ulate d usi n g t he a vaila ble dail y 
sc ores.  T his  calc ulati o n i m plies  t he  missi n g  dail y  sc ores  are  the  sa me  as  t he  mea n  of  t he  n o n-
missi n g dail y sc ores. W he n > 4 dail y sc ores are missi n g, t he wee kl y sc ore will be set t o missi n g. 
F or t he wee kl y  
, w he n ≥4 of 8 wee kl y  
 sc ores are a vai la ble,  
 will be calc ulate d 
usi n g t he a vaila ble wee kl y  
 sc ores. Ot her wise, t he wee kl y  
 will be set t o missi n g. 
F or  t he 
,  Secti o n  6. 9),  w he n  ≥2 wee kl y  
 sc ores are 
a vaila ble,  
  will  be  calc ulate d  usi n g  t he  a vaila ble  wee kl y  
  sc ores.  Ot her wise,  
 
will be set t o missi n g. 
T he  e x pl orat or y  a nal ysis  f or  t he 
  will  be  base d  o n  t he 
 m o del ( Secti o n 6. 9). E xce pt f or t he i m plicit i m p utati o n descri be d a b o ve, n o i m p utati o n 
will  be  a p plie d  t o  t he  missi n g  data.  U n der  t he  M A R  ass u m pti o n, t he  
  a nal ysis  is 
c o nsi dere d u n biase d.  


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 3 of 3 5  
C o nfi de nti al  
A Es wit h i nc o m plete start or st o p dates (i.e., eit her da y or m o nt h is missi n g) will be c o nsi dere d 
treat me nt-e mer ge nt ( T E A E) u nless t he partial start date or t he st o p date c o nfir ms t he A E starte d 
or e n de d pri or t o St u d y Da y 1 (e. g., t he da y of t he A E start da te is u n k n o w n b ut t he m o nt h a n d 
year  i n dicate  t hat  t he  A E  starts   pri or  t o  St u d y  Da y  1).  A Es  with  missi n g  relati o ns hi p  t o  st u d y 
dr u g  will  be  i ncl u de d  i n  t he  “ Relate d”  cate g or y  f or  t he  s u m mar y  ta bles. A Es wit h missi n g 
se verit y will n ot be i ncl u de d i n the b y-se verit y s u m mar y ta ble b ut will be f o ot n ote d i n t he ta ble. 
W he n  t here  is  i nc o m plete  i nf or mati o n  re gar di n g  d osi n g  dates  f or   pri or  a n d  c o nc o mita nt 
me dicati o n, t he me dicati o n will be c o nsi dere d as a c o nc o mita nt me dicati o n u nless it c o ntra dicts 
wit h t he st o p date. F or e xa m ple,  a me dicati o n will be c o nsi dered a pri or me dicati o n if t he m o nt h 
a n d year of t he e n d date i n dicates a date bef ore St u d y Da y 1 e v e n t h o u g h t he start date c o ul d be 
missi n g.  
6. 5  
I nteri m A n al ysis 
N o i nteri m a nal ysis is pla n ne d.  
6. 6  
Ti mi n g of Fi n al A n al yses 
Data a nal ysis will c o m me nce after all s u bjects ha ve c o m plete d t he st u d y a n d t he st u d y data base 
is clea ne d a n d l oc ke d f or t he data pri or t o t he e xte n de d f oll o w- u p. N ote t he P K a n d A D A data 
ma y be l oc ke d se paratel y. 
6. 7  
M ultice nter St u d y 
T his  is  a  m ultice nter  st u d y.  Beca use  of  s mall  sa m ple  sizes  f or m ost  of  t he  sites,  n o  b y  site 
a nal ysis will be perf or me d. All sites will be p o ole d f or data a nal ysis a n d s u m mar y.  
6. 8  
M ulti ple C o m p aris o ns/ M ulti plicit y A dj ust me nt 
T o  c o ntr ol  f or  t he  fa mil y- wise  t y pe-I  err or  rate,  t he  f oll o wi n g  testi n g  pr oce d ures  will  be 
i m ple me nte d: 
1.  Test  t he  hi g h/l o w  d ose  ( Treat me nt  Gr o u ps  1  a n d  2)  c o m bi ne d  gr o u p  a gai nst  place b o 
( Treat me nt Gr o u p 3) f or t he pri mar y efficac y e n d p oi nt.  If p ≤0.0 5 t he n pr ocee d t o 
2.  Test  t he  hi g h/l o w  d ose  c o m bi ne d  gr o u p  a gai nst  place b o  f or  t he  1 st  sec o n dar y  efficac y 
e n d p oi nt.  If If p ≤0. 0 5 t he n pr ocee d t o 
3.  Test  t he  hi g h/l o w  d ose  c o m bi ne d  gr o u p  a gai nst  place b o  f or  t he  2 n d  sec o n dar y  efficac y 
e n d p oi nt.  If If p ≤0. 0 5 t he n pr ocee d t o 
4.  Test  t he  hi g h  d ose  a gai nst  place b o  f or  t he  pri mar y  efficac y  e n d p oi nt.    If  p ≤0. 0 5  t he n 
pr ocee d t o 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 4 of 3 5  
C o nfi de nti al  
5.  Test  t he  l o w  d ose  a gai nst  place b o  f or  t he  pri mar y  efficac y  e n d p oi nt.    If  p ≤0. 0 5  t he n 
pr ocee d t o 
6.  Re peat  a b o ve  Ste ps  4- 5  f or  testi n g  t he  1 st  sec o n dar y  efficac y  e n d p oi nt,  t he n  t he  2n d 
sec o n dar y efficac y e n d p oi nt.   
I n  t he  a b o ve  se q ue ntial  testi n g,  if  a n y  ste p  has  p > 0. 0 5  t he n  t he  tests  of  t his  ste p  a n d  of  all 
s u bse q ue ntial ste ps will be co nsi dere d n ot statisticall y si g nif ica nt. 
6. 9  
E x a mi n ati o n of S u b gr o u ps 
Ke y  e n d p oi nts  ma y  be  s u m marize d  b y  s u b gr o u p  t o  e x pl ore  t he  hete r o ge neit y  of  t he  treat me nt 
effect acr oss s u b gr o u ps. S u b gr o u ps t o be c o nsi dere d are: 
 Ra n d o mizati o n strat u m ( baseli ne hi g hest wee kl y P R O a vera ge sc or e 3 – 4. 9, 5. 0 – 1 0. 0) 
 S u bjects wit h E G or E G E al o ne, E G + E G E, s u bjects wit h E o E  
 Ge n der ( Male, Fe male) 
 A ge ( < 4 5, 4 5 t o < 6 5, 6 5 +) 
 Baseli ne peri p heral e osi n o p hil c o u nts ( < me dia n vs ≥me dia n) 
7.  
St atistic al A n al ysis 
7. 1  
A n al ysis P o p ul ati o ns 
T he p o p ulati o n of “all e nr olle d s u bjects” c o m prises all t h ose w h o si g ne d i nf or me d c o nse nt, met 
all eli gi bilit y criteria at Scree ni n g, a n d are ra n d o mize d t o o n e of t he treat me nt gr o u ps. 
7. 1. 1  S afet y P o p ul ati o n 
T he safet y p o p ulati o n c o m prises all s u bjects w h o ha ve si g ne d i n f or me d c o nse nt a n d recei ve d at 
least o ne d ose of st u d y dr u g. All safet y e n d p oi nts will be a nalyze d usi n g t his p o p ulati o n.  
7. 1. 2  Per Pr ot oc ol A n al ysis ( P P) p o p ul ati o n 
T he per pr ot oc ol p o p ul ati o n will i ncl u de all ra n d o mize d s u bject s w h o d o n ot ha ve maj or pr ot oc ol 
de viati o ns  a d versel y  affecti n g  t he  data  i nter pretati o n.    S o me  e xa m ples  of  P P  e xcl usi o n  criteria 
are 
 Di d n ot recei ve at least 2  d oses of st u d y me dicati o n 
 C ha n ge d d ose of s yste mic ster oi ds  a n d/ or starte d s yste mic ster oi d treat me nt d uri n g t he 
st u d y or i njecti o ns of ster oi ds i n t he st o mac h a n d/ or d u o de n u m (t his d oes n ot i ncl u de 
ster oi ds use d as pre me dicati o n t he da y bef ore a n d/ or t he da y of  st u d y dr u g i nf usi o ns).  
 Recei ve d ot her pr o hi bite d me dicat i o ns (e g, I L- 5 i n hi bit ors, d u pil u ma b) p ote ntiall y 
i m pacti n g efficac y d uri n g st u d y treat me nt 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 5 of 3 5  
C o nfi de nti al  
 Di d n ot ha ve at least 6 P R Os o ve r 1 4 da y peri o d at a n y ti me p oi nt after a d mi nistrati o n of 
sec o n d d ose. 
T he  st u d y  statisticia n  al o n g  wit h  t he  st u d y  tea m  will  re vie w  pr ot oc ol  de viati o ns  t o  i de ntif y 
s u bjects t o be e xcl u de d fr o m t he per pr ot oc ol a nal ysis p o p ulatio n.  T he P P e xcl usi o n criteria will 
be u p date d pri or t o t he data base l oc k a n d u n bli n di n g. T he P P p o p ulati o n will be s pecifie d pri or 
t o u n bli n di n g usi n g sai d e xcl usi o n criteria. 
7. 2  
Dis p ositi o n of S u bjects 
S u bject  de m o gra p hics  a n d  reas o ns  f or  scree ni n g  fail ure  will  be s u m marize d  f or  scree n-faile d 
s u bjects. 
S u bjects ( n a n d %) w h o c o m plete d or disc o nti n ue d fr o m t he st u d y  will be ta b ulate d b y treat me nt 
gr o u p  a n d  f or  all  3  gr o u ps  c o m bi ne d.  T he  pri mar y  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  ta b ulati o n.  T he  pri mar y  reas o ns  ma y  i ncl u de,  b ut  n ot  li mite d  t o,  a n y  of  t he 
f oll o wi n g: 
 S u bject wit h dre w c o nse nt 
 L ost t o f oll o w- u p 
 A d mi nistrati ve reas o n 
 A d verse e ve nt  
 I n vesti gat or decisi o n 
 Fail ure t o f oll o w re q u ire d st u d y pr oce d ures 
 Ot her 
S u bject  dis p ositi o n  will  be  s u m marize d  f or  all  e nr olle d  s u bject s.  S u bject  c o u nts  f or  t he  Safet y 
a n d  P P  p o p ulati o ns  will  be  i ncl u de d  i n  t he  ta ble.  A  data  listi n g  f or  s u bject  dis p ositi o n  will  be 
prese nte d f or all e nr olle d s u bjects.  
7. 3  
Pr ot oc ol De vi ati o ns 
Pr ot oc ol de viati o ns will i ncl u de, b ut are n ot li mite d t o 
 N o n-c o m plia nce wit h a n y sc he d ule d st u d y visit  
 N o n-c o m plia nce wit h st u d y treat me nt  
 Recei ve d pr o hi bite d me dicati o ns  (see Pr ot oc ol Secti o n 8. 1) 
 N o n-c o m plia nce wit h st u d y i ncl u si o n or e xcl usi o n criteria  
 N o n-c o m plia nce wit h st u d y assess me nt pr oce d ures  
S u bjects wit h maj or pr ot oc ol de viati o ns will be liste d. T he lis ti n g will i ncl u de a brief descri pti o n 
of t he de viati o n, de viati o n cate g or y, a n d if a p plica ble, st u d y da y w he n de viati o n occ urre d al o n g 
wit h ot her perti ne nt i nf or mati o n. 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 6 of 3 5  
C o nfi de nti al  
If  warra nte d  b y  t he  sa m ple  size,  s u bjects  ( n  a n d  %)  wit h  maj or  pr ot oc ol  de viati o ns  will  be 
ta b ulate d b y treat me nt gro u p a n d b y de viati o n cate g or y. 
S u bjects ( n a n d %) will be ta b ul ate d b y treat me nt gr o u p f or eac h a nal ysis p o p ulati o n. S u bjects 
w h o are e xcl u de d fr o m t he P P p o p ul ati o n will be liste d wit h rea s o ns f or e xcl usi o n.  
7. 4  
De m o gr a p hics a n d B aseli ne S u bject C h ar acteristics 
Descri pti ve  statistics  f or  s u bjec t  c haracteristics  a n d  baseli ne  val ues  will  be  prese nte d  f or  all 
p o p ulati o ns  b y  treat me nt  gr o u p  a n d  f or  all  3  gr o u ps  c o m bi ne d.  C o nti n u o us  varia bles  will  be 
s u m marize d wit h n, mea n, S D, a n d me dia n. Cate g orical varia bles will be s u m marize d wit h n a n d 
% of s u bjects f or eac h cate g or y, f or t he Safet y a n d P P p o p ulati o ns. 
7. 5  
B aseli ne Dise ase C h ar acteristics 
Baseli ne disease c haracteristics will be i ncl u de d i n t he s u bjec t data listi n g.  
7. 6  
Me dic al Hist or y 
S u bject i nci de nce ( n a n d %) of me dical hist or y (a n d c urre nt me d ical c o n diti o n bef ore si g ni n g t he 
i nf or me d c o nse nt) will be ta b ulate d b y Me d D R A S yste m Or ga n Class ( S O C) a n d Preferre d Ter m 
( P T). 
7. 7  
E C G 
A listi n g of E C G o verall i nter pr etati o n at scree ni n g visit will  be pr o vi de d. 
7. 8  
Pre g n a nc y Test 
A listi n g of pre g na nc y test res ults will be pr o vi de d. 
7. 9  
Tre at me nts 
7. 9. 1  Tre at me nt C o m pli a nce a n d E xte nt of E x p os ure 
S u m maries  of  treat me nt  c o m plia nc e  a n d  e x p os ure  t o  A K 0 0 2  will  be   base d  o n  t he  safet y 
p o p ulati o n. 
D urati o n of treat me nt e x p os ure is defi ne d as t he t otal n u m ber o f da ys a s u bject is e x p ose d t o t he 
st u d y  treat me nt.  T his  will  be  calc ulate d  f or  eac h  s u bject  b y  taki n g  t he  differe nce  bet wee n  t he 
date  of  t he  last  d ose  mi n us  t he  date  of  t he  first  d ose,  pl us  1 ( date  of  last  d ose  –  date  of  first 
d ose + 1). 
D urati o n  of  e x p os ure  will  be  s u m marize d  usi n g  descri pti ve  stati stics  ( n,  mea n,  sta n dar d 
de viati o n, me dia n, mi ni m u m, a n d ma xi m u m).  


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 7 of 3 5  
C o nfi de nti al  
Treat me nt c o m plia nce is defi ne d as t he n u m ber of i nf usi o ns s u bj ects recei ve d di vi de d b y 4 (i.e., 
t otal  n u m ber  of  i nf usi o ns  e x pecte d) ×   1 0 0 %.  Treat me nt  c o m plia nce  will  be  s u m marize d 
descri pti vel y.  I n  a d diti o n,  a n  o ve rall  c o m plia nce  t hat  i ncl u des  a d here nce  t o  treat me nt 
a d mi nistrati o n sc he d ule a n d a n y i nt err u pti o ns will be i ncl u de d i n t he data listi n g. 
T he  treat me nt  i nf usi o n  i nf or mati o n  (le n gt h,  v ol u me,  rate,  a n d  i nterr u pti o n)  will  be  i ncl u de d  i n 
t he s u bject data listi n g.  
7. 9. 2  Pri or a n d C o nc o mit a nt Me dic ati o ns  
Pri or  me dicati o ns  a n d  c o nc o mita nt  me dicati o ns  will  be  e xtracte d   fr o m  t he  Pri or/ C o nc o mita nt 
Me dicati o n C R F. Me dicati o ns ta ke n pri or t o St u d y Da y 1 will be c o nsi dere d as pri or me dicati o ns 
a n d me dicati o ns ta ke n o n or after St u d y Da y 1 will be c o nsi dere d as c o nc o mita nt me dicati o ns. 
Pri or a n d c o nc o mita nt me dicati o ns will be c o de d usi n g W H O Dr u g Dicti o nar y ( W H O D D Marc h 
2 0 1 8  release)  f or  Preferre d  Ter m  ( P T)  a n d  A nat o mical  T hera pe uti c  C he mistr y  ( A T C) 
classificati o n.  
Pri or a n d c o nc o mita nt me dicati o ns will be ta b ulate d se paratel y base d o n t he Safet y P o p ulati o n. 
T he n u m ber ( n a n d %) of s u bjects ta ki n g at least o ne me dicati o n  a n d t he n u m ber ( %) of s u bjects 
ta ki n g eac h me dicati o n at t he preferre d ter m le vel will be ta b ulate d b y A T C 4, a n d P T. S u bjects 
ta ki n g t he sa me P T me di cati o n t wice will o nl y be c o u nte d o nce. 
A  s u bject  data  listi n g  will  be  pr o vi de d  t o  i ncl u de  t he  re p orte d   me dicati o n  na me,  t he  W H O D D 
P T, A T C 4, st u d y da y a n d perti n e nt s u bject i nf or mati o n. 
A se parate data listi n g will i ncl u de s u bjects w h o ha ve recei ve d  pr o hi bite d me dicati o ns. 
7. 1 0  
A n al ysis of Pri m ar y Effic ac y E n d p oi nt 
7. 1 0. 1  Pri m ar y A n al ysis of Pri m ar y Effic ac y E n d p oi nt 
T he pri mar y efficac y e n d p oi nt is t he perce nt c ha n ge fr o m baseli ne t o Da y 9 9 i n t he n u m ber of 
e osi n o p hils per H P F i n gastric o r d u o de nal m uc osa wit h bi o ps y. F or s u bjects w h o pr o vi de gastric 
or  d u o de nal  o nl y  bi o ps y,  t he  calc ulati o n  will  be  base d  o n  t he  a vera ge  c o u nt  of  t he  hi g hest 
rea di n gs  fr o m  t he  res pecti ve  m uc osa  at  baseli ne  a n d  Da y  9 9.  F or  s u bjects  w h o  pr o vi de  b ot h 
gastric a n d d u o de nal bi o psies, t he calc ulati o n will be base d o n  t he a vera ge c o u nt of t he hi g hest 
rea di n gs fr o m t he Da y 9 9 bi o ps y t hat c orres p o n d i n l ocati o n ( gastric or d u o de nal) t o t he l ocati o n 
wit h  t he  hi g hest  a vera ge  c o u nt   at  baseli ne.    T his  e n d p oi nt  will  be  s u m marize d  b y  treat me nt 
gr o u p.  


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 8 of 3 5  
C o nfi de nti al  
T he  p o ole d  hi g h/l o w  d ose  gr o u p  a n d  eac h  acti ve  d ose  gr o u p  will be  c o m pare d  t o  t he  place b o 
gr o u p  i n  pair wise  c o m paris o n  usi n g  a nal ysis  of  c o varia nce  ( A N C O V A)  m o del  wit h  perce nt 
c ha n ge  fr o m  baseli ne  as  o utc o me,  treat me nt  as  fact or,  a n d  basel i ne  val ue  a n d  ra n d o mizati o n 
strat u m  as  c o variates.  T o  c o ntr ol  f or  t he  t y pe-I  err or,  t he  Gate kee pi n g  pr oce d ure  defi ne d  i n 
Secti o n 6. 8 will be f oll o we d.  
7. 1 0. 2  Sec o n d ar y A n al ysis of Pri m ar y Effic ac y E n d p oi nt 
I n t his a nal ysis, perce nt c ha n ge fr o m baseli ne will be a nal yze d b y t he C oc hra n- Ma ntel- Hae nszel 
χ 2 (c hi-s q uare)  test  f or  t he  r o w  mea n  sc ore  differe nce  stratifie d b y  t he  ra n d o mizati o n 
stratificati o n varia ble. A sa m ple S A S c o de f or t he pair wise c o m paris o n is as f oll o ws. 
 
P R O C  F R E Q  ; 
 
W H E R E   T R T P I N (‘ G R P 1’,’ P B O’) ; 
 
T A BL E S   R A N D S T R A * T R T P * P C H G / C M H  S C O R E = M O D RI DI T  RI S K DI F F( CL = N E W C O M B E)  ; 
 
O D S  O U T P U T   C M H = C M H P V AL(W H E R E =( AL T H Y P O T H E SI S = ' R o w  M e a n  Sc or es  Diff er')) ; 
R U N  ; 
 
7. 1 0. 3  Se nsiti vit y A n al yses of P ri m ar y Effic ac y E n d p oi nt 
Se nsiti vit y A nal ysis 
I n  t his  a nal ysis,  a  res p o n der  is  defi ne d  as  a n  e osi n o p hil  c o u nt  < 3 0  cells/ H P F.  S u bjects  wit h 
missi n g e osi n o p hil c o u nt will be c o nsi dere d n o n-res p o n ders.  A l o gistic re gressi o n  m o del wit h 
effects of treat me nt gr o u p, ra n d o mizati o n strat u m, a n d baseli ne  e osi n o p hil c o u nt will be use d t o 
a nal yze  t he  bet wee n  gr o u p  differe nce.  O d ds  rati o  a n d  t he  ass oci ate d  9 5 %  c o nfi de nce  i nter vals 
are  c o m p ute d  f or  t he  c o m paris o n  of  o d ds  of  ac hie vi n g  res p o nse  i n  t he  acti ve  treat me nt  gr o u p 
a gai nst t he o d ds i n t he pl ace b o gr o u p.  A sa m ple S A S c o de: 
 
P R O C  L O GI S TI C ; 
  CL A S S   gr o u p str at u m / P A R A M = gl m ; 
  M O D EL  r es p(R E F = ' 0') = gr o u p str at u m  b as e ; 
  E S TI M A T E  ' Gr p  1 ‐  Gr p  3'  gr o u p 1  0  ‐1  ; 
  E S TI M A T E  ' Gr p  2 ‐  Gr p  3'  gr o u p 0  1  ‐1  ; 
  E S TI M A T E  ' A v g  Gr p 1, 2 ‐  Gr p  3'  gr o u p 0. 5  0. 5  ‐1  ; 
  O D S  O U T P U T   E S TI M A T E S = p ar m est ; 
R U N  ; 
I n a d diti o n t o t he res p o n der a nalysis, a c u m ulati ve distri b uti o n f u ncti o n ( C D F) will be pl otte d f or 
t he 3 treat me nt gr o u ps, w here t he h oriz o ntal a xis is t he c ha n ge fr o m baseli ne i n e osi n o p hil c o u nt 
( x), ra n gi n g fr o m t he s mallest ( ne gati ve val ue mea ni n g re d ucti on) t o t he lar gest ( p ositi ve val ue 
mea ni n g i ncrease) o bser ve d i n t he  trial, a n d t he vertical a xis is t he perce nta ge of patie nts w h ose 
e osi n o p hil c o u nt is ≤x cells/ H P F. 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 2 9 of 3 5  
C o nfi de nti al  
7. 1 1  
A n al ysis of Sec o n d ar y Effic ac y E n d p oi nts  
A c u m ulati ve distri b uti o n f u ncti o n ( C D F) pl ot will be ge nerate d  f or t he 3 treat me nt gr o u ps f or 
t he perce nt c ha n ges fr o m baseli ne i n t he T S S sc ores a vera ge d o ver t he 1 4 dail y sc ores starti n g 
wit h t he da y of t he last d ose t o t he da y bef ore t he e n d of t he st u d y bi o ps y.  ( See Secti o n 5. 2 f or 
detail of t he calc ulati o n.) 
7. 1 1. 1  Tre at me nt Res p o n der at E n d of St u d y Tre at me nt 
Pr o p orti o n  of  patie nts  wit h  a  > 3 0 %  re d ucti o n  i n  T S S  c o m bi ne d  wi t h  a  > 7 5 %  re d ucti o n  i n 
e osi n o p hils i n t he gastric a n d/ or d u o de nal m uc osa will be a nal y ze d usi n g t he l o gistic re gressi o n 
m o del si milar t o Secti o n 7. 1 0. 2 Se nsi vit y A nal ysis.  T he calc ul ati o n of t he T S S sc ore is f o u n d i n 
Secti o n 5. 2 1 st Sec o n dar y E n d p oi nt.   
As  a n  e x pl orat or y  a nal ysis,  t he  a nal ysis  of  t he  treat me nt  res p o n der  will  be  re peate d  f or  select 
s u b gr o u ps ( Secti o n 6. 9) s uc h as E G, E G E, a n d E G + E G E. F or eac h s u b gr o u p, se parate l o gistic 
re gressi o n a nal ysis will be perf or me d si milar t o t he se nsiti vity a nal ysis f or t he pri mar y e n d p oi nt 
of Secti o n 7. 1 0. 3. I n t he a nal ysis, t w o acti ve d ose gr o u ps will  be c o m bi ne d f or t he c o m paris o n t o 
t he place b o gr o u p. 
7. 1 1. 2  P atie nt Re p orte d O utc o me – T S S at E n d of St u d y Tre at me nt 
T he  a vera ge  of  T S S  sc ore  at  t he  e n d  of  st u d y  treat me nt  is  calc u late d as per t he 1st  Sec o n dar y 
E n d p oi nt ( Secti o n 5. 2).  A N C O V A will be a p plie d wit h treat me nt as fact or, a n d baseli ne val ue 
a n d  ra n d o mizati o n  strat u m  as  c o variates.    T he  or der  of  t he  a nal ysis  f oll o ws  t he  hierarc h y 
defi n de d i n Secti o n 6. 8.  
7. 1 2  
A n al ysis of E x pl or at or y E n d p oi nts 
 C ha n ge i n 
 will be a nal yze d usi n g  
 as descri be d 
bel o w. O nl y t he 
 c ollecte d pri or t o st u d y dr u g d osi n g will be i ncl u de d i n 
t he m o del. T he  
 m o del i ncl u des treat me nt, wee k, treat me nt- by- wee k i nteracti o n 
as fi xe d fact ors, a n d baseli ne as c o variates. S u bject will be t he re peate d meas ure fact or. 
T he  c o varia nce  matri x  f or  t he  re peate d  meas ure me nts  will  ta ke  t he f or m of T oe plitz 
( T O E P).  If  t he  c o m p utati o n  d oes  n ot  c o n ver ge,  it  will  be  re d uced  t o  t he  first  or der 
a ut ore gressi ve  [ A R( 1)]  f oll o we d  b y  c o m p o u n d  s y m metr y  ( C S).  T he wee kl y  c ha n ge 
sc ores fr o m Wee k 1 u p t o Wee k 1 4 will be i ncl u de d i n t he m o del.  
 C ha n ge  fr o m  baseli ne  i n  t he 
  sc ores  a verage d  o ver  t he  1 4  dail y 
sc ores  starti n g  wit h  t he  da y  of  t he  last  d ose  t o  t he  da y  bef ore  t he  e n d  of  st u d y  bi o ps y.  
( See 1st Sec o n dar y E n d p oi nt f or t he calc ulati o n of a vera ge.) F or patie nts w h ose bi o ps y is 
c ollecte d pri or t o Da y 9 9 d ue t o earl y disc o nti n uati o n, t he a ve ra ge of t he last 1 4 da ys of 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 3 0 of 3 5  
C o nfi de nti al  
sc ores rec or de d f or t hat patie nt will be use d f or t he a nal ysis  will be a nal yze d usi n g t he 
sa me met h o d as f or t he  
 a n d T S S sc ores. 
 T he  a vera ge  of  
  sc ores  at  t he  e n d  of  st u d y  treat me nt  is  calc ulate d  as  per  t he  1st 
Sec o n dar y E n d p oi nt  ( Secti o n  5. 2).   
  will  be  a p plie d  wit h treat me nt  as  fact or, 
a n d baseli ne val ue a n d ra n d o miza ti o n strat u m as c o variates.  
 Perce nt  C ha n ge  i n  t he  n u m ber  of 
  i n  patie nts  wit h 
  will  be  a nal yze d  usi n g  t he  sa me  met h o d  as  f or  the  pri mar y  efficac y 
e n d p oi nt (see Secti o n 7. 1 0. 1).  
 Pr o p orti o ns of E G, E G E, a n d E o E patie nts wit h a vera ge 
 per H P F ( E G a n d 
E G E)  or  
  per  H P F  ( E o E)  fr o m 
 will be 
a nal yze d  usi n g  t he  sa me  met h o d  as  t he  se nsiti vit y  a nal ysis  f or t he  pri mar y  efficac y 
e n d p oi nt (see Secti o n 7. 1 0. 3). 

 
 (res pecti vel y) will be s um marize d at baseli ne a n d 
Wee k 1 4 ( Da y 9 9). 
 C ha n ges  i n  t he  n u m ber  of  
  se paratel y  i n 
 
 ma y be a nal yze d usi n g  
 si milarl y t o t he pri mar y e n d p oi nt a nal ysis if 
sa m ple sizes all o w.  
 C ha n ge fr o m baseli ne i n t he sc ori n g of 
 
will be s u m marize d descri pti vel y usi n g mea n, S D, a n d me dia n.  I n di vi d ual assess me nts 
will be s u m marize d usi n g fre q ue nc y ta bles 
 C ha n ges fr o m baseli ne i n t he  
 d o mai n a n d s u m mar y sc ores wi ll be a nal yze d si milarl y 
t o t he P R O T S S sc ores. I nstea d of usi n g t he wee kl y sc ore, t he anal ysis will be base d o n 
t he  
 ite m sc ores c ollecte d at eac h visit. T he c o m p utati o n of t he d o mai n sc ores a n d 
s u m mar y sc ores will be pr o vi de d b y t he O pt u m P R O C o R E s oft ware. 
 C ha n ge fr o m baseli ne i n t he 
 f or E o E patie nts 
will be s u m marize d. 
 Perce nt  c ha n ges  fr o m  baseli ne  i n
  f or  a vera ges  of  Wee ks  1 3- 1 4,  1 1- 1 4,  a n d 
Wee ks 9- 1 4, a n d se paratel y f or eac h i n di vi d ual wee k will be s u m marize d.  Baseli ne f or 
eac h of t he s y m pt o m sc ores is defi ne d t he a vera ge of all sc ores  f or t hat s y m pt o m pri or t o 
t he first d ose of t he st u d y dr u g.  T he p ost baseli ne wee kl y 
 a n d t heir perce nt 
c ha n ges  will  be  s u m marize d  f or  eac h  treat me nt  gr o u p  e ver y wee k.  T he wee kl y perce nt 
c ha n ges  will  be  a nal yze d  usi n g  t he  
  m o del  as  descri be d  i n  t he  a nal ysis  f or  t he 
peri p heral  e osi n o p hil  c o u nts.  T he  c o m paris o n  bet wee n  t he  acti ve   d ose  a n d  place b o 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 3 1 of 3 5  
C o nfi de nti al  
gr o u ps f or a vera ges of Wee ks 1 3- 1 4, 1 1- 1 4, a n d 9- 1 4 will be bas e d o n t he a vera ges of t he 
least s q uares mea ns f or t he c orres p o n di n g wee ks usi n g si m ple c o ntrasts. T he c o m paris o n 
f or eac h i n di vi d ual wee k will be carrie d o ut si milarl y.  P- val ues a n d c o nfi de nce i nter vals 
will be prese nte d wit h o ut m ulti plicit y a dj ust me nt. 
 
P R O C  MI X E D  D A T A = X X X X ; 
 
C L A S S  T R T P U S U BJI D W E E K; 
 
M O D E L  P C H G = B A S E T R T P W E E K T R T P * W E E K / D D F M = K R ;  
 
R E P E A T E D  W E E K / S U BJ E C T = U S U BJI D( T R T P) T Y P E = T O E P ; 
 
E S TI M A T E  " G R P 1- G R P 3 @ W 9- 1 4 A v g" T R T P  6   0  -6  
  
  
T R T P * W E E K 0   0   0   0   0   0   0   0   1   1   1   1   1   1   
 
 
  
 
0   0   0   0   0   0   0   0   0   0   0   0   0   0   
 
 
  
 
0   0   0   0   0   0   0   0  -1  -1  -1  -1  -1  -1   
  
  
  
  
/ C L DI VI S O R =6 ; 
 
E S TI M A T E  " G R P 2- G R P 3 @ W 1 3- 1 4 A v g" T R T P   0  2  -2  
  
  
T R T P * W E E K 0   0   0   0   0   0   0   0   0   0   0   0   0   0   
 
 
  
 
0   0   0   0   0   0   0   0   0   0   0   0   1   1  
 
 
  
 
0   0   0   0   0   0   0   0   0   0   0   0  -1  -1   
  
  
  
  
/ C L DI VI S O R =2 ; 
 
E S TI M A T E  " G R P 1- G R P 3 @ W 1" T R T P  1  0  -1  
  
  
T R T P * W E E K   1   0   0   0   0   0   0   0   0   0   0   0   0   0   
 
 
 
 
 0   0   0   0   0   0   0   0   0   0   0   0   0   0   
 
 
 
 
-1   0   0   0   0   0   0   0   0   0   0   0   0   0   
 
 
 
 
/ C L ; 
R U N ; 
 
 C ha n ges fr o m baseli ne i n t he 
 f or a vera ges of Wee ks 1 3- 1 4, 1 1-
1 4 a n d Wee ks 9- 1 4 a n d se paratel y f or eac h i n di vi d ual wee k will be a nal yze d i n t he sa me 
wa y as f or t he perce nt c ha n ge fr o m baseli ne.  
 C ha n ge fr o m baseli ne i n 
 will be a nal yze d usi n g M M R M si milarl y as descri be d 
f or a n d  
 a n d T S S sc ores.  

  will  be  s u m marize d  at  baseli ne  a nd  Wee k  1 4  usi n g 
ge o metric mea n, c oefficie nt of  variati o n, me dia n, a n d mi ni m u m an d ma xi m u m. 
 S u bject c o u nts at eac h 
 at Da y 9 9 will be ta b ulate d. 
7. 1 3  
A n al ysis of P h ar m ac o ki netic E n d p oi nt 
Ser u m c o nce ntrati o ns of A K 0 0 2 will be s u m marize d f or eac h treat me nt gr o u p b y st u d y visit.  


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 3 2 of 3 5  
C o nfi de nti al  
7. 1 4  
S afet y A n al yses 
7. 1 4. 1  A d verse E ve nts 
Safet y assess me nts will be base d mai nl y o n t he nat ure, fre q ue nc y, relati o ns hi p, a n d se verit y of 
a d verse  e ve nts  ( A Es).  A Es  will  be  c o de d  b y  pri mar y  s yste m  or ga n  class  ( S O C)  a n d  preferre d 
ter m  ( P T)  acc or di n g  t o  t he  Me dical  Dicti o nar y  f or  Re g ulat or y  Acti vities  ( Me d D R A)  versi o n 
2 1. 0.  T he  treat me nt-e mer ge nt  a d verse  e ve nts  ( T E A Es)  will  be  s u m marize d  b y  t he  n u m ber  a n d 
perce nta ge ( n a n d %) of s u bjects i n eac h S O C a n d P T. F or s u m mar ies b y relati o ns hi p t o st u d y 
dr u g, “ p ossi bl y relate d” will be c o m bi ne d wit h “relate d”, a n d “ u nli kel y/re m otel y relate d” will be 
c o m bi ne d wit h “ n ot relate d.” W he n m ulti ple A Es are re p orte d wit h t he sa me P T, t he A E of t he 
str o n gest  relati o n  will  be  i nclu de d  i n  s u m mar y  b y  relati o ns hi p,   a n d  t he  A E  of  t he  m ost  se vere 
gra de will be i ncl u de d i n t he s u m mar y b y se verit y ta ble. 
T he f oll o wi n g A E i nci de nce ta bles will be prese nte d.  
 O ver vie w of T E A Es t o i ncl u de 
o  N u m ber ( %) of patie nts w h o re p orte d at least o ne T E A E  
o  N u m ber ( %) of patie nts w h o re p orte d at least o ne treat me nt-rela te d T E A E 
o  N u m ber ( %) of patie nts w h o re p or te d at least o ne se vere T E A E 
o  N u m ber ( %) of patie nts w h o re p orte d at least o ne seri o us T E A E  
o  N u m ber  ( %)  of  patie nts  w h o  re p orte d  at  least  o ne  T E A E  lea di n g  t o  treat me nt 
disc o nti n uati o n  
o  N u m ber ( %) of patie nts w h o die d o n st u d y 
 T E A Es  b y  P T  s orte d  b y  decreasi n g  or der  of  s u bject  i nci de nce  i n  t he  c o m bi ne d 
treat me nt gr o u p 
 T E A Es b y S O C a n d P T i n al p ha betical or der 
 T E A Es b y S O C, P T, a n d ma xi m u m se verit y 
 T E A Es b y S O C, P T, a n d str o n gest r elati o ns hi p t o st u d y dr u g  
 T E A Es lea di n g t o wit h dra wal b y S O C  a n d P T, if warra nte d b y sa m ple size 
 Seri o us T E A Es b y S O C a n d P T, if warra nte d b y sa m ple size 
All A Es will be liste d wit h o ns et/st o p da y, relati o ns hi p t o st u d y dr u g, se verit y, acti o n ta ke n, a n d 
o utc o me. Perti ne nt s u bject i nf or mati o n i ncl u di n g treat me nt gr o u p a n d de m o gra p hics will als o be 
i ncl u de d.  


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 3 3 of 3 5  
C o nfi de nti al  
Se parate listi n gs will be pr o vi de d f or T E A Es lea di n g t o st u d y d isc o nti n uati o n, T E A Es of s pecial 
i nterest, a n d Treat me nt-e mer ge nt seri o us A Es ( T E S A Es).  
7. 1 4. 2  L a b or at or y Test 
La b orat or y  data  will  be  s u m marize d  b y  prese nti n g  s u m mar y  statis tics  of  ra w  data  a n d  c ha n ge 
fr o m baseli ne val ues ( mea ns, me dia ns, sta n dar d de viati o ns, ra n ges). F or q ua ntitati ve la b orat or y 
para meters, b ot h act ual val ues a n d c ha n ge fr o m baseli ne val ues will be s u m marize d. 
S hift  ta bles  will  be  prese nte d,  i n  w hic h,  la b  test  res ults  at  baseli ne  a n d  p ost- baseli ne  will  be 
classifie d  i nt o  bel o w  ( < L L N),  wit hi n  ( ≥L L N  a n d  ≤U L N),  a n d  a b o ve   ( > U L N)  n or mal  ra n ges. 
S u bject  i nci de nces  ( n  a n d  %)  will be  prese nte d  f or  t he  s hift  fr o m  baseli ne t o  t he p ost- baseli ne 
visits. 
N ote  t he  s u m mar y  a n d  s hift  ta bles  will  o nl y  use  t he  pla n ne d/sc h e d ule d  tests.  H o we ver,  b ot h 
sc he d ule d a n d u nsc he d ule d/re peat tests will be i ncl u de d i n t he data listi n g. 
A  c o m plete  la b orat or y  data  lis ti n g,  i ncl u di n g  he mat ol o g y,  bi oc he mistr y,  uri nal ysis,  a n d  A nti-
Dr u g- A nti b o dies ( A D A) will be pr o vi de d f or all s u bjects.  
7. 1 4. 3  Vit al Si g ns, Hei g ht a n d Wei g ht, a n d Ot her S afet y Me as ures 
Vital  si g ns  will  be  s u m marize d  b y  prese nti n g  s u m mar y  statistics   of  ra w  data  a n d  c ha n ge  fr o m 
baseli ne val ues ( mea ns, me dia ns, sta n dar d de viati o ns, ra n ges) f or eac h sc he d ule d visit a n d ti me 
p oi nt. A data listi n g will i ncl u de vital si g ns fr o m all visits.   
 
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 3 4 of 3 5  
C o nfi de nti al  
7. 1 4. 4  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 he s y m pt o m- directe d p h ysical e xa ms will be i ncl u de d i n t he b y-
s u bject data listi n g. 
7. 1 4. 5  A n al ysis of A nti- Dr u g A nti b o d y 
N u m ber  ( %)  of  s u bjects  w h o  are  A D A  p ositi ve  at  a n y  ti me  after  r ecei vi n g  st u d y  dr u g  a n d 
n u m ber ( %) of s u bjects w h o are A D A p ositi ve at t he e n d of st u d y  will be cr oss-ta b ulate d b y t heir 
A D A stat us at pre d ose.   
8.  
V ali d ati o n  
T he  Cli nical  O perati o ns  a n d  Data  Ma na ge me nt  at  Alla k os  will  w or k  wit h  E D C/ Data 
Ma na ge me nt  ( D M)  ve n d or  t o  e ns ure  t hat  t he  data  c ollecte d  f or  t h e  st u d y  are  of  t he  hi g hest 
q ualit y p ossi ble. T he st u d y m o nit or will be res p o nsi ble f or re v ie wi n g a n d verif yi n g t he acc urac y 
of t he data rec or de d o n t he electr o nic case re p ort f or ms (e C R Fs ) directl y fr o m s o urce d oc u me nts 
at  t he  i n vesti gati ve  site.  T he  D M  ve n d or  will  be  res p o nsi ble  f or  perf or mi n g  e dit  c hec ks  a n d 
re vie wi n g all data e ntere d i nt o t he electr o nic data base t o i de ntif y discre pa nt a n d/ or i nc o nsiste nt 
val ues a n d t o se n d q ueries t o t he cli nical sites. T he I n vesti gat or will be res p o nsi ble f or a ns weri n g 
q ueries a b o ut discre pa nt data a n d pr o vi di n g elect r o nic si g nat ures t o c o nfir m data i nte grit y.  
T he  pr o gra m mi n g  of  Ta bles,  Listi n gs  a n d  Fi g ures  ( T L Fs)  base d  o n  t he cli nical data is 
o uts o urce d. Alla k os see ks t o e ns ur e t he q ualit y of t he re p orts pr o vi de d b y t he C R O i n t he f or m of 
T L Fs passi n g a ri g or o us vali d ati o n pr ocess as f oll o ws:  
 Deri ve d datasets will be i n de pe n de ntl y re pr o gra m me d b y a sec o n d  pr o gra m mer. T he 
se parate datasets pr o d uce d b y the 2 pr o gra m mers m ust matc h 1 0 0 % .  
 Ta bles will be i n de pe n de ntl y re pr o gra m me d b y a sec o n d pr o gra m mer a n d t he res ults 
fr o m b ot h pr o gra ms m ust matc h.  
 Fi g ures will be c hec ke d f or c o nsiste nc y a gai nst c orres p o n di n g t a bles a n d listi n gs, or 
i n de pe n de ntl y re pr o gra m me d if t here are n o c orres p o n di n g ta bles or listi n gs.  
 Listi n gs  will  be  c hec ke d  f or  c o nsiste nc y  a gai nst  c orres p o n di n g  ta bles,  fi g ures,  a n d 
deri ve d datasets.  
All p ost h oc a nal ysis, if acce pte d f or i ncl usi o n i n t he st u d y r e p ort, will f oll o w t he sa me q ualit y 
pr ocess  as  state d  a b o ve.    T he  e ntire  set  of  T L Fs  will  be  c hec ke d  f or  c o m plete ness  a n d 
c o nsiste nc y pri or t o its  deli ver y t o Alla k os.  
 


Pr ot oc ol A K 0 0 2- 0 0 3 
Statistical A nal ysis Pla n ( Versi o n 2) 
Date: 2 9 Ma y 2 0 1 9 
Alla k os, I nc.  
Pa ge 3 5 of 3 5  
C o nfi de nti al  
9.  
Refere nces 
I nter nati o nal C o u ncil f or Har m o nisati o n (I C H). G ui deli ne f or i nd ustr y E 3, str uct ure a n d c o nte nt 
of cli nical st u d y re p orts, J ul y 1 9 9 6.