Conditions: Atopic Dermatitis
Keywords: AD Dermatitis Eczema
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 131
Healthy volunteers: no

Brief summary:
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous lirentelimab (AK002), given every 2 weeks for 7 doses, in adult subjects with moderate-to-severe AD inadequately controlled by topical treatments. Subjects who complete the randomized, double-blind, placebo-controlled treatment period may have the option to enroll in an open-label extension period and receive up to 7 doses of subcutaneous lirentelimab.

Detailed description:

Arms:
arm 1: Subjects in this arm will receive 7 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks. arm 2: Placebo

Interventions: intervention 1: AK002 intervention 2: Placebo
Intervention descriptions: intervention 1: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1)monoclonal antibody directed against Siglec-8 intervention 2: Placebo

Protocol document:
Prot_000.pdf: 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and 
Safety of Subcutaneous Lirentelimab in Adult Subjects with Moderate-to-Severe Atopic 
Dermatitis Inadequately Controlled by Topical Treatments 
NCT Number: NCT05155085 
Document Date: 08 September 2023 
IRB Approval Date: 12 September 2023 






Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 3 of 1 3 5 
C o nfi d e 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 rea d t h e pr ot oc ol s pecifie d bel o w. I n m y f or mal ca p acit y as Pri nci pal I n v esti g at 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 s u bjects 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 m el y i nf or mati o n, as o utli ne d i n t he pr ot o c 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 uire 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 gree t o mai ntai n t he pr oce d ures re q uir e 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, t he Declarati o n of H elsi n ki 
i n t h e a p plica ble versi o n, a n d t h e a p plica bl e le gal a n d re g ulat or y re q uir e me nts, as well as 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 b er:
A K 0 0 2- 0 1 8 
I N D N u m ber: 
1 5 7 5 6 6 
N C T N u m ber:   
N C T 0 5 1 5 5 0 8 5
E u d r a C T N u m ber:   
2 0 2 2- 0 0 1 6 2 5- 7 9 
Pr ot oc ol Title:  
A P h ase 2 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 u ate t he Efficac y a n d Safet y of S u bc uta ne o us 
Lire nteli ma b i n A d ult S u bjects wit h M o derate-t o- Se vere At o pic 
Der m atitis I n a de q u atel y C o ntr olle d b y T o pical Treat m e nts 
Pr ot oc ol A me n d m e nt 6:  
0 8 Se pte m ber 2 0 2 3 
 
 
 
I n v esti g at or Pri nte d N a me: 
 
 
I n v esti g at or Si g n at ure:
D ate: 
 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 4 of 1 3 5 
C o nfi d e nti al  
Ta bl e of C o nt e nts 
Cli ni c al Res e arc h Pr ot o c ol A K 0 0 2- 0 1 8 ........................................................................................ 1
I n v esti g at or Pr ot oc ol A gree me nt.................................................................................................. 3
T a bl e of C o nte nts ........................................................................................................................... 4
List of Ta bles ......................................................................................................................... 1 1
List of Fi g ure ......................................................................................................................... 1 1
List of A b bre vi ati o ns ............................................................................................................. 1 2
1.
Pr ot oc ol S y n o psis ................................................................................................................. 1 6
2.
B a c k g r o u n d .......................................................................................................................... 3 1
2. 1  
Si glec- 8 a n d Lire nteli ma b ........................................................................................... 3 1
2. 2  
O ver vie w of N o ncli nical St u dies ................................................................................ 3 1
2. 3  
O ver vie w of Cli nical St u dies ...................................................................................... 3 3
2. 4  
At o pic Der matitis a n d Rati o nale f or t he St u d y ........................................................... 3 4
3.
R ati o n ale f or D os e Sel ecti o n ............................................................................................... 3 6
4.
St u d y O bjecti v es a n d E n d p oi nts ........................................................................................ 3 7
4. 1  
Pri mar y O bjecti ve a n d E n d p oi nt ................................................................................ 3 7
4. 2
Sec o n dar y O bj ecti v es a n d E n d p oi nts ......................................................................... 3 7
4. 3
E x pl orat or y O bjecti v es a n d E n d p oi nts ....................................................................... 3 7
4. 4  
Safet y O bjecti ves ........................................................................................................ 3 8
5.
St u d y Desi g n ......................................................................................................................... 3 9
5. 1  
St u d y O ver vie w .......................................................................................................... 3 9
5. 2  
Sc he d ule of E ve nts a n d St u d y Dia gra m ..................................................................... 4 1
6.
Esti m a n d C o nsi der ati o ns .................................................................................................... 4 7
7.
Criteri a f or E v al u ati o n ........................................................................................................ 4 8
7. 1  
Safet y E n d p oi nts ......................................................................................................... 4 8


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 of 1 3 5 
C o nfi d e nti al  
7. 2
P h ar mac o ki netic E n d p oi nts ........................................................................................ 4 8
7. 2. 1 
Pri mar y Efficac y E n d p oi nts ......................................................................... 4 8
7. 2. 2 
S ec o n dar y Efficac y E n d p oi nts ..................................................................... 4 9
7. 2. 3 
E x pl orat or y Effi cac y E n d p oi nts ................................................................... 4 9
8.
S u bject Selecti o n .................................................................................................................. 5 0
8. 1  
N u m ber of S u bjects .................................................................................................... 5 0
8. 2  
N u m ber of Sit es .......................................................................................................... 5 0
8. 3  
St u d y P o p ulati o n ......................................................................................................... 5 0
8. 4  
I n cl usi o n Criteria ........................................................................................................ 5 0
8. 5  
E xcl usi o n Criteria ....................................................................................................... 5 2
8. 6  
Safet y E val uati o ns ...................................................................................................... 5 4
9.
Pri or a n d C o nc urre nt Me dic ati o ns .................................................................................... 5 5
9. 1  
Pr o hi bit e d Me dicati o ns ............................................................................................... 5 6
9. 2  
All o we d Me dicati o ns .................................................................................................. 5 6
9. 3  
Resc ue Me dicati o ns .................................................................................................... 5 7
1 0.
St u d y Tre at me nt .................................................................................................................. 5 8
1 0. 1
F or m ulati o n of Test Pr o d uct a n d Place b o .................................................................. 5 8
1 0. 2
St u d y Dr u g Pac ka gi n g a n d La beli n g .......................................................................... 5 9
1 0. 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 ....................................................... 5 9
1 0. 4  St u d y Dr u g D ose a n d D osi n g Re gi me n ...................................................................... 5 9
1 0. 5  Pre parati o n of St u d y Dr u g .......................................................................................... 6 0
1 0. 6  St u d y Dr u g A d mi nistrati o n......................................................................................... 6 0
1 0. 7  St u d y Dr u g St ora g e ..................................................................................................... 6 0
1 0. 8  St u d y Dr u g Acc o u nta bilit y ......................................................................................... 6 1
1 1.
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 ................................. 6 1


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 of 1 3 5 
C o nfi d e nti al  
1 1. 1
S u bject N u m beri n g ..................................................................................................... 6 1
1 1. 2  Stratificati o n a n d Ra n d o mizati o n ............................................................................... 6 1
1 1. 3
Bli n di n g ...................................................................................................................... 6 2
1 1. 4  Brea ki n g t he Bli n d ...................................................................................................... 6 3
1 2.
St u d y Pr oce d u res a n d G ui deli nes ...................................................................................... 6 3
1 2. 1  P har mac o d y na mic/ Efficac y- Relate d Pr oce d ures ........................................................ 6 4
1 2. 1. 1
Vali date d I n vesti gat or Gl o bal Assess me nt................................................... 6 4
1 2. 1. 2
Ecze ma Area a n d Se v erit y I n d e x ................................................................. 6 4
1 2. 1. 3
 ............................................................ 6 5
1 2. 1. 4
 ..................................... 6 5
1 2. 1. 5
 ................................................................... 6 5
1 2. 1. 6
 .................................................................. 6 5
1 2. 1. 7
At o pic C o n diti o ns Q uesti o n naire ................................................................. 6 6
1 2. 1. 8
P h ot o gra p hs .................................................................................................. 6 6
1 2. 1. 9
C o m plete Bl o o d C o u nt wit h Differe ntial ..................................................... 6 6
1 2. 1. 1 0
Fres h bi o psies ............................................................................................... 6 7
1 2. 2  Safet y- Relate d Pr o ce d ures .......................................................................................... 6 7
1 2. 2. 1
C o nc o mita nt Me dicati o ns ............................................................................ 6 7
1 2. 2. 2
C o m plete P h ysical E xa mi n ati o n .................................................................. 6 7
1 2. 2. 3
B o d y Wei g ht a n d Hei g ht .............................................................................. 6 8
1 2. 2. 4
S y m pt o m- Directe d P h ysical E xa mi nati o n ................................................... 6 8
1 2. 2. 5
Electr ocar di o gra m ........................................................................................ 6 8
1 2. 2. 6
Pre vi o us A D Dia g n osis a n d Treat me nts Re vie w ......................................... 6 8
1 2. 2. 7
Vital Si g ns .................................................................................................... 6 9
1 2. 3  Cli nical La b orat or y Meas ure me nts............................................................................. 6 9
1 2. 3. 1
Bl o o d C he mistr y Pr ofile ............................................................................... 7 0
1 2. 3. 2
Pre g n a nc y T est a n d F olli cle- Sti m ulati n g H or m o ne ..................................... 7 1


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 of 1 3 5 
C o nfi d e nti al  
1 2. 3. 3
Effecti ve M et h o ds of C o ntrace pti o n f or Alla k os St u dies ............................ 7 1
1 2. 3. 4
Uri nal ysis ..................................................................................................... 7 3
1 2. 3. 5
Ser ol o g y ....................................................................................................... 7 3
1 2. 3. 6
A nti- Lire nteli ma b A nti b o dies ...................................................................... 7 3
1 2. 3. 7
Bl o o d f or P har mac o ki neti cs ......................................................................... 7 4
1 2. 3. 8
Bl o o d f or I g E ................................................................................................ 7 4
1 2. 3. 9
C O VI D- 1 9 Testi n g ....................................................................................... 7 4
1 3.
E v al u ati o ns a n d P r oce d ures b y Visit ................................................................................. 7 5
1 3. 1  Scree ni n g Da y ( ~ D a y - 1 4)/ Scree ni n g Peri o d ............................................................. 7 5
1 3. 2  Da y 1 – Ra n d o mizati o n/ D ose 1/ Baseli ne ................................................................... 7 6
1 3. 3  Da y 8 ( ± 3) ................................................................................................................... 7 7
1 3. 4  Da y 1 5 ( ± 5) – D os e 2 .................................................................................................. 7 8
1 3. 5  Da y 2 9 ( ± 5) – D os e 3 .................................................................................................. 7 8
1 3. 6  Da y 4 3 ( ± 5) – D os e 4 .................................................................................................. 7 9
1 3. 7  Da y 5 7 ( ± 5) – D os e 5 .................................................................................................. 8 0
1 3. 8  Da y 7 1 ( ± 5) – D os e 6 .................................................................................................. 8 1
1 3. 9  Da y 8 5 ( ± 5) – D os e 7 .................................................................................................. 8 2
1 3. 1 0
Da y 9 9 ( ± 5) or 1 4 Da ys P ost- D os e – F oll o w- u p Visit 1 ............................................ 8 3
1 3. 1 1  Da y 1 4 1 ( ± 5) or 5 6 Da ys P ost- D ose – F oll o w- u p Visit 2 .......................................... 8 4
1 3. 1 2  Da y 1 6 9 ( ± 5)/ E n d of St u d y or 8 4 Da ys P ost- D os e – F oll o w- u p Visit 3 .................... 8 4
1 3. 1 3  E n d of St u d y Defi niti o n .............................................................................................. 8 5
1 4.
A d verse E v e nt R e p orti n g a n d D oc u me nt ati o n ................................................................. 8 5
1 4. 1  A d vers e E v e nts ........................................................................................................... 8 5
1 4. 2  Seri o us A d vers e E v e nts .............................................................................................. 8 6
1 4. 3  A d vers e E v e nts of S pecial I nt erest ............................................................................. 8 7


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 of 1 3 5 
C o nfi d e nti al  
1 4. 4
I nje cti o n- Relate d Reacti o ns ........................................................................................ 8 7
1 4. 5  I njecti o n Site Reacti o ns .............................................................................................. 8 8
1 4. 6
A na p h yla xis ................................................................................................................ 8 8
1 4. 7  E val uati n g A d verse E ve nts a n d Seri o us A d verse E ve nts ........................................... 8 9
1 4. 7. 1
Esta blis hi n g Dia g n osis ................................................................................. 8 9
1 4. 7. 2
Assess me nt of I nte nsit y ................................................................................ 8 9
1 4. 7. 3
Assess me nt of Ca usalit y t o St u d y Dr u g ....................................................... 9 0
1 4. 7. 4
Assess me nt of Ca usalit y t o St u d y Pr oce d ure ............................................... 9 0
1 4. 7. 5
Acti o n Ta ke n ................................................................................................ 9 1
1 4. 7. 6
Assess me nt of O utc o m e ............................................................................... 9 1
1 4. 8  A d vers e E v e nt Re p orti n g Pr oce d ures ......................................................................... 9 1
1 4. 8. 1
All A d v erse E v e nts ....................................................................................... 9 1
1 4. 8. 2
Seri o us A d verse E v e nt Re p orti n g ................................................................ 9 2
1 4. 8. 3
Pre g n a nc y Re p orti n g .................................................................................... 9 3
1 4. 8. 4
A E SI R e p orti n g ............................................................................................ 9 4
1 4. 9  Me dical M o nit ori n g .................................................................................................... 9 4
1 4. 1 0  I n d e pe n d e nt Data M o nit ori n g C o m mittee .................................................................. 9 5
1 4. 1 1  St u d y Wit h dra wal Criteria .......................................................................................... 9 5
1 4. 1 2 St u d y St o p pi n g R ules ................................................................................................. 9 5
1 5.
Disc o nti n u ati o n a n d R e pl a ce me nt of S u bjects .................................................................. 9 6
1 5. 1  Defi niti o n of St u d y C o m pleti o n ................................................................................. 9 6
1 5. 2  Earl y Disc o nti n uati o n of St u d y Dr u g ......................................................................... 9 6
1 6.
St atistic al Met h o ds a n d Ge ner al C o nsi der ati o ns ............................................................. 9 7
1 6. 1  Sa m ple Size ................................................................................................................ 9 7
1 6. 2  A nal ysis P o p ulati o ns .................................................................................................. 9 8
1 6. 3  S u bject Dis p ositi o n ..................................................................................................... 9 8


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 of 1 3 5 
C o nfi d e nti al  
1 6. 4
De m o gra p hic a n d Baseli ne C h aracteristics ................................................................ 9 8
1 6. 5  St u d y Dr u g E x p os ure .................................................................................................. 9 9
1 6. 6
Efficac y A nal ysis ........................................................................................................ 9 9
1 6. 6. 1
Pri mar y Efficac y E n d p oi nt A nal ysis ............................................................ 9 9
1 6. 6. 2
Sec o n dar y Efficac y E n d p oi nt A nal ysis ...................................................... 1 0 0
1 6. 6. 3
E x pl orat or y A nal ysis .................................................................................. 1 0 1
1 6. 6. 4
I nteri m A nal ysis ......................................................................................... 1 0 1
1 6. 7  Safet y A nal ysis ......................................................................................................... 1 0 2
1 6. 7. 1
Treat me nt E mer ge nt A d v erse E ve nts ......................................................... 1 0 2
1 6. 7. 2
A nti- Dr u g A nti b o dies ................................................................................. 1 0 2
1 6. 7. 3
Cli nical La b orat or y Assess me nts ............................................................... 1 0 2
1 6. 7. 4
Vital Si g ns .................................................................................................. 1 0 3
1 6. 7. 5
E C G ............................................................................................................ 1 0 3
1 6. 7. 6
P h ysical E xa m ............................................................................................ 1 0 3
1 6. 7. 7
C o nc o mita nt Me dicati o ns .......................................................................... 1 0 3
1 6. 7. 8
S u bject C o nfi d e nti alit y ............................................................................... 1 0 3
1 7.
D at a C ollecti o n, Rete nti o n, a n d M o nit ori n g ................................................................... 1 0 4
1 7. 1
Data C ollecti o n I nstr u me nts ..................................................................................... 1 0 4
1 7. 2  Data Ma na g e me nt Pr oce d ures .................................................................................. 1 0 4
1 7. 3  Data Q ualit y C o ntr ol a n d Re p orti n g ......................................................................... 1 0 4
1 7. 4  Data base L oc k/ Discl os ure of Ra n d o mizati o n C o de ................................................. 1 0 4
1 7. 5  Arc hi vi n g of D ata ..................................................................................................... 1 0 5
1 7. 6  A vail a bilit y a n d Rete nti o n of I n vesti g ati o nal Rec or ds ............................................. 1 0 5
1 7. 7  M o nit ori n g ................................................................................................................ 1 0 6
1 8.
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 .............................................. 1 0 6
1 8. 1  Pr ot oc ol A me n d me nts .............................................................................................. 1 0 6


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 0 of 1 3 5 
C o nfi d e nti al  
1 8. 2
I n d e pe n de nt Et hics C o m mittees/I nstit uti o nal Re vie w B oar ds ................................. 1 0 7
1 8. 3  I nf or me d C o nse nt F or m ............................................................................................ 1 0 7
1 8. 4
P u blicati o ns ............................................................................................................... 1 0 8
1 8. 5  Cli nical St u d y Re gistrati o n ....................................................................................... 1 0 8
1 8. 6
Pa y me nt t o S u bjects .................................................................................................. 1 0 8
1 8. 7  I n v esti gat or Res p o nsi bilities ..................................................................................... 1 0 9
1 9.
Refere nces .......................................................................................................................... 1 1 0
2 0.
A p pe n di ces ......................................................................................................................... 1 1 2
2 0. 1  A p pe n di x 1: At o pic Der matitis – A merica n A ca de m y of Der m at ol o g y  
C o nse ns us Criteria .................................................................................................... 1 1 3
2 0. 2  A p pe n di x 2: Vali date d I n vesti gat or Gl o bal Assess me nt .......................................... 1 1 4
2 0. 3  A p pe n di x 3: Ecze m a Area a n d Se verit y I n d e x ......................................................... 1 1 5
2 0. 4  A p pe n di x 4: 
 .................................................... 1 2 2
2 0. 5  A p pe n di x 5: 
 ........ 1 2 3
2 0. 6  A p pe n di x 6: 
 .......................................................... 1 2 4
2 0. 7  A p pe n di x 7: At o pic C o n diti o ns Q uesti o n naire ......................................................... 1 2 5
2 0. 8  A p pe n di x 8: C o m m o n Ter mi n ol o g y Criteria f or A d verse E v e nts v. 5. 0 .................. 1 2 6
2 0. 9  A p pe n di x 9: Sa m ps o n’s Criteria of A na p h yl a xis ..................................................... 1 2 7
2 0. 1 0  A p pe n di x 1 0: He patitis B a n d He p atitis C Ser ol o gic Testi n g Details ...................... 1 2 8
2 0. 1 1  A p pe n di x 1 1: O pe n L a bel E xte nsi o n Peri o d ( O pti o nal) ........................................... 1 2 9
2 0. 1 1. 1
S u m mar y of t h e O pe n- L a bel E xte n de d D osi n g Peri o d .............................. 1 2 9
2 0. 1 1. 2
O L E O bjecti ve ............................................................................................ 1 3 0
2 0. 1 1. 3
O L E Eli gi bilit y Criteria .............................................................................. 1 3 0
2 0. 1 1. 4
O L E I ncl usi o n Criteria ............................................................................... 1 3 0
2 0. 1 1. 5
O L E E xcl usi o n Criteria .............................................................................. 1 3 0


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 1 of 1 3 5 
C o nfi d e nti al  
2 0. 1 1. 6
O L E Treat me nt ........................................................................................... 1 3 1
2 0. 1 1. 7
O L E Pr oce d ures a n d G ui deli n es ................................................................ 1 3 1
List of T a bl es
Ta ble 1 
St u d y A K 0 0 2- 0 1 8 Sc he d ule of Assess me nts: D o u ble- Bli n d Peri o d ......................... 4 2
Ta ble 2 
St u d y Dr u g D osa ge .................................................................................................... 6 0
Ta ble 3  
A d verse E v e nt Se verit y per C T C A E ......................................................................... 8 9
Ta ble 4  
A d verse E v e nt Relati o ns hi p t o St u d y Dr u g ............................................................... 9 0
Ta ble 5  
A d verse E v e nt Relati o ns hi p t o St u d y Pr oce d ure ....................................................... 9 1
Ta ble 6  
He patitis B Testi n g .................................................................................................. 1 2 8
Ta ble 7  
He patitis C Testi n g .................................................................................................. 1 2 8
Ta ble 8 
St u d y A K 0 0 2- 0 1 8 Sc he d ule of Assess me nts: O pe n- La bel E xte nsi o n Peri o d ......... 1 3 2
List of Fi g ure 
Fi g ure 1  
St u d y Dia gra m ........................................................................................................... 4 6


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 2 of 1 3 5 
C o nfi d e nti al  
List of A b bre vi ati o ns
A C
Aller gic c o nj u ncti vitis
A C S 
Aller gic C o nj u ncti vitis S y m pt o m(s) 
A D 
At o pic d er matitis 
A D A 
A nti- dr u g-a nti b o d y 
A D C C
A nti b o d y- de p e n d e nt cell ular c yt ot o xicit y
A D L
Acti vities of dail y li vi n g
A E 
A d v erse e ve nt(s) 
A E SI 
A d v erse e ve nt(s) of s p ecial i nterest 
A K C  
At o pic k erat o c o nj u ncti vitis  
A L T 
Ala ni n e a mi n otra nsferase 
A N C O V A 
A nal ysis of c o varia n ce 
a nti- H Bc 
A nti b o d y t o He patitis B c ore a nti g e n 
A nti- H C V 
H e p atitis C vir us a nti b o d y 
A S T
As p artate a mi n otra nsferase
 
 
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 
CI 
C o nfi d e n ce i nter v al
c m 
Ce nti m eter 
C O VI D- 1 9 
C or o n a vir us disease 2 0 1 9 
C S 
Cli nicall y si g nifica nt 
C T C A E 
C o m m o n T er mi n ol o g y Criteria f or A d v erse E ve nts  
C T F G
Cli nical Trials Facilitati o n a n d C o or di n ati o n Gr o u p  
C U 
C hr o nic urticaria 
 
 
E A SI 
E cze ma Area a n d Se verit y I n de x 
E C G 
Electr o car di o gra m
e C R F 
Electr o nic Case Re p ort F or m 
E G 
E osi n o p hilic g astritis 
E LI S A 
E nz y me-li n k e d i m m u n os or be nt assa y 
E o D 
E osi n o p hilic d u o d e nitis (f or merl y referre d t o as e osi n o p hilic gastr o e nteritis) 
E O S
E n d of st u d y


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 3 of 1 3 5 
C o nfi d e nti al  
E T 
E arl y Ter mi n ati 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
G D P R
Ge neral Data Pr otecti o n Re g ulati o n ( E ur o p ea n U ni o n)
G G T 
Ga m m a- gl uta m yl tra nsferase 
G L P 
G o o d L a b orat or y Practice 
H Bs A g 
He p atitis B s urface a nti g e n 
h C G  
h u ma n c h ori o nic g o n a d otr o pi n 
HI P A A 
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act 
HI V 
H u m a n i m m u n o d eficie n c y vir us 
I C F 
I nf or me d c o nse nt f or m 
I C H 
I nter n ati o n al C o u n cil o n Har m o nisati o n 
i D M C 
I n de p e n de nt Data M o nit ori n g C o m mittee 
I E C 
I n d e pe n d e nt Et hics C o m mittee 
I G A 
I n v esti g at or Gl o b al Assess me nt  
I g E
I m m u n o gl o b uli n E
I g G 1
I m m u n o gl o b uli n G 1
I N D 
I n v esti g ati o n al Ne w Dr u g (a p plicati o n) 
I P 
I n v esti g ati o n al pr o d u ct 
I R B 
I nstit uti o n al Re vie w B o ar d 
I R R 
I nf usi o n-relate d reacti o n (f or i ntra ve n o us i nf usi o n) 
I njecti o n-relate d reacti o n (f or s u b c uta n e o us i njecti o n) 
I R T 
I nteracti v e Res p o nse T ec h n ol o g y (s yste m) 
I S M 
I n d ole nt s yste mic m ast o c yt osis 
I TI M 
I m m u n orece pt or t yr osi n e- b ase d i n hi bit or y m otif
I T T 
I nte nt t o treat 
I U D 
I ntra uteri n e d e vice 
I U S 
I ntra uteri ne h or m o n e-releasi n g s yste m 
I V 
I ntra ve n o us 
J A K 
Ja n us ki nase(s)
k g 
Kil o gra m 
L A R C 
L o n g- Acti n g Re v ersi ble C o ntrace pti v es  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 4 of 1 3 5 
C o nfi d e nti al  
L L N 
L o wer li mit of n or m al 
Me d D R A 
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
m g 
Milli gra m 
mI T T 
M o difie d I nte nti o n-t o- Treat 
mI U
Milli-i nter nati o nal u nits
m L 
Milliliter 
m M 
Milli m olar 
M M R M 
Mi x e d m o d el f or re peate d meas ures 
m T O R
m a m m alia n T ar get of Ra p a m yci n 
N CI 
Nati o n al Ca ncer I nstit ute 
N C S 
N ot cli nicall y si g nifica nt  
N O A E L 
N o- o bser ve d-a d verse-effect le vel 
N O E L 
N o- o bser v e d effect le vel
N R S 
N u meric Rati n g Scale 
O S S 
O c ular Si g ns a n d S y m pt o ms 
P D 
P h ar mac o d y na mics  
P D E 4
P h os p h o diesterase- 4
P E F 
Pea k e x pirat or y fl o w 
PI D 
Patie nt i d e ntificati o n n u m b er 
P K 
P h ar mac o ki n etic(s) 
P P 
Per Pr ot o c ol 
 
P R O 
Patie nt re p orte d o utc o m e 
P U V A 
Ps orale n + ultra vi olet A or B ( U V A or U V B) 
Q o L 
Q u alit y of Life 
S A E
Seri o us a d verse e v e nt(s)
S A P 
Statistical A n al ysis Pla n 
S C 
S u b c uta n e o us 
 
 
Si glec 
Sialic aci d- bi n di n g, i m m u n o gl o b uli n-li k e lecti n 
S O C
S yste m or g a n class
T E A E 
Treat me nt-e mer ge nt a d verse e ve nt(s)  
T E A E SI 
Treat me nt-e mer ge nt a d verse e ve nt(s) of s p ecial i nterest  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 5 of 1 3 5 
C o nfi d e nti al  
T N F 
T u m or n ecr osis fact or 
µ L 
Micr oliter 
U L N 
U p p er li mit of n or m al 
U S P 
U nite d States P h ar mac o p eia
U V A
Ultra vi olet A
U V B 
Ultra vi olet B 
 
 
vI G A 
Vali d ate d I n vesti g at or Gl o bal Assess me nt  
V K C
Ver nal c o nj u ncti vitis
w/ v 
Wei g ht/ V ol u me 
W O C B P 
W o me n of c hil d beari n g p ote ntial 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 6 of 1 3 5 
C o nfi d e nti al  
1.
Pr ot oc ol S y n o psis 
Title:  
A P hase 2 Ra n d o mize d, D o u bl e- Bli n d, Place b o- C o ntr oll e d St u d y t o E val uat e 
t h e Efficac y a n d Safet y of S u bc uta ne o us Lire nteli ma b i n A d ult S u bj ects wit h 
M o derate-t o- Se vere At o pic Der matitis I na de q uat el y C o ntr oll e d b y T o pical 
Treat me nts 
S p o ns or:  
Alla k os I nc. 
N u m ber of Sites:   
U p t o 7 0 sites i n t he U nite d St ates a n d Ger m a n y 
N u m ber of S u bjects:  
A p pr o xi m at el y 1 3 0 
N o ncli nic al B ac k gr o u n d 
Lire nteli ma b 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 direct e 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 sel ecti vel y o n t he s urface of 
mat ure e osi n o p hils a n d mast cells, b ut n ot i n earl y prec urs ors of t hese cell p o p ulati o ns. I n bl o o d, 
bi n di n g of lire nteli ma b t o Si glec- 8 i n d uces a nti b o d y- de pe n de nt cell ular c yt ot o xicit y ( A D C C) a gai nst 
e osi n o p hils, l ea di n g t o ra pi d a n d s ustai ne d de pl eti o n of t hese cells fr o m t he circ ulati o n. I n t he tiss ue, 
lire nteli m a b i n d uces direct a p o pt osis of e osi n o p hils a n d i n hi biti o n of mast cells. 
Lire nteli ma b has bee n pr o d uce d i n 2 f or m ulati o ns: 1 f or i ntra ve n o us i nf usi o n (lire nteli m a b I V) a n d 1 f or 
s u bc uta ne o us i njecti o n (lire nt eli ma b S C) (see Test Pr o d uct, D ose, a n d A d mi nistrati o n). 
Cli nic al B ac k g r o u n d 
Lire nteli ma b I V, a d mi nistere d e v er y 4 wee ks, has bee n pre vi o usl y teste d i n o ver 7 0 0 healt h y v ol u nt eers 
a n d patie nts wit h i n d ole nt s yste mic mast o c yt osis (I S M), c hr o nic urti caria ( C U), se vere aller gi c 
c o nj u ncti vitis ( A C), mast cell g astritis, a n d e osi n o p hilic gastritis ( E G) a n d/ or e osi n o p hilic d u o de nitis 
( E o D). M ulti ple d oses of 3 m g/ k g ha ve bee n gi ve n t o patie nts wit h I S M, C U, A C, mast cell gastritis, 
a n d E G a n d/ or E o D.  
I n ge neral, lire nteli ma b I V has bee n well t olerat e d. T he m ost c o m m o n treat me nt-e mer ge nt a d verse 
e ve nts ( T E A E) o bser ve d were i nf usi o n-relate d reacti o ns (I R R). T he I R R were m ostl y mil d t o m o derate 
a n d occ urre d m ost ofte n d uri n g t he first i nf usi o n. I R R t hat were dee m e d m ore seri o us t y pi call y res ol v e d 
wit hi n 2 4 h o urs, a n d a d diti o nal c ortic oster oi ds a n d/ or a nti hista mi nes were use d i n cases w he n sl o wi n g 
t h e rate of i nf usi o n a n d a d diti o nal s u p p orti ve care al o ne di d n ot res ol ve t he iss ue. C o m m o n s y m pt o ms 
of I R R were hea dac he, na usea, s weati n g, fl us hi n g, a n d re d ness. M ost I R R t hat occ urre d 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 h e i nf usi o n, wit h mi ni m al 
i nter ve nti o n. T he ris k of I R R has bee n s u bsta ntiall y re d uce d b y a d mi nistrati o n of a si n gl e d ose of 
oral c ortic oster oi d (e. g., pre d nis o ne 6 0 m g) gi ve n orall y 1 2 t o 2 4 h o urs pri or t o t he first d ose of 
lire nteli m a b I V.  
St u d y A K 0 0 2- 0 1 7 e val uat e d t h e p har m ac o ki netics ( P K) a n d p har mac o d y na mics ( P D) of lire nteli m a b I V 
a n d S C i n healt h y v ol u nteers. S u bjects recei v e d 0. 3, 1, 3, or 5 m g/ k g or a fi xe d d ose of 3 0 0 m g or 
4 5 0 m g lire nteli m a b S C, or 1 m g/ k g or 3 m g/ k g lire nteli ma b I V. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 7 of 1 3 5 
C o nfi d e nti al  
Cli nic al B ac k g r o u n d c o nt. 
I n eac h of t he S C c o h orts, 8 s u bjects were ra n d o mize d t o lire nteli ma b ( 6 per gr o u p) or place b o ( 2 per 
gr o u p) i n a d o u ble- bli n d ma n ner; 1 2 s u bjects recei ve d lire nteli m a b I V ( 6 s u bjects per gr o u p) i n a n o pe n-
la bel ma n ner.  
T he st u d y s h o we d t hat t he P D effect ( de pleti o n of bl o o d e osi n o p hils) occ urre d wit hi n 1 h o ur of d osi n g 
a n d laste d f or at l east 1 m o nt h at I V a n d S C d oses of 1 m g/ k g a n d f or 3 m o nt hs at all hi g her I V a n d S C 
d oses. T he S C i njecti o ns were well t olerate d, a n d n o i nj ecti o n site reacti o ns or ge neral i njecti o n 
reacti o ns were n ote d at a n y d ose de m o nstrati n g s uita bilit y f or f urt her e val uati o n.  
I n St u d y A K 0 0 2- 0 0 5 i n patie nts wit h se vere A C, lire nteli m a b de m o nstrate d cli nical acti vit y i n relie vi n g 
t h e si g ns a n d s y m pt o ms of se vere A C acr oss all m eas ure d d o mai ns. T he st u d y s h o we d a 6 1 % 
i m pr o ve m e nt i n patie nt-re p orte d oc ular s y m pt o ms (t otal aller gic c o nj u ncti vitis s y m pt o ms [ A C S]) a n d 
7 9 % of s u bjects were dee me d res p o n ders at 2 wee ks f oll o wi n g t he fi nal lire nteli ma b d ose c o m pare d t o 
baseli ne. I n vesti gat or-assesse d oc ul ar si g ns a n d s y m pt o ms (t otal O S S) als o i m pr o ve d b y 5 3 %, a n d 8 3 % 
of s u bjects were dee me d res p o n ders at t he fi nal d ose ti me p oi nt c o m p are d t o baseli ne. A d diti o nall y, 
s y m pt o m b ur de n was assesse d acr oss m ulti ple at o pi c c o m or bi dities, a n d s y m pt o m s e verit y decrease d 
s u bst a nti all y acr oss all c o n diti o ns assesse d, i ncl u di n g i n at o pic der matitis ( A D), ast h ma, a n d r hi nitis. 
T he lac k of treat me nt-relate d a d verse e ve nts ( A E) be y o n d I R R i n t he I V st u dies c o m bi ne d wit h t he 
cli ni cal acti vit y o bser ve d i n treati n g m ulti ple all er gic c o n diti o ns a n d t he ret ur n of si g ns a n d s y m pt o ms 
off treat me nt ma ke lire nteli m a b a p ote nti all y pr o misi n g ca n di date f or m ulti ple e osi n o p hil a n d m ast cell-
dri ve n i nfla m mat or y dis eases, i ncl u di n g A D. 
T a r get Dise ase B ac k gr o u n d a n d R ati o n ale f or t he St u d y 
At o pic der matitis is a c hr o nic pr uritic i nfl a m m at or y der m atitis t hat affects a p pr o xi m atel y 1 6. 5 milli o n 
( 7. 3 %) a d ults i n t he U S, of w hi c h ar o u n d 6. 6 milli o n ( 4 0 %) ha ve m o derate-t o-s e vere disease. T he 
pat h o ge nesis of A D is c o m ple x a n d i n v ol ves a b n or maliti es i n s ki n barrier f u ncti o n, altere d s ki n fl ora, 
a n d i m m u ne d ysre g ul ati o n ( F u xe nc h, 2 0 1 9). T here is i ncrease d e x pressi o n of T h 2 a n d T h 2 2 c yt o ki nes 
li ke I L- 4, I L- 1 3, I L- 3 1, a n d I L- 2 2. Mast cell n u m bers are el e vat e d i n t he s ki n of A D patie nts. T hese 
cells, b y virt ue of pr o d uci n g pr urit o ge nic me diat ors li ke hista mi ne, tr y ptase a n d I L- 3 1, mi g ht c o ntri b ute 
t o A D s y m pt o ms. I n a d diti o n, mast cells ma y c o ntri b ute t o ne ur o ge ni c i nfla m mati o n b y i nteracti n g wit h 
se ns or y ner ves. I n a d diti o n t o mast cells, e osi n o p hils ma y be ele vate d i n pati e nts wit h A D. It has bee n 
de m o nstrate d t hat e osi n o p hils t a ke n fr o m A D bi o psies are acti vate d a n d s h o w dela ye d pr o gra m m e d cell 
deat h. Ta ke n t o get her, t h ese fi n di n gs s u g gest t h at acti vati o n a n d de gra n ulati o n of mast cells a n d 
e osi n o p hils m a y be a maj or c o m p o ne nt i n t he pat h o ge nesis of A D a n d ma y re prese nt s uita ble tar gets f or 
t h era pe utic i nt er ve nti o n. 
At o pic der matitis patie nts t y picall y e x peri e nce dr y s ki n a n d i nte nse pr urit us, w hi c h ca n l ea d t o 
de vel o p me nt of er yt h e m at o us pa p ules wit h e x u dati o n, cr usti n g, a n d e xc oriati o n. A rece nt st u d y of 
a d ults wit h m o derate-t o-se vere A D f o u n d t hat 7 0. 5 % re p orte d se vere, u n beara ble itc h i n t he past 
2 wee ks, 8 5. 8 % re p orte d dail y itc h, a n d 6 2. 8 % re p orte d itc hi n g at least 1 2 h o urs per da y. C hr o nicall y, 
t his ofte n lea ds t o s ki n t hic ke ni n g a n d lic he nificati o n, m ost c o m m o nl y i n s ki n fle x ures.  
 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 1 8 of 1 3 5 
C o nfi d e nti al  
T a r get Dise ase B ac k gr o u n d a n d R ati o n ale f or t he St u d y c o nt.
At o pic der matitis ma y i n v ol v e t he face, nec k, tr u n k, a n d e xtre mities. At o pic der matitis f oll o ws a 
c hr o nic rel a psi n g c o urs e a n d ca n be c o m pli cate d b y de v el o p m e nt of bacterial a n d viral s ki n i nfecti o ns. 
Patie nts wit h A D als o ha ve a n i ncrease d ris k of aller gic r hi nitis, ast h ma, f o o d aller gi es, a n d oc ular 
c o n diti o ns li ke at o pic kerat oc o nj u n cti vitis ( A K C) a n d ver nal c o nj u ncti vitis ( V K C). 
T he mai n g oals of A D treat me nt are t o mai nt ai n a de q uate s ki n h y drati o n, re d uce pr urit us, a n d pre ve nt 
e xacer bati o ns. W hile oral a nti- hista mi nic a ge nts ma y hel p re d uce pr urit us, t o pical a ge nts are t he 
mai nsta y of treat m e nt. T hese i n cl u de m oist urizi n g/e m ollie nt pre parati o ns, w hic h pr otect t h e s ki n barrier 
a n d pre ve nt wat er l oss. Al o n g wit h m oist uri zi n g a ge nts, t o pical a nti-i nfla m m at or y a ge nts s uc h as 
c orti c oster oi ds a n d calci ne uri n i n hi bit ors (e. g., tacr oli m us a n d pi m ecr oli m us) are use d f or mil d-t o-
m o derat e dis ease as sec o n d li ne o pti o ns. Crisa b or ole, a t o pical p h os p h o diesterase 4 ( P D E 4) i n hi bit or, 
was a p pr o ve d b y t he F D A i n Dece m ber 2 0 1 6, a n d is use d f or treat me nt of mil d-t o- m o derate A D.  
W hil e t o pical a ge nts ca n be effecti v e i n mil d-t o- m o derate disease, t here are l o n g ter m safet y c o ncer ns. 
T o pical ster oi ds ca n ca us e s ki n atr o p h y a n d p ossi ble a dre nal s u p pressi o n d ue t o s yste mic a bs or pti o n. 
Tacr oli m us a n d pi mecr oli m us carr y a p ote nti al ris k of s ki n ca ncer, w hic h has res ulte d i n a blac k b o x 
war ni n g b y t he F D A.  
T he ma na ge me nt of m o derate-t o-s e vere dis ease is m ore diffi c ult. Patie nts ca n be treat e d wit h 
p h ot ot hera p y ( 3 ti mes per wee k), w hi c h is c u m bers o me, e x pe nsi ve, a n d ma y i ncrease t he ris k of 
de vel o pi n g s ki n ca ncer. Oral c ortic oster oi ds are occasi o nall y use d b ut are li mite d b y si de effects 
i n cl u di n g i ncrease d ris k of dia bet es, h y perte nsi o n, a dre nal s u p pressi o n, a n d e ye diseases li ke gla uc o ma 
a n d cat aracts. A n oral calci ne uri n i n hi bit or (c ycl os p ori n) ca n be use d b ut re q uires fre q ue nt m o nit ori n g 
of dr u g le vels a n d carries ris ks of h y perte nsi o n, ne p hr ot o xicit y, h y pertric h osis, a n d g u m h y per pl asia. 
Als o, l o n g-t er m us e of st er oi ds a n d c ycl os p ori n lea ds t o i m m u n os u p pressi o n a n d i ncrease d ris k of 
i nfecti o ns.  
I n M arc h 2 0 1 7, t he F D A a p pr o ve d d u pil u ma b f or t he treat me nt of a d ult patie nts wit h m o derate-t o-
se vere A D n ot a de q uatel y c o ntr oll e d wit h t o pi cal prescri pti o n t hera pi es or w he n t h os e t hera pies are n ot 
a d visa ble. D u pil u m a b is a f ull y h u ma n m o n ocl o nal a nti b o d y t hat bi n ds t o t he al p ha s u b u nit of t he I L- 4 
rece pt or a n d i n hi bits si g nali n g of I L- 4 a n d I L- 1 3, alteri n g T-cell me diate d i m m u ne res p o nse, w hic h is 
belie ve d t o pla y a r ol e i n A D. T he l o n g-t er m ( 5 2 wee k) safet y a n d efficac y of d u pil u ma b was e val uate d 
i n a 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. C o nc o mit a nt use of t o pi cal c ortic oster oi ds 
(a n d t o pi cal cal ci ne uri n i n hi bit ors, if i n dicate d) was all o we d. 
I n t he d u pil u ma b st u d y, at Wee k 5 2, m ore patie nts i n t he d u pil u ma b-treate d gr o u p ac hie ve d t he 
I n vesti gat or Gl o bal Assess m e nt (I G A) a n d Ecze ma Area a n d Se verit y I n de x ( E A SI)- 7 5 e n d p oi nts t h a n 
t h e place b o-treat e d gr o u p (a p pr o xi m atel y 4 0 % vers us 1 3 % a n d 6 5 % vers us 2 2 %, res pecti v el y). 
H o we ver, t h e d u pil u ma b-treate d patie nts ha d a 2-f ol d hi g her i nci de nce of e ye dis or ders i ncl u di n g 
n o n-i nfecti o us c o nj u ncti vitis. T here c o nti n ues t o be a s u bsta ntial nee d f or ne w a n d better treat me nts f or 
m o derat e-t o- se vere A D. B y re d uci n g e osi n o p hil n u m bers a n d bl oc ki n g m ast cell acti vati o n, lire nteli m a b 
ma y be usef ul i n t he treat me nt of patie nts wit h A D. 
 




Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 2 0 of 1 3 5 
C o nfi d e nti al  
S a m ple Size c o nt.
T o detect a treat me nt differe nce of 2 9 %, t he n u m ber of s u bjects re q uire d f or 9 0 % p o wer is 5 5. 
H o we ver, t o acc o u nt f or a n a ntici pate d 1 0 % dr o p o ut rate, t he s a m ple size will be i ncrease d t o 6 5 per 
treat me nt gr o u p.  
E nr oll me nt will be m o nit ore d t o li mit t h e i m p act of ra n d o mizi n g a dis pr o p orti o natel y lar ge n u m ber of 
s u bj ects wit h a n E A SI sc ore i n t h e l o wer ra n ge, refl ecti n g m ore m o derate diseas e o nl y (i.e., E A SI s c ore 
< 2 2). T his will als o pr o vi de a s u bject p o p ulati o n wit h a f ull ra n ge of E A SI sc ores c o nsiste nt wit h t he 
i nte nt t o st u d y lire nteli m a b i n m o derate-t o-se vere A D dis ease.
St u d y Desi g n
T his P hase 2, pr o of- of-c o nce pt, ra n d o mi ze d, d o u ble- bli n d, place b o-c o ntr oll e d st u d y will i n vesti gate 
t h e efficac y a n d safet y of lire nteli ma b S C i n a d ult s u bjects wit h m o derate-t o-s e vere A D i na de q uatel y 
c o ntr olle d b y t o pical treat me nts. A p pr o xi matel y 1 3 0 s u bjects will be e nr olle d i n u p t o 7 0 sit es i n t he U S 
a n d Ger ma n y a n d will be ra n d o mi ze d 1: 1 t o recei ve eit her 7 S C i njecti o ns of place b o or lire nteli ma b 
a n d t he n f oll o we d f or 1 2 wee ks after t he last d ose. S u bj ects will be gi v e n t he o pti o n t o e nr oll i nt o a n 
o pe n-l a bel e xte nsi o n ( O L E) peri o d of t he st u d y after c o m pleti n g t he Da y 9 9 visit of t he d o u ble- bli n d 
peri o d. S u bjects c h o osi n g n ot t o e nter t he O L E peri o d will c o nti n ue t o be f oll o we d i n t h e d o u ble- bli n d 
peri o d of t he st u d y f or 1 2 wee ks aft er t he last d ose. 
Base d o n t he fee d bac k fr o m at o pic der matitis e x perts a n d c o m pl ete d feasi bilit y assess me nts, it is 
e x pect e d t hat eac h site will be a ble t o scree n t hree s u bjects a n d e nr oll t w o of t he m i n t he d urati o n of t h e 
e nr oll me nt peri o d. E nr oll me nt is c o nsi dere d t o be c o m petiti ve. T o e ns ure t he e nr oll me nt g oal is 
ac hie ve d i n a ti mel y m a n ner, u p t o 7 0 sites (a p pr o xi mat el y 5 5 i n t he U S a n d a p pr o xi matel y 1 5 i n 
Ger ma n y) will be i nitiate d. If st u d y e nr oll me nt rate ca n be ac hie ve d wit h fe wer sites i n or der t o m eet t he 
st u d y ti meli ne, t he n fe wer sit es ma y be nee de d. 
S u bjects will be c o nse nte d a n d scree ne d, a n d t h ose w h o meet eli gi bilit y crit eri a ca n be e nr olle d i n t he 
st u d y. S u bjects 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 oll e d ma y be assi g ne d a ne w pati e nt i de ntificati o n n u m ber a n d rescree ne d o nce. S u bjects 
rescree ne d wit hi n 3 0 da ys of si g ni n g t he i nitial i nf or me d c o nse nt f or m (I C F) will n ot nee d t o si g n a ne w 
I C F if t here h a ve bee n n o c ha n ges t o t h e I C F. 
S u bjects will be scree ne d f or a p pr o xi matel y 2 wee ks (- 1 4 da ys) pri or t o d ose a d mi nistrati o n. D uri n g 
scree ni n g a n d t hr o u g h vari o us ti me p oi nts d uri n g t he st u d y, t he E A SI, I G A, 
 
 
 assess m e nts will be c o m plete d. A d diti o nal q uesti o ns will be as ke d a b o ut 
s y m pt o ms relate d t o ast h ma, aller gic r hi nitis, a n d aller gi c c o nj u ncti vitis t hat s u bjects wit h t h e at o pi c 
c o n diti o n(s) ma y ha ve o n Da y 1, Da y 9 9, a n d O L E Da y 9 9 ( At o pic C o n diti o ns Q uesti o n naire). 
Certai n me dicati o ns are pr o hi bite d d uri n g t he st u d y. Use of s yste mi c a n d/ or t o pical c ortic oster oi ds, 
calci ne uri n i n hi bit ors, J A K i n hi bit ors, t o pical P D E 4 i n hi bit ors (crisa b or ole), d u pil u ma b, or 
tral o ki n u m a b are pr o hi bit e d d uri n g t he st u d y. S u bjects w h o are o n a n y t o pi cal c orti c oster oi ds, t o pical  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 2 1 of 1 3 5 
C o nfi d e nti al  
St u d y Desi g n c o nt.
calci ne uri n i n hi bit ors, t o pical J A K i n hi bit ors, or P D E 4 i n hi bit ors at t he ti me of s cree ni n g m ust 
dis c o nti n ue t hese at t he first scree ni n g visit. 
Bi ol o gi cs or me dicati o ns t hat m a y i nterfere wit h t he st u d y s afet y or efficac y assess m e nts s uc h as 
s yste mi c 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 or bi ol o gics a n d s yste mic c orti c oster oi ds 
m ust be disc o nti n ue d pri or t o t he first scree ni n g visit (see Secti o n  8. 5 E xcl usi o n Criteria) a n d are 
pr o hi bit e d t hr o u g h o ut t he st u d y. 
D uri n g t he last 7 da ys pri or t o Da y 1 (t h e first da y of st u d y dr u g d osi n g), t he s u bj ect m ust ha ve use d, at 
least t wice dail y, o nl y n o n- me dicate d t o pi cal t hera p y (i.e., e m ollie nt) wit h o ut ot her acti ve i n gre die nts 
i n dicate d t o treat A D or ot her a d diti ves, w hic h c o ul d affect A D (e. g., h yal ur o nic aci d, urea, cera mi d e, or 
fila g gri n de gra dati o n pr o d ucts). If a s u bject is n ot usi n g a n y e m olli e nt at t he ti me of scree ni n g, a 
s uit a ble n o n- me dicat e d, n o n- prescri pti o n e m olli e nt will be rec o m m e n de d b y t h e I n vesti gat or. 
Eli gi ble s u bjects w h o meet s electi o n criteria at scree ni n g a n d at baseli ne will recei ve t he first d ose of 
lire nteli m a b S C or place b o S C o n Da y 1. S u bjects will recei ve 6 m ore d oses o n Da ys 1 5, 2 9, 4 3, 5 7, 7 1, 
a n d 8 5. 
S u bjects will be gi ve n t he o pti o n of e nteri n g a n O L E peri o d of t h e st u d y after c o m pleti n g t h e Da y 9 9 
visit of t he d o u ble- bli n d peri o d of t he st u d y, c o nti n ge nt o n m eeti n g defi ne d st u d y selecti o n criteria. 
S u bjects n ot e nteri n g t he O L E p eri o d will be f oll o we d f or 1 2 wee ks aft er t he last d ose i n t he 
d o u ble- bli n d peri o d.  
T he pri mar y e n d p oi nt will be assesse d at Wee k 1 4, i.e., 2 wee ks f oll o wi n g t he last d ose i n t he d o u ble-
bli n d peri o d of t h e st u d y. 
Ra n d o mi zati o n will be stratifie d base d o n I G A 3 vs. 4 a n d o n bi ol o gic stat us, naï ve vs. e x p ose d. 
A p pr o xi m atel y 4 0 % of t he st u d y p o p ul ati o n will be s u bj ects wit h a n I G A of 4. 
Fres h bi o psies of lesi o nal a n d n o n-lesi o nal s ki n ma y be c ollecte d fr o m s u bjects pre d ose a n d p ost- d ose at 
selecte d U S sites. Pr o vi di n g bi o psies is o pti o nal, a n d s u bjects will si g n a se parat e c o nse nt f or m f or 
bi o ps y c oll ecti o n. 
Pri m ar y O bjecti v e a n d E n d p oi nt 
T he pri mar y o bjecti ve of t he st u d y will be t o c haract erize t he effi cac y of lire nteli ma b S C i n a d ult 
s u bj ects wit h A D as assesse d b y t he differe nce i n t he pr o p orti o n of s u bj ects w h o ac hie ve E A SI- 7 5 at 
Wee k 1 4. 
Sec o n d ar y O bjecti ves a n d E n d p oi nts 
T o f urt her c haracteri ze t he effi cac y of lire nteli ma b S C i n a d ult s u bjects wit h A D as meas ure d b y t he 
f oll o wi n g: 
 
% C ha n ge i n E A SI fr o m baseli n e t o Wee k 1 4. 
 




Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 2 3 of 1 3 5 
C o nfi d e nti al  
S u bject Selecti o n Criteri a – I ncl usi o n Criteri a c o nt.
3) 
C hr o nic A D (as defi ne d b y t h e A meri ca n Aca de m y of Der mat ol o g y C o nse ns us Crit eria) 
( Eic he nfiel d, 2 0 1 4) t h at has bee n prese nt f or at least 3 years b ef ore s cree ni n g visit.  
4) 
D o c u me nt e d rece nt hist or y of i na de q uate res p o nse t o treat me nt wit h t o pical me dicati o ns s uc h as 
t o pical c ortic ost er oi ds, calci ne uri n i n hi bit ors, J A K i n hi bit ors, or P D E 4 i n hi bit ors (crisa b or ole) f or 
at least 4 wee ks i n t he 6 m o nt hs pri or t o scree ni n g, or s u bjects f or w h o m t hese t o pical treat me nts 
are ot her wise me dicall y i na d vis a bl e (e. g., beca use of si de effects or safet y ris ks). 
5) 
S u bject w h o are bi ol o gic- naï v e or bi ol o gic-e x p ose d. Bi ol o gi c-e x p ose d i ncl u des s u bjects w h o ha ve 
de m o nstrate d sec o n dar y l oss of res p o nse, i nt olera nce, or lac k of access t o bi ol o gics d ue t o 
ec o n o mic reas o ns. 
6) 
 
7) 
I n v ol ve m e nt of at least 1 0 % or m ore of B S A at s cree ni n g a n d at baseli ne. 
8) 
A n I G A s c ore of 3 or a b o ve o n a scale fr o m 0 – 4 at scree ni n g a n d at baseli ne. 
9) 
T he s u bj ect s h o ul d ha ve a p plie d a sta ble d ose of n o n- m e dicat e d, n o n- prescri pti o n, t o pical e m olli e nt 
at least t wi ce d ail y f or 7 c o nsec uti ve da ys i m me di atel y bef ore t he baseli ne visit. 
1 0) 
Willi n g t o a p pl y a sta ble d ose of n o n- m e dicate d, n o n- prescri pti o n, t o pical e m ollie nt, as 
rec o m me n de d b y t he I n vesti gat or at least t wice d ail y f or t he d urati o n of t he st u d y, if n ot alrea d y o n 
a n e m ollie nt at t he ti me of scree ni n g.  
1 1) C o m mit me nt t o re mai n o n t he sa me d ose(s) of A D m e dicati o n(s), i ncl u di n g t o pical e m ollie nts, f or 
t h e e ntire d urati o n of st u d y p arti ci pati o n u nless d ose m o dificati o n is d ue t o u nf ores ee n me dical 
necessit y. 
1 2) 
Willi n g a n d a ble t o c o m pl y wit h t h e st u d y pr oce d ures a n d visit sc he d ule i ncl u di n g f oll o w- u p visits. 
1 3) Fe male s u bjects m ust be eit h er p ost me n o pa usal ( defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati v e me dical ca use) wit h F S H l e vel > 3 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 bil at eral 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 v e ser u m pre g na nc y test a n d a gree t o use a hi g hl y effecti ve m et h o d of 
c o ntrace pti o n as defi n e d i n t his pr ot oc ol or a bstai n fr o m se x ual acti vit y, if c o m plia nt wit h preferre d 
a n d us ual lifest yl e of t he s u bject, 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 hi c he ver is l o n ger. 
s u bj ect will be re q uire d t o ha ve a ne gati ve ser u m pre g na nc y test d uri n g t he scree ni n g peri o d a n d 
will als o be re q uire d t o ha ve a ne gati v e uri ne di pstic k pre g na nc y test pri or t o d osi n g a n d at eac h 
st u d y visit. 
1 4) 
M ale s u bjects wit h fe m al e part ners of c hil d beari n g p ote nti al 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 as d efi ne d i n t his pr ot o c ol or a bst ai 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 h e last d ose of st u d y dr u g, w hic he ver is l o n ger. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 2 4 of 1 3 5 
C o nfi d e nti al  
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 di at el y if t he y s us pect t heir part ner mi g ht be pre g na nt (e. g., misse d or late 
me nstr ual peri o d) at a n y ti m e d uri n g st u d y partici pati o n. 
E x cl usi o n Criteri a:  S u bjects 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) 
C urre nt use of bi ol o gics f or a n y i n dicati o n. 
2) 
De m o nstrate d lac k of pri mar y res p o ns e t o treat me nt wit h a bi ol o gic f or t he treat me nt of A D 
defi ne d as n o res p o nse t o treat me nt des pite c o m plete a d here nce t o t he prescri be d re gi m e n f or at 
least 3 m o nt hs ( pri m ar y n o n-res p o n ders). 
3) 
Us e of a n y of t he f oll o wi n g treat me nts wit hi n 4 wee ks pri or t o t he bas eli n e visit or a n y c o n diti o n 
t h at i n t h e o pi ni o n of t he I n vesti gat or is li k el y t o re q uire s uc h treat me nt(s) d uri n g t he first 4 wee ks 
of st u d y treat me nt: 
–
P h ot ot hera p y f or A D 
–
I m m u n os u p pressi ve or i m m u n o m o d ul at or y dr u gs, i ncl u di n g b ut n ot li mite d t o s yste mic 
calci ne uri n i n hi bit ors (e. g., c ycl os p ori n, tacr oli m us), m T O R i n hi bit ors (e. g., sir oli m us, 
e ver oli m us), a nti- meta b olites (e. g., azat hi o pri ne, met h otre xate, 6- merca pt o p uri ne, lefl u n o mi d e, 
m y c o p he n olate m ofetil), al k ylati n g a ge nts (e. g., c ycl o p h os p ha mi de), e osi n o p hil- de pleti n g 
dr u gs (e. g., pra mi pe x ole), a n d s yste mic c orti c oster oi ds 
–
Oral J A K i n hi bit ors wit hi n 8 wee ks of baseli ne visit (re q uires disc ussi o n wit h Alla k os Me dical 
M o nit or pri or t o s u bject e nr olli n g i n st u d y) 
4) 
Treat me nt wit h bi ol o gics: 
–
A n y cell- de pleti n g a ge nts i ncl u di n g b ut n ot li mite d t o rit u xi ma b wit hi n 6 m o nt hs pri or t o t he 
baseli ne visit or u ntil l y m p h oc yte c o u nt ret ur ns t o n or mal, w hi c he ver is l o n ger 
–
T N F i n hi bit ors (e. g., i nfli xi ma b, a dali m u m a b) a n d ot her bi ol o gics (e. g., d u pil u ma b, 
o maliz u ma b, et c.) wit hi n 5 half-li ves, if k n o w n, or 8 wee ks pri or t o t h e bas eli ne visit, 
w hic he ver is l o n ger 
5) 
A n y use of t o pical c ortic oster oi ds, t o pical cal ci ne uri n i n hi bit ors, t o pical J A K i n hi bit ors (e. g., 
r u x oliti ni b), or t o pical P D E 4 i n hi bit ors (crisa b or ole) f or t he treat me nt of A D wit hi n 1 wee k pri or t o 
t h e baseli ne visit. 
6) 
Re g ular use ( m ore t ha n 2 visits per wee k) of a ta n ni n g b o ot h/ parl or wit hi n 4 wee ks of t he scree ni n g 
visit. 
7) 
Treat me nt wit h c he 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) 
Prese nce of s ki n c o m or bi diti es/c o nc o mit a nt c o n diti o ns t hat ma y i nterfere wit h st u d y assess m e nts 
or i nt er pretati o n of st u d y res ults. 
9) 
Pla n ne d or a ntici pat e d use of a n y pr o hi bite d me dicati o n. 
1 0) Hist or y of mali g na nc y e xce pt carci n o ma i n sit u i n t he cer vi x, earl y-sta ge pr ostate ca ncer, or 
n o n- mela n o ma s ki n ca ncers.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 2 5 of 1 3 5 
C o nfi d e nti al  
S u bject Selecti o n Criteri a – E xcl usi o n Criteri a c o nt.
1 1) A n y disease, c o n diti o n ( me di cal or s ur gical), or car diac a b n or malit y t hat i n t he o pi ni o n of t h e 
I n vesti gat or w o ul d place t he s u bj ect at i ncrease d ris k. 
1 2) A hel mi nt h parasitic i nfecti o n dia g n ose d wit hi n 6 m o nt hs pri or t o t he dat e i nf or me d c o nse nt is 
o btai ne d t hat has n ot bee n treate d wit h or has faile d t o res p o n d t o sta n dar d- of-care t hera p y. 
1 3) E vi de nce of acti ve he p atitis B or C at scree ni n g b ase d o n ser ol o g y. 
1 4) E vi de nce of acti ve HI V i nfecti o n at scree ni n g base d o n ser ol o g y. 
1 5) 
W o me n w h o are pre g na nt, breastfee di n g, or pla n ni n g t o bec o me pre g na nt w hile partici pati n g i n t h e 
st u d y. 
1 6) Prese n ce of a n a b n or m al scree ni n g l a b orat or y val u e c o nsi dere d t o be cli nicall y si g nifi ca nt b y t he 
I n vesti gat or. 
1 7) K n o w n or s us pecte d 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 t hat i n t he 
o pi ni o n of t he I n vesti gat or ma y i nterfere wit h st u d y parti ci pati o n or ass ess me nts. 
1 8) Pri or e x p os ure t o lire nteli ma b or 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. 
1 9) 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 st u d y dr u g a d mi nistrati o n ( 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). 
2 0) S u bj ects w h o wei g h < 4 0 k g at scree ni n g. 
2 1) A n y ot h er reas o n t hat i n t he o pi ni o n of t he I n vesti gat or or t he Me dical M o nit or ma kes t he s u bj ect 
u ns uit a ble f or e nr oll me nt. 
2 2) 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 ( 4 m o nt hs) of st u d y 
dr u g a d mi nistrati o n.  
N ote: 
T his e xcl usi o n criteri o n d oes n ot a p pl y t o all t y pes a n d f or m ulati o ns of v acci nes (i ncl u di n g 
li ve atte n uate d vacci nes) c urre ntl y a ut h orize d/a p pr o ve d b y F D A or ot h er re g ulat or y 
a ut h orit y f or t he pre ve nti o n of C O VI D- 1 9, w hic h ma y be a d mi nistere d bef ore, d uri n g, or 
after t he st u d y.  
  
T he vacci ne s h o ul d n ot be a d mi nistere d wit hi n 3 da ys bef ore a n d wit hi n 3 da ys after 
t h e a d mi nistrati o n of lire nteli ma b s o t hat a n y si de effects ca use d b y eit her of t he 
2 me dicati o ns ca n be m ore easil y deter mi ne d. 
2 3)  E m pl o yees or rel ati ves of t he S p o ns or or t he I n vesti gat or, or ot her pers o ns de pe n de nt o n t h e 
S p o ns or or t h e I n vesti gat or. 
2 4)  C o m mit me nt t o a n i nstit uti o n b y or der iss ue d eit her b y t he j u dicial or t he a d mi nistrati ve a ut h orities. 
 






Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 2 8 of 1 3 5 
C o nfi d e nti al  
S afet y E v al u ati o ns
Safet y a n d t ol era 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 u ati n g A E, 
i n cl u di n g reacti o ns t o t he S C i nj ecti o n. All T E A E will be c oll ecte 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 6 9 ( ± 5 da ys) or Earl y Ter mi nati o n ( E T).  
Se verit y will be assesse d usi n g t he Nati o n al 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 verse E ve nts ( C T C A E) ta bles a n d t o xicit y gra di n g scale ( versi o n 5 or t h e c urre nt versi o n). All A E 
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 h er 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 ni cal la b orat or y t ests c o m prisi n g a nti- dr u g a nti b o d y ( A D A) t o 
lire nteli m a b S C, c o m plete bl o o d c o u nts, c he mistries, a n d uri nal yses; p h ysical e xa ms; a n d vit al si g n 
meas ure me nts. 
T he Me di cal M o nit or will re vie w bli n de d safet y data t hr o u g h o ut t he st u d y.
P h ar m ac o d y n a mic E v al u ati o ns 
A bs ol ut e a n d perce nt e osi n o p hil c o u nts i n peri p heral bl o o d will be c oll ecte d. 
P h ar m ac o ki netic a n d A nti- Dr u g- A nti b o d y E v al u ati o ns 
P har mac o ki netic ( P K) bl o o d sa m ples will be o btai ne d pri or t o t he first d ose o n Da y 1 a n d pre d ose (as 
a p plica ble) o n Da ys 8, 1 5, 2 9, 4 3, 5 7, 7 1, 8 5, 9 9, 1 4 1, a n d 1 6 9 or E T. A d diti o nal P K sa m pl es will be 
c ollecte d i n t he O L E peri o d of t he st u d y. 
Bl o o d (s er u m) will be c ollecte d f or assess me nt of lire nteli m a b A D A usi n g a vali date d assa y met h o d. 
T he A D A bl o o d s a m ples will be o btai ne d pre d ose o n Da ys 1, 4 3, a n d 8 5, as well as o n Da ys 8, 9 9, a n d 
1 6 9, a n d i n t h e e ve nt of a s us p ect e d i m m u n o ge nicit y-relate d A E. 
St atisti c al A n al ysis 
F or all effi cac y vari a bles, t he a nal ysis will be c o m p aris o n of lire nteli ma b S C a n d t he place b o treat me nt 
gr o u ps. T he f oll o wi n g n ull a n d alt er nati ve h y p ot heses f or t he pri mar y e n d p oi nt will be teste d f or 
lire nteli m a b S C gr o u p a n d t he place b o gr o u p: 
H 0: N o treat me nt differe nce bet wee n lire nteli ma b S C a n d pl ace b o 
H 1: T here is a treat m e nt differe nce bet wee n lire nteli m a b S C a n d place b o 
Baseli n e disease se verit y i n d e x [ m o derat e (I G A = 3) a n d se vere (I G A = 4)] a n d pri or bi ol o gic e x perie nce 
( bi ol o gic- naï ve a n d bi ol o gic-e x p ose d) will be t he 2 stratificati o n fact ors f or s u bject ra n d o mizati o n a n d 
will be acc o u nte d f or i n t he st atisti cal m o deli n g f or efficac y. I n a d diti o n, if it is e vi de nt t h at t he pri mar y 
e n d p oi nt is c o nf o u n de d b y st u d y e ntr y c haracteristics [e. g., t he met h o d of I G A a n d/ or E A SI s c ore 
assess m e nt b y A D s pecialist ( defi ne d as t h e PI a n d or S u b-I bei n g eit her a n aller gist, i m m u n ol o gist or 
der m at ol o gist) as c o m pare d t o n o n- A D s pecialist, c ha n ge i n perce nt B S A greater t ha n 2 0 % at t he e n d 
of t he Lea d-i n P hase ( Da y - 1 4 t o Da y - 8) c o m pare d t o t he e n d of t he Baseli n e P h ase ( Da y - 7 t o  
Da y - 1)], t he n t h e pri mar y efficac y a nal ysis will be c o n d ucte d a dj usti n g f or t h e effects of t he 
bac k gr o u n d c haract eristics. 


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St atisti c al A n al ysis c o nt.
T he pri mar y res p o n der e n d p oi nt will be a nal yze d usi n g t he C oc hra n- Ma ntel- Hae nszel test a dj ust e d b y 
baseli ne disease se verit y i n de x [ m o derat e (I G A = 3) a n d se vere (I G A = 4)], pri or bi ol o gi c e x peri e nce 
( bi ol o gic- naï ve a n d bi ol o gic-e x p ose d), a n d c o u ntr y ( U S A a n d Ger m a n y) at Wee k 1 4. T he Ma ntel-
Fleiss ( M F) criteri o n will be perf or me d, a n d if it is n ot m et w hile usi n g t he o pti o n C M H ( M F) i n S A S 
pr oce d ure P R O C F R E Q, a nal yses i n cl u di n g eac h fact or se paratel y i n C M H t est will b e c o n d ucte d. 
S h o ul d ass u m pti o n per t he M F criteri o n n ot be satisfie d, t he c o m paris o n will be base d o n a Fis her’s 
e xact test after c olla psi n g acr oss le vels of t he stratificati o n fact or a n d c o u ntr y. 
F or t he a nal ysis descri be d a b o ve, s u bjects w h o pre m at urel y disc o nti n ue t he ra n d o mize d treat m e nt or 
i nitiate a n y treat me nt a dj ust me nts (e. g., use of pr o hi bite d/resc ue me dicati o n/resc ue treat me nt f or A D 
s y m pt o ms) will be ha n dle d as des cri b e d bel o w: 
 
If a s u bject wit h dra ws fr o m t he st u d y, t his s u bject will be c o u nte d as a n o n-res p o n der f or t h e ti m e 
p oi nts after wit h dra wal. 
 
T o acc o u nt f or t he i m pact of pr o hi bite d/resc ue me dicati o n/resc ue treat me nt f or A D s y m pt o ms o n 
t h e efficac y effect: if resc ue m e dicati o n/resc ue treat me nt f or A D s y m pt o ms is use d, t he s u bject will 
be s pecifie d as a n o n-res p o n der fr o m t he ti m e t he resc ue me dicati o n/resc ue treat me nt is use d. 
 
If t he s u bject has t h e missi n g val ue at Wee k 1 4, it will be c o u nte d as a n o n-res p o n der at Wee k 1 4. 
T he pri mar y efficac y a nal ysis will b e perf or m e d o n t he m o difie d i nte nt-t o-treat ( mI T T) p o p ulati o n, as 
well as per pr ot oc ol ( P P) p o p ulati o n as a s u p p orti n g a nal ysis. I n a d diti o n, f or c o m plete ness p ur p oses, 
res ults i ncl u di n g all s u bjects a n d e xcl u di n g t he s u bjects w h o ha d maj or pr ot o c ol de viati o ns o n t he basis 
of ke y i ncl usi o n a n d e xcl usi o n crit eria defi ni n g t h e p o p ulati o n of i nterest will be prese nte d. T he 
differe nces bet wee n t hese res ults will be n ote d, a n d t he i m pact of s uc h differe nces will be disc usse d i n 
t h e cli nical st u d y re p ort. 
T he bi nar y sec o n dar y efficac y e n d p oi nt will be a n al yze d usi n g t he sa me a p pr oac hes as t h at are use d f or 
t h e a nal ysis of t he pri mar y e n d p oi nt. 
Mi xe d M o del f or Re peate d M eas ures ( M M R M) a nal yses will be perf or me d o n c o nti n u o us e n d p oi nts t o 
miti gate t he i m p act of missi n g data. T his a p pr oac h ass u mes missi n g o bser vati o ns are missi n g at 
ra n d o m a n d b orr o ws i nf or mati o n fr o m s u bjects i n t he s a me treat m e nt gr o u p, ta ki n g i nt o acc o u nt t h e 
missi n g ness of data t hr o u g h t h e c orrel ati o n of t he re peate d meas ure m e nts.  
All c o nti n u o us e n d p oi nts will utilize M M R M after a p pl yi n g t he pri mar y ce ns ori n g r ule, i.e., t he r ul e 
will ce ns or data aft er per ma ne nt st u d y dr u g disc o nti n uati o n or after resc ue t hera p y. T his ce ns ori n g r ule 
is e q ui vale nt t o usi n g all t he data u p t o disc o nti n uati o n or resc ue. 
T he M M R M m o del will i ncl u de fi xe d effects f or baseli ne val ue, diseas e se verit y gr o u p, bi ol o gic- naï ve 
vs bi ol o gic-e x p ose d, c o u ntr y, treat me nt, st u d y wee k, t he treat me nt- b y- wee k i nteracti o n, a n d t he 
baseli ne- b y- wee k i nt eracti o n a n d all o w f or ra n d o m s u bj ect effects. Treat m e nt a n d wee k will eac h be 
fitt e d as cate g orical varia bles. T he m o del will ass u m e u nstr uct ure d c o vari a nce str uct ure. If t he m o del 
wit h u nstr uct ure d c o vari a nce d oes n ot c o n ver ge, t he n ot her c o vari a nce str uct ures will be c o nsi dere d t o 


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m o del t he wit hi n-s u bject err ors. T he Ke n war d- R o gers a p pr oac h f or c o m p uti n g de n o mi nat or de grees of 
free d o m will be use d t o acc o u nt a p pr o priatel y f or p o oli n g of wit hi n-s u bject a n d bet wee n-s u bject 
varia nce esti mates. Efficac y data o n s u bjects w h o pre m at urel y disc o nti n ue t he ra n d o mize d treat me nt or 
i nitiate a n y treat me nt a dj ust me nts (e. g., use of pr o hi bite d/resc ue me dicati o n/resc ue treat me nt f or A D 
s y m pt o ms) will be set t o missi n g at t he desi g nate d ti me p oi nts after wit h dra wal or after t h e start of s uc h 
treat me nt c ha n ges. T he L S M a n d 9 5 % CI f or t he differe nce bet wee n gr o u ps will be esti m at e d usi n g t he 
si m ple c o ntrast at eac h ti me p oi nt. 


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2.
B a c k g r o u n d 
2. 1 
Si glec- 8 a n d Lire nteli m a b  
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 k e 
lecti ns ( Si glecs), is a tra ns me m bra n e cell s urface pr ot ei n wit h restricte d tiss ue distri b uti o n, 
e x press e d s electi vel y o n t h e s urface of mat ure e osi n o p hils a n d mast cells, b ut n ot i n earl y 
prec urs ors of t hese cell p o p ulati o ns. Si glec- 8 c o ntai ns 3 e xtracell ular i m m u n o gl o b uli n-li k e 
d o mai ns, a tra ns m e m bra ne re gi o n, a n d a c yt o plas mic tail c o ntai ni n g 2 t yr osi ne- base d si g nali n g 
m otifs i ncl u di n g a n i m m u n orece pt or t yr osi ne- bas e d i n hi bit or y m otif (I TI M) wit h i n hi bit or y 
f u ncti o n. E n ga ge me nt of Si glec- 8 i n mast cells ca n res ult i n i n hi biti o n of me diat or rele ase, 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 ner, 2 0 0 9). Lire nteli ma b als o s h o ws p ote nt a nti b o d y-
de pe n de nt cell ular c yt ot o xicit y ( A D C C) a gai nst e osi n o p hils i n vi v o a n d i n vitr o. 
2. 2  
O ver vie w of N o ncli nic al St u dies 
Lire nteli ma b is a h u ma ni ze d n o n-f u c 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 g ai nst Si glec- 8, a me m b er of t h e 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 v el y o n t he s urface of m at ure e osi n o p hils a n d mast cells, b ut n ot i n earl y prec urs ors of 
t hese cell p o p ulati o ns. I n bl o o d, bi n di n g of lire nteli m a b t o Si glec- 8 i n d uces A D C C a gai nst 
e osi n o p hils, lea di n g t o ra pi d a n d s ustai ne d d e pleti o n of t hese cells fr o m t he circ ulati o n. I n t h e 
tiss ue, lire nteli ma b i n d uces direct a p o pt osis of e osi n o p hils a n d i n hi biti o n of mast cells.  
Lire nteli ma b has bee n pr o d uce d i n 2 f or m ulati o ns: 1 f or i ntra ve n o us i nf usi o n (lire nteli ma b I V) 
a n d 1 f or s u bc ut a ne o us i njecti o n (lire nteli ma b S C) (see Se cti o n  1 0: St u d y Treat me nt).
Si glec- 8 is n ot e x press e d i n s pecies ot her t h a n h u m a ns a n d hi g h- or d er pri mates, a n d t heref ore, 
2 n o vel m o use m o dels ha ve bee n d e vel o pe d f or i n vi v o testi n g of lire nteli ma b. Lire nteli ma b has 
bee n st u die d i n Si glec- 8 h u m a nize d a n d tra ns ge ni c m o use m o dels a n d wit h h u ma n bl o o d a n d 
tiss ue cells. T he first m o del uses i m m u n o deficie nt mice ca pa ble of ge nerati n g h u ma n i m m u ne 
cells i ncl u di n g mast cells a n d e osi n o p hils w he n e n grafte d wit h h u ma n h e 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 v al uate d 
i n t his m o del. T he s ec o n d r o de nt m o del is a tra ns g e nic m o use li ne t h at e x presses h u ma n 
Si glec- 8. T he e x pressi o n of Si glec- 8 o n t h e cell s urface i n t hese mice is restricte d t o e osi n o p hils, 
mast cells, a n d bas o p hils, a patter n of s urface e x pressi o n e q ui vale nt t o t hat i n h u ma ns. 
A nti- Si glec- 8 a nti b o dies ca n pre v e nt I g E- m e diate d a na p h yla xis i n t his tra ns ge ni c m o use li ne, 
i n dicati n g t h at Si glec- 8 is p har mac ol o gicall y acti v e i n t he m o del. T he a bilit y of lire nteli m a b t o 
affect mast cells a n d e osi n o p hils has bee n e val u ate d i n t his m o del. 


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Lire nteli ma b i n hi bits I g E- me diate d mast cell de gra n ulati o n a n d rel ease of t he ne wl y f or me d 
me diat or pr ost a gla n di n D 2 i n vitr o wit h o ut affecti n g mast cell via bilit y. I n peri p heral bl o o d 
pre parati o ns fr o m n or mal h u ma n d o n ors, lire nteli ma b s h o ws selecti ve de pl eti o n of e osi n o p hils.
I m p ort a ntl y, i n a w h ole- bl o o d c yt o ki ne-release ass a y usi n g i m m o bilize d lire nteli ma b t o e n ha nc e 
t he p ote ntial f or a nti b o d y cr ossli n ki n g, lire nteli ma b di d n ot lea d t o d ose- de pe n de nt release of 
pr o-i nfla m mat or y c yt o ki nes. 
T o e val 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 h at selecti vel y e x presses h u ma n Si glec- 8 
o n t he s urface of m o use mast cells, e osi n o p hils, a n d bas o p hils. I n si n gle- d ose a n d re peat- d os e 
st u dies i n Si glec- 8 tra ns ge nic mice, lire nteli ma b d e m o nstrate d selecti ve de pleti o n of perit o neal 
mast cells a n d circ ul ati 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 t he 1- m o nt h a n d 6- m o nt h G o o d La b orat or y Practice ( G L P) t o xicit y a n d t o xic o ki neti c st u dies, 
lire nteli ma b I V w as w ell 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 h u ma ns. Lire nteli ma b 
s h o we d s ustai ne d s yste mic e x p os ure i n Si glec- 8 tra ns ge nic mice wit h a n e xte n de d ter mi nal 
half-life esti m ate d as 2 7 2 h o urs or 3 3 7 h o urs f oll o wi n g si n gle I V a d mi nistrati o n of 5 0 m g/ k g or 
1 0 0 m g/ k g, res pecti vel y. T here w as n o e vi de n ce of a nti- dr u g a nti b o dies ( A D A) i n eit h er st u d y. 
Decr eases i n e osi n o p hil c o u nts i n b ot h se xes were o bser ve d, w hic h refl ect t he e x pecte d 
p har mac ol o g y of lire nteli ma b. 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 ntra ve n o us a d mi nistrati o n of lire nteli ma b t o tra ns ge nic mice w as 1 0 0 m g/ k g. 
A G L P t o xic ol o g y st u d y was c o n d ucte d t o c haract erize t he l o cal t olera n ce a n d bi o a vaila bilit y of 
lire nteli ma b S C i n tra ns g e nic mice t o s u p p ort h u m a n cli nical st u dies. T he d ose, 6 0 m g/ k g, was 
selecte d t o re pres e nt a d ose le vel 6-f ol d hi g her t ha n t he hi g hest h u ma n d ose le vel ( 1 0 m g/ k g), 
t o i d e ntif y a N O A E L/ n o o bser v e d effect le vel ( N O E L) a n d w as re prese nt ati ve of t he I V 
lire nteli ma b d oses pre vi o usl y st u die d ( 5 0 m g/ k g a n d 1 0 0 m g/ k g). T here w ere n o 
lire nteli ma b-relat e d cli nical o bser v ati o ns f oll o wi n g S C or I V a d mi nistrati o n, a n d t here w ere 
n o lire nteli ma b-relat e d s ki n reacti o ns n ote d f oll o wi n g S C or I V a d mi nistrati o n. 
A G L P st u d y of lire nteli ma b S C was c o n d ucte d usi n g C 5 7 Bl/ 6 m ale bree d er mice a n d F 0 
ge nerati o n Si glec- 8 tr a ns ge nic fe mal e mice t o e val u ate t he effects of 6 0 m g/ k g lire nteli ma b S C 
o n fertilit y, de vel o p me nt, a n d p eri n atal/ p ost n atal re pr o d ucti o n, i ncl u di n g p ost natal 
be ha vi or/f u ncti o n. O bser vati o ns were c o nti n ue d t hr o u g h s e x ual mat urit y of t he F 1 g e nerati o n 
mice. T here w ere n o lire nteli ma b-relate d effects o n fertilit y, de vel o p me nt, or peri natal/ p ost natal 
re pr o d ucti o n, or o n t he p ost natal be ha vi oral assess me nts. Base d o n t hese res ults, t h e N O A E L of 
lire nteli ma b S C was c o nsi d ere d t o be 6 0 m g/ k g. 


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O ver vie w of Cli ni c al St u dies
Lire nteli ma b I V, a d mi nistere d e v er y 4 w ee ks, h as bee n pre vi o usl y teste d i n o ver 7 0 0 healt h y 
v ol u nteers a n d patie nts wit h i n d ole nt s yste mic mast oc yt osis (I S M), c hr o nic urticaria ( C U), 
se vere aller gi c c o nj u ncti vitis ( A C), mast cell g astritis, a n d e osi n o p hilic gastritis ( E G) a n d/ or 
e osi n o p hilic d u o de nitis ( E o D). M ulti ple d oses of 3 m g/ k g ha ve bee n gi v e n t o patie nts wit h I S M, 
C U, A C, mast cell gastritis, a n d E G a n d/ or E o D. 
I n g e neral, lire nteli ma b I V has bee n w ell t olerate d. T he m ost c o m m o n treat m e nt-e mer g e nt 
a d verse e ve nts ( T E A E) o bser v e d w ere i nf usi o n-relate d reacti o ns (I R R). T he I R R were m ostl y 
mil d t o m o derate, a n d occ urre d m ost ofte n d uri n g t he first i nf usi o n. I R R t h at were d ee me d m ore 
seri o us t y picall y res ol ve d wit hi n 2 4 h o urs, a n d a d diti o nal c ortic oster oi ds a n d/ or a nti hista mi nes 
were us e d i n cases w he n sl o wi n g t he rate of i nf usi o n a n d a d diti o nal s u p p orti v e care al o ne di d n ot 
res ol v e t h e iss ue. C o m m o n s y m pt o ms of I R R were hea d ac he, n a usea, s w eati n g, fl us hi n g, a n d 
re d n ess. M ost I R R t h at occ urre d d uri n g t h e 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 h e i nf usi o n, wit h mi ni mal i nter ve nti o n. I n s u bjects wit h I S M, C U, se vere A C, 
a n d E G/ E o D, fe wer a d verse e ve nts ( A E) i n cl u di n g I R R were re p orte d d uri n g t h e sec 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 ris k of I R R has bee n s u bsta nti all y 
re d u ce d b y a d mi nistrati o n of a si n gle d ose of oral c ortic oster oi d (e. g., pre d nis o ne 6 0 m g) gi ve n 
orall y 1 2 t o 2 4 h o urs pri or t o t he first d ose of lire nt eli ma b I V.  
St u d y A K 0 0 2- 0 1 7 e val uate d t he P K a n d P D of lire nteli ma b I V a n d S C i n healt h y v ol u nteers. 
S u bjects recei v e d 0. 3, 1, 3, or 5 m g/ k g or a fi xe d d ose of 3 0 0 m g or 4 5 0 m g lire nteli ma b S C, or 
1 m g/ k g or 3 m g/ k g lire nteli ma b I V. 
I n eac h of t h e S C c o h orts, 8 s u bjects w ere ra n d o mize d t o lire nteli m a b ( 6 per gr o u p) or pla ce b o 
( 2 per gr o u p) i n a d o u ble- bli n d ma n ner; 1 2 s u bjects recei v e d lire nteli ma b I V ( 6 s u bjects per 
gr o u p) i n a n o pe n-la bel m a n ner.  
T he st u d y s h o we d t h at t h e P D effect ( de pl eti o n of bl o o d e osi n o p hils) occ urre d wit hi n 1 h o ur of 
d osi n g a n d laste d f or at l east 1 m o nt h at I V a n d S C d oses of 1 m g/ k g a n d f or 3 m o nt hs at all 
hi g her I V a n d S C d oses. T he S C i njecti o ns w ere well t olerate d, a n d n o i nj ecti o n sit e reacti o ns or 
ge neral i nje cti o n reacti o ns were n ote d at a n y d ose de m o nstrati n g s uita bilit y f or f urt her 
e val uati o n. 
I n t he A K 0 0 2- 0 0 5 st u d y i n patie nts wit h se vere A C, lire nteli ma b de m o nstrate d cli nical acti vit y 
i n relie vi n g t he si g ns a n d s y m pt o ms of se vere A C acr oss all m eas ure d d o m ai ns. T he st u d y 
s h o we d a 6 1 % i m pr o v e me nt i n patie nt-re p ort e d oc ular s y m pt o ms (t otal aller gic c o nj u ncti vitis 
s y m pt o ms [ A C S]) a n d 7 9 % of s u bjects were d ee me d res p o n ders at 2 wee ks f oll o wi n g t h e fi nal 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 3 4 of 1 3 5 
C o nfi d e nti al  
lire nteli ma b d ose c o m p are d t o baseli n e. I n v esti g at or-assesse d o c ular si g ns a n d s y m pt o ms (t otal 
O S S) als o i m pr o ve d b y 5 3 %, a n d 8 3 % of s u bjects were d ee me d res p o n ders at t he fi nal d ose ti me 
p oi nt c o m pare d t o baseli ne. A d diti o nall y, s y m pt o m b ur de n w as ass esse d acr oss m ulti ple at o pic 
c o m or bi dities, a n d s y m pt o m s e verit y decrease d s u bsta ntiall y acr oss all c o n diti o ns assesse d, 
i ncl u di n g i n at o pic der matitis ( A D), ast h ma, a n d r hi nitis. 
T he lac k of tr eat m e nt-rel ate d a d verse e ve nts ( A E) be y o n d I R R i n t he I V st u dies c o m bi ne d wit h 
t he cli nical acti vit y o bser ve d i n treati n g m ulti ple aller gic c o n diti o ns a n d t he ret ur n of si g ns a n d 
s y m pt o ms off treat m e nt ma ke lire nteli ma b a p ote ntiall y pr o misi n g ca n di date f or m ulti ple 
e osi n o p hil a n d mast cell- dri v e n i nfla m mat or y diseases, i ncl u di n g A D. 
2. 4  
At o pi c D er m atitis a n d R ati o n ale f or t he St u d y
At o pic der matitis is a c hr o nic pr uritic i nfla m mat or y der matitis t hat affects a p pr o xi m atel y 
1 6. 5 milli o n ( 7. 3 %) a d ults i n t he U S, of w hic h ar o u n d 6. 6 milli o n ( 4 0 %) ha ve m o derate-t o-
se vere disease. T h e pat h o ge nesis of A D is c o m ple x a n d i n v ol ves a b n or malities i n s ki n barrier 
f u ncti o n, altere d s ki n fl ora, a n d i m m u ne d ysre g ulati o n ( F u xe nc h, 2 0 1 9). T h ere is i ncrease d 
e x pressi o n of T h 2 a n d T h 2 2 c yt o ki nes li ke I L- 4, I L- 1 3, I L- 3 1, a n d I L- 2 2. M ast cell n u m bers are 
ele vate d i n t he s ki n of A D patie nts. T hese cells, b y virt u e of pr o d uci n g pr urit o ge nic me diat ors 
li k e hist a mi n e, tr y ptase a n d I L- 3 1, mi g ht c o ntri b ute t o A D s y m pt o ms. I n a d diti o n, mast cells 
ma y c o ntri b ute t o ne ur o g e nic i nfla m mati o n b y i nteracti n g wit h se ns or y n er ves. I n a d diti o n t o 
mast cells, e osi n o p hils ma y be ele v ate d i n patie nts wit h A D. It has bee n d e m o nstrate d t hat 
e osi n o p hils ta ke n fr o m A D bi o psies are acti v ate d a n d s h o w d ela y e d pr o gra m me d cell deat h. 
Ta ke n t o get her, t hese fi n di n gs s u g gest t hat acti vati o n a n d de gra n ulati o n of mast cells a n d 
e osi n o p hils m a y be a maj or c o m p o ne nt i n t h e pat h o ge nesis of A D a n d ma y re pres e nt s uita ble 
tar gets f or t hera pe utic i nt er v e nti o n. 
At o pic der matitis patie nts t y picall y e x perie n ce dr y s ki n a n d i nte nse pr urit us, w hic h ca n le a d t o 
de vel o p me nt of er yt h e mat o us pa p ules wit h e x u dati o n, cr usti n g, a n d e xc oriati o n. A rece nt st u d y 
of a d ults wit h m o derate-t o-se vere A D f o u n d t h at 7 0. 5 % re p orte d se vere, u n beara bl e itc h i n t he 
past 2 wee ks, 8 5. 8 % re p orte d dail y itc h, a n d 6 2. 8 % re p orte d itc hi n g at least 1 2 h o urs per da y. 
C hr o nicall y, t his ofte n lea ds t o s ki n t hic ke ni n g a n d lic he nificati o n, m ost c o m m o nl y i n s ki n 
fle x ures.  
At o pic der matitis ma y i n v ol ve t he face, n ec k, tr u n k, a n d e xtre mities. At o pi c der m atitis f oll o ws 
a c hr o nic rela psi n g c o urse a n d ca n be c o m plicate d b y de vel o p me nt of b acterial a n d viral s ki n 
i nfecti o ns. Patie nts wit h A D als o ha ve a n i ncrease d ris k of aller gic r hi nitis, ast h ma, f o o d 
aller gi es, a n d o c ular c o n diti o ns li ke at o pic kerat o c o nj u ncti vitis ( A K C) a n d v er nal c o nj u ncti vitis 
( V K C). 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 3 5 of 1 3 5 
C o nfi d e nti al  
T he mai n g oals of A D treat me nt are t o mai ntai n a d e q uate s ki n h y drati o n, re d u ce pr urit us a n d 
pre ve nt e x acer bati o ns. W hile oral a nti- hista mi nic a ge nts ma y hel p re d uce pr urit us, t o pical a ge nts 
are t h e m ai nsta y of treat m e nt. T hese i ncl u de m oist urizi n g/ e m ollie nt pre parati o ns, w hic h pr ote ct 
t he s ki n barrier a n d pre v e nt water l oss. Al o n g wit h m oist urizi n g a ge nts, t o pical a nti-
i nfla m mat or y a ge nts s uc h as c ortic oster oi ds a n d calci ne uri n i n hi bit ors (e. g., tacr oli m us a n d 
pi mecr oli m us) are us e d f or mil d-t o- m o derate disease as sec o n d li ne o pti o ns. Crisa b or ole, a 
t o pical p h os p h o diesteras e 4 ( P D E 4) i n hi bit or, was a p pr o ve d b y t he F D A i n Dece m b er 2 0 1 6, 
a n d is use d f or treat me nt of mil d-t o- m o derate A D. W hile t o pical a ge nts ca n be effecti ve i n mil d-
t o- m o derate disease, t here are l o n g ter m safet y c o ncer ns. T o pical ster oi ds ca n ca use s ki n atr o p h y 
a n d p ossi ble a dre n al s u p pressi o n d ue t o s yste mic a bs or pti o n. Tacr oli m us a n d pi mecr oli m us carr y 
a p ote nti al ris k of s ki n ca ncer, w hic h h as res ulte d i n a blac k b o x w ar ni n g b y t he F D A.  
T he ma na ge me nt of m o d erate-t o-se vere disease is m ore diffic ult. Patie nts ca n be treate d wit h 
p h ot ot h era p y ( 3 ti mes per wee k), w hic h is c u m bers o me, e x p e nsi v e, a n d m a y i ncreas e t he ris k of 
de vel o pi n g s ki n ca ncer. Oral c ortic oster oi ds are o ccasi o nall y use d b ut are li mite d b y si de effects 
i ncl u di n g i n crease d ris k of dia betes, h y perte nsi o n, a dre nal s u p pressi o n, a n d e ye diseas es li ke 
gla uc o ma a n d cataracts. A n oral cal ci ne uri n i n hi bit or (c ycl os p ori n) ca n be use d b ut re q uires 
fre q ue nt m o nit ori n g of dr u g le vels a n d carries ris ks of h y perte nsi o n, ne p hr ot o xicit y, 
h y pertric h osis, a n d g u m h y per plasia. Als o, l o n g-t er m use of ster oi ds a n d c ycl os p ori n lea ds t o 
i m m u n os u p pressi o n a n d i ncreas e d ris k of i nfecti o ns.  
I n M arc h 2 0 1 7, t h e F D A a p pr o ve d d u pil u ma b f or t h e treat m e nt of a d ult patie nts wit h m o derate-
t o-se vere A D n ot a de q uatel y c o ntr olle d wit h t o pical prescri pti o n t hera pies or w he n t h ose 
t hera pies are n ot a d visa bl e. D u pil u ma b is a f ull y h u ma n m o n ocl o nal a nti b o d y t h at bi n ds t o t he 
al p ha s u b u nit of t he I L- 4 rece pt or a n d i n hi bits si g nali n g of I L- 4 a n d I L- 1 3, alteri n g T-cell 
me diate d i m m u ne res p o nse, w hic h is belie ve d t o pla y a r ole i n A D. T h e l o n g-ter m ( 5 2 wee k) 
safet y a n d efficac y of d u pil u ma b was e val uate d i n a ra n d o mi ze d, d o u bl e- bli n d, place b o-
c o ntr olle d st u d y. C o nc o mita nt use of t o pical c ortic oster oi ds (a n d t o pical calci ne uri n i n hi bit ors, if 
i n dicate d) was all o we d. 
I n t he d u pil u ma b st u d y at Wee k 5 2, m ore patie nts i n t he d u pil u ma b-treate d gr o u p ac hie ve d t he 
I n v esti gat or Gl o bal Assess me nt (I G A) a n d Ecz e ma Area a n d Se verit y I n de x ( E A SI)- 7 5 
e n d p oi nts t ha n t he place b o-treate d gr o u p (a p pr o xi matel y 4 0 % vers us 1 3 % a n d 6 5 % vers us 2 2 %, 
res pecti vel y). H o we v er, t he d u pil u ma b-treat e d patie nts ha d a 2-f ol d hi g her i nci de nce of e ye 
dis or ders i n cl u di n g n o n-i nfecti o us c o nj u ncti vitis. T here c o nti n ues t o be a s u bsta ntial nee d f or 
ne w a n d better treat me nts f or m o derat e-t o-se v ere A D. B y re d uci n g e osi n o p hil n u m bers a n d 
bl oc ki n g mast cell acti v ati o n, lire nteli ma b ma y be usef ul i n t he treat m e nt of p atie nts wit h A D. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 3 6 of 1 3 5 
C o nfi d e nti al  
T his pr o of- of-c o nce pt st u d y will e val uate t he safet y, t olera bilit y, a n d P D of re peat d os es of 
lire nteli ma b S C i n pati e nts wit h m o derate-t o-se v ere A D a n d pr o vi de e vi de n ce f or effi cac y as 
assess e d b y s y m pt o mat ol o g y a n d s ki n e xa mi n ati o n. I n t his st u d y, s u bjects wit h m o derate-
t o-se vere dis ease, w hic h is defi ne d usi n g t he f oll o wi n g crit eria, will be i n cl u de d: 
C hr o nic A D t h at h as bee n dia g n ose d a n d prese nt f or at least 3 years at t he ti me of 
scree ni n g.  
 
S u bjects w h o ha ve faile d t o res p o n d t o me dicate d t o pical treat me nts (c ortic oster oi ds, 
calci ne uri n i n hi bit ors a n d/ or crisa b or ole) or w h e n t h ese treat me nts are c o ntrai n dicat e d or 
n ot me dicall y a d visa ble f or t h e s u bject.  
 
b o d y s urfa
 
T hese well-esta blis he d meas ures will o bjecti v el y defi ne t h e se v erit y of t h e dis ease at t h e ti m e of 
e ntr y i nt o t he st u d y. 
3.
R ati o n ale f or D os e Sel ecti o n 
A d osi n g re gi me n of 3 0 0 m g lire nteli ma b S C a d mi nistere d e ver y 2 w ee ks f or 7 d oses is 
pr o p ose d. T his re gi m e n is base d o n P K m o deli n g f or St u d y A K 0 0 2- 0 1 7, c o m p ari n g d osi n g 
re gi m e ns f or t he I V i nf usi o n d oses vs. t he S C i njecti o n d oses a d mi nistere d e ver y 2 8 da ys. T hese 
si m ulati o ns s h o we d t h at a d ose of 3 0 0 m g lire nteli ma b S C pr o vi d e d a s u bsta ntiall y l o wer C ma x  
a n d sli g htl y l o wer 1- m o nt h tr o u g h le vel t h a n 3 m g/ k g lire nteli m a b I V.  
Disc ussi o n wit h e x perts p artici pati n g i n der mat ol o gic trials wit h bi ol o gics a n d re p orts of e xter nal 
data fr o m ot her c o m p o u n ds tar geti n g A D s u p p ort t he use of hi g her or m ore fre q u e nt d osi n g t ha n 
i n ot h er aller gic diseases. Se veral st u dies ha ve re p orte d t hat hi g her or m ore fre q ue nt d osi n g is 
re q uire d f or t y pe II i m m u ne c o n diti o ns, f or e xa m pl e ast h ma, c o m p are d wit h A D. D ose-res p o nse 
relati o ns hi ps a n d res ults acr oss m ulti ple e n d p oi nts s h o w tre n ds t o war d i m pr o ve d efficac y wit h 
i ncreasi n g d ose a n d d urati o n a n d s u g gest t h at f urt h er i n creases i n d ose or treat me nt d urati o n 
mi g ht i m pr o ve efficac y ( Castr o, 2 0 1 8; C orre n, 2 0 1 7; Si m ps o n, 2 0 1 8; Si m ps o n, 2 0 1 9; Si m ps o n, 
2 0 2 0; Sil ver ber g, 2 0 2 0; W olle n ber g, 2 0 1 9) . C o ns e q ue ntl y, i ncreasi n g t he d ose fre q u e nc y of t h e 
3 0 0 m g d ose fr o m e ver y 4 wee ks t o e ver y 2 wee ks is pr o p ose d f or t h e A K 0 0 2- 0 1 8 st u d y.  
Si m ulati o ns usi n g A K 0 0 2- 0 1 7 st u d y data i n dicate t h at a fi xe d d ose of lire nteli ma b S C 3 0 0 m g 
e ver y 2 w ee ks is e x p ecte d t o pr o vi de great er e x p os ure t h a n t he 3 0 0 m g d os e a d mi nistere d 
m o nt hl y wit h o ut a n i ncrease d C ma x  c o m pare d wit h t he 3 m g/ k g I V d os e. T his d ose a n d fre q u e nc y 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 3 7 of 1 3 5 
C o nfi d e nti al  
of a d mi nistrati o n will res ult i n hi g her stea d y state le vels a n d is s u p p orte d b y a n e xc elle nt safet y 
a n d t olera bilit y pr ofile of lire nteli ma b i n patie nts wit h ot h er e osi n o p hilic a n d mast cell diseases. 
T he c o nce ntrati o n of lire nteli ma b S C of 1 5 0 m g/ m L is c o nsiste nt wit h a n i njecti o n v ol u me of 
2 m L f or t he 3 0 0 m g d ose, w hic h was well t olerat e d wit h o ut i njecti o n site reacti o ns i n St u d y 
A K 0 0 2- 0 1 7. W h e n pr o of of c o nce pt is esta blis he d, ot h er lire nteli ma b S C d oses a n d sc he d ul es 
ma y be e x pl ore d.
4.
St u d y O bjecti v es a n d E n d p oi nts
4. 1  
Pri m ar y O bjecti ve a n d E n d p oi nt 
T he pri mar y o bje cti v e of t he st u d y will be t o c haracterize t h e efficac y of lire nt eli m a b S C i n a d ult 
s u bjects wit h A D as assesse d b y t he differe nc e i n t h e pr o p orti o n of s u bjects w h o ac hie ve 
E A SI- 7 5 at Wee k 1 4. 
4. 2  
Sec o n d ar y O bjecti ves a n d E n d p oi nts 
T o f urt her c haracterize t h e effi cac y of lire nteli ma b S C i n a d ult s u bjects wit h A D as meas ure d b y 
t he f oll o wi n g: 
 
% C ha n ge i n E A SI fr o m baseli ne t o Wee k 1 4. 
 
Pr o p orti o n of s u bjects wit h I G A of 0 or 1 a n d a 2- p oi nt i m pr o ve me nt at Wee k 1 4 
vs baseli ne. 
4. 3  
E x pl or at or y O bjecti ves a n d E n d p oi nts 
T he e x pl orat or y o bj ecti v es of t he st u d y are t o better c haracteriz e t h e ti mi n g a n d nat ure of t he 
cli nical res p o nse t o lire nt eli m a b S C i n a d ult s u bjects as meas ure b y t h e f oll o wi n g e x pl orat or y 
effic ac y e n d p oi nts: 
 
C ha n ge i n 
 of 
slee p l oss at Wee k 1 4. 
 
Ti me t o o nset of res p o ns e o n t he 
, w here 
res p o nse is defi n e d as i m pr o ve me nt (at least a  
 re d ucti o n fr o m baseli n e) of wee kl y 
a vera g e of d ail y  
 d uri n g t h e 1 4- wee k treat me nt peri o d. T he a n al ysis will be base d o n 
 
C ha n ge fr o m baseli ne t o Wee k 1 4 i n  
 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 3 8 of 1 3 5 
C o nfi d e nti al  
 
P D of lire nteli ma b S C i n s u bjects wit h A D as meas ure d b y c ha n g es fr o m b aseli ne i n 
. 
 
Ot her i n dices of effic ac y of lire nteli ma b S C i n s u bjects wit h A D. C h a n ges i n si g ns a n d 
s y m pt o ms (c o m p are d t o baseli ne) bet w ee n lire nt eli ma b a n d place b o will b e meas ure d b y:
 C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
 
 C ha n ge i n  
 fr o m baseli ne t o Wee k 1 4
 Pr o p orti o n of s u bjects w h o ac hie ve  
 
 Pr o p orti o n of s u bjects w h o ac hie ve  
 
 C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
  
 C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
  
 C ha n ge fr o m baseli ne o v er ti me i n 
 
4. 4  
S afet y O bjecti v es 
T o e val uate t he s afet y a n d t olera bilit y of lire nteli ma b S C i n s u bjects wit h A D 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 E, 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 E, a n d ot her s afet y 
para m eters.
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 E, 
i ncl u di n g a n y reacti o ns t o t h e S C i njecti o n. All T E A E will be c ollecte d fr o m t he st art of st u d y 
dr u g a d mi nistrati o n t hr o u g h Da y 1 6 9 ( ± 5 da ys) or Earl y T er mi n ati o n ( E T) d uri n g t he d o u ble-
bli n d peri o d of t h e st u d y. 
Se verit y 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 Ter mi n ol o g y 
Criteria f or A d v erse E v e nts ( C T C A E) ta bles a n d t o xicit y gra di n g scale ( versi o n 5 or m ost c urre nt 
versi o n). All A E will be assi g ne d a se verit y gra de a n d will be assesse d t o d eter mi ne w het h er 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 u ati o ns i ncl u de cli nical la b orat or y tests c o m prisi n g a nti- dr u g a nti b o d y 
( A D A) t o lire nt eli ma b S C, c o m plete bl o o d c o u nts, c he mistries, a n d uri nal yses; p h ysical e xa ms; 
a n d vital si g n meas ure m e nts. 
T he Me dical M o nit or will re vie w bli n de d safet y d ata t hr o u g h o ut t he st u d y. Certai n safet y d ata 
( p ost-treat m e nt cell differe nti als) c ollecte d d uri n g t he d o u ble- bli n d peri o d of t he st u d y will n ot 
be pr o vi de d t o st u d y sites or t o t he S p o ns or as it ma y ca use bi as. T he desi g n ate d Safet y M o nit or 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 3 9 of 1 3 5 
C o nfi d e nti al  
will re vie w bli n de d safet y data as well as p ost-treat me nt cell c o u nts a n d will escalate t o t h e 
Me dical M o nit or, as nee de d, i n a ma n ner t h at d oes n ot ca us e bias.  
A n i n de pe n de nt D ata
M o nit ori n g C o m mittee (i D M C) has bee n c o n v e ne d a n d will meet i n 
acc or d a nce wit h t he i D M C c harter.
5.
St u d y Desi g n
5. 1 
St u d y O ver vie w
T his P h ase 2, pr o of- of-c o n ce pt, ra n d o mi ze d, d o u ble- bli n d, place b o-c o ntr oll e d st u d y will 
i n vesti gate t he effi cac y a n d safet y of lire nt eli m a b S C i n a d ult s u bjects wit h m o derate-t o-s e vere 
A D i na de q uatel y c o ntr olle d b y t o pical treat m e nts. A p pr o xi m atel y 1 3 0 s u bje cts will be e nr olle d 
i n u p t o 7 0 sites i n t he U S a n d Ger ma n y a n d will be ra n d o mize d 1: 1 t o recei ve eit her 
7 S C i njecti o ns of place b o or lire nteli ma b a n d t he n f oll o we d f or 1 2 w ee ks after t h e l ast d ose. 
S u bjects will be gi ve n t he o pti o n t o e nr oll i nt o a n o pe n-la bel e xt e nsi o n ( O L E) peri o d of t he 
st u d y, after c o m pleti n g t he Da y 9 9 visit of t he d o u ble- bli n d peri o d. S u bjects c h o osi n g n ot t o 
e nter t h e O L E p eri o d will c o nti n ue t o be f oll o we d i n t he d o u ble- bli n d peri o d of t he st u d y f or 
1 2 wee ks after t he last d ose. 
Base d o n t he fee d bac k fr o m at o pic der matitis e x p erts a n d c o m plete d feasi bilit y assess me nts, it is 
e x pecte d t h at eac h site will be a ble t o scree n t hree s u bjects a n d e nr oll t w o of t he m i n t he d urati o n 
of t he e nr oll m e nt p eri o d. E nr oll me nt is c o nsi dere d t o be c o m petiti ve. T o e ns ure t he e nr oll me nt 
g oal is ac hi e ve d i n a ti mel y ma n ner, u p t o 7 0 sites (a p pr o xi matel y 5 5 i n t he U S a n d
a p pr o xi matel y 1 5 i n Ger ma n y) will be i niti ate d. If st u d y e nr oll m e nt rate ca n be ac hie v e d wit h 
fe wer sit es i n or der t o meet t he st u d y ti meli ne, t he n fe wer sites ma y be nee de d. 
S u bjects will be c o nse nte d a n d scree ne d, a n d t h ose w h o meet eli gi bilit y crit eria ca n b e e nr olle d 
i n t h e st u d y. S u bjects 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 de ntificati o n n u m ber a n d 
rescree ne d o n ce. S u bjects rescree ne d wit hi n 3 0 da ys of si g ni n g t he i nitial i nf or me d c o ns e nt f or m 
(I C F) will n ot nee d t o si g n a ne w I C F if t here h a ve bee n n o c ha n ges t o t he I C F. 
S u bjects will be scree n e d f or a p pr o xi matel y 2 w ee ks (- 1 4 da ys) pri or t o d ose a d mi nistrati o n. 
D uri n g scre e ni n g a n d t hr o u g h vari o us ti me p oi nts d uri n g t h e st u d y, t he E A SI, I G A,  
 
 assess me nts will b e c o m plete d. A d diti o nal q uesti o ns will be as ke d 
a b o ut s y m pt o ms relate d t o ast h ma, aller gic r hi nitis, a n d aller gic c o nj u ncti vitis t hat s u bjects wit h 
t he at o pic c o n diti o n(s) m a y ha ve o n Da y 1, Da y 9 9, a n d O L E Da y 9 9 ( At o pic C o n diti o ns 
Q uesti o n naire). T o e ns ure t h ere is s uffi cie nt patie nt-re p orte d o utc o m e ( P R O) d ata at b aseli ne, a 


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s u bject s h o ul d c o m plete at least f o ur dail y P R O q u esti o n naires per wee k f or a mi ni m u m peri o d 
of t he se ve n d a ys pri or t o Da y 1. 
Certai n me dicati o ns are pr o hi bite d d uri n g t he st u d y. Use of s yste mic a n d/ or t o pical 
c ortic oster oi ds, calci ne uri n i n hi bit ors, J A K i n hi bit ors, t o pical P D E 4 i n hi bit ors (crisa b or ol e), 
d u pil u ma b, or tral o ki n u ma b are pr o hi bit e d d uri n g t h e st u d y. S u bjects w h o are o n a n y t o pical 
c ortic oster oi ds, t o pical calci ne uri n i n hi bit ors, t o pical J A K i n hi bit ors, or P D E 4 i n hi bit ors at t he 
ti m e of scree ni n g m ust disc o nti n ue t h ese at t he first scree ni n g visit. Bi ol o gics or m e dicati o ns t hat 
ma y i nterfere wit h t he st u d y safet y or effic ac y ass ess me nts s uc h as s yste mic 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 or bi ol o gics a n d s yste mic c ortic oster oi ds m ust b e dis c o nti n ue d 
pri or t o t he first scree ni n g visit (see Secti o n  8. 5 E xcl usi o n Criteria) a n d are pr o hi bite d 
t hr o u g h o ut t he st u d y. 
D uri n g t he last 7 da ys pri or t o Da y 1 (t he first da y of st u d y dr u g d osi n g), t he s u bject m ust ha ve 
use d, at least t wice d ail y, o nl y n o n- me dicate d t o pi cal t h era p y (i.e., e m olli e nt) wit h o ut ot her 
acti v e i n gre die nts i n dicat e d t o treat A D or ot h er a d diti ves w hic h c o ul d affect A D (e. g., 
h yal ur o nic aci d, urea, cera mi de, or fila g gri n de gra dati o n pr o d ucts). If a s u bject is n ot usi n g a n y 
e m ollie nt at t he ti m e of scree ni n g, a s uita ble n o n- me dicate d, n o n- prescri pti o n e m olli e nt will be 
rec o m me n d e d b y t h e I n v esti g at or. 
Eli gi ble s u bjects w h o m eet selecti o n criteria at scree ni n g a n d at b aseli ne will recei ve t he first 
d ose of lire nteli ma b S C or place b o S C o n Da y 1, f oll o we d b y 6 a d diti o nal d oses o n Da ys, 1 5, 2 9, 
4 3, 5 7, 7 1, a n d 8 5. 
S u bjects will be gi ve n t he o pti o n of e nteri n g a n O L E peri o d of t he st u d y after c o m pleti n g t he 
Da y 9 9 visit of t he d o u ble- bli n d peri o d of t h e st u d y, c o nti n ge nt o n meeti n g defi ne d st u d y 
selecti o n criteria. S u bjects n ot e nteri n g t he O L E p eri o d will be f oll o we d f or 1 2 wee ks after t h e 
last d ose i n t he d o u ble- bli n d peri o d.  
T he pri mar y e n d p oi nt will be assesse d at Wee k 1 4, i.e., 2 wee ks f oll o wi n g t he last d ose i n t he 
d o u ble- bli n d peri o d of t h e st u d y. 
Ra n d o mizati o n will b e stratifie d b ase d o n I G A 3 vs. 4 a n d o n bi ol o gic st at us, naï ve vs. e x p ose d. 
A p pr o xi matel y 4 0 % of t he st u d y p o p ulati o n will be s u bjects wit h a n I G A of 4. 
Fres h bi o psies of l esi o nal a n d n o n-lesi o nal s ki n ma y be c ollecte d fr o m p atie nts pre d ose a n d p ost-
d ose at select e d U S sites. Pr o vi di n g bi o psies is o pti o nal, a n d s u bjects will si g n a se parate c o ns e nt 
f or m f or bi o ps y c ollecti o n. 


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T he st u d y is desi g ne d as f oll o ws: 
A scree ni n g peri o d of a p pr o xi matel y 1 4 da ys wit h baseli n e e val u ati o ns f or st u d y eli gi bilit y. 
 
D uri n g t he scree ni n g peri o d, t h e E A SI, 
 will be deter mi n e d, a n d a 
baseli n e will be esta blis h e d.
 
If s u bjects meet eli gi bilit y criteria, t he I nteracti v e Res p o nse T ec h n ol o g y (I R T) s yste m will 
assi g n s u bjects 1: 1 t o recei ve 7 d oses of 3 0 0 m g lire nteli m a b S C or place b o S C. S u bjects 
will b e stratifie d b ase d o n bi ol o gic- naï ve vs bi ol o gic-e x p ose d stat us a n d I G A sc ore at 
baseli n e. 
 
Eli gi ble s u bjects will recei ve t he first d ose of lire nteli ma b S C or i d e nti cal place b o o n 
Da y 1. If t h e st u d y dr u g is w ell t olerate d ( n o st o p pi n g r ules bei n g met), s u bjects will recei v e 
a d diti o nal d oses of lire nt eli ma b S C or place b o S C o n Da ys 1 5 ( D ose 2), 2 9 ( D ose 3), 
4 3 ( D ose 4), 5 7 ( D ose 5), 7 1 ( D ose 6), a n d 8 5 ( D ose 7). 
 
S u bjects will be gi ve n a n o pti o n of e nteri n g t he O L E peri o d t o recei v e 7 a d diti o nal d oses of 
o pe n-la bel st u d y dr u g. 
 
S u bjects will be f oll o we d f or 1 2 a d diti o nal wee ks or 8 4 da ys aft er last d ose if E T, after t h e 
d o u ble peri o d or t he O L E peri o d. 
 
S u bjects will re mai n at t he site f or at least 1 h o ur of o bser v ati o n f oll o wi n g t he e n d of t he 
S C i njecti o n.  
 
S u bjects will c o m plete a n u m ber of assess m e nts a n d q uesti o n naires, i ncl u di n g dail y e P R O, 
t hr o u g h o ut t he d urati o n of t h e st u d y. 
 
T otal st u d y d urati o n is a p pr o xi matel y 7 m o nt hs f or t he d o u ble- bli n d peri o d a n d 9 m o nt hs if 
t he s u bject c h o oses t o e nt er t h e O L E p eri o d. 
5. 2  
Sc he d ul e of E v e nts a n d St u d y Di a gr a m 
T he o verall sc he d ule of ass ess me nts a n d pr oce d ures is descri be d i n  Ta bl e 1. T he st u d y dia gra m 
is prese nte d i n Fi g ure 1. 






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A D A: 
A nti-lire nteli ma b a nti b o d y 
E O S: E n d of St u d y  
I R T: 
I nteracti ve Res p o nse Tec h n ol o g y 
 
  
F S H: F ollicle- Sti m ulati n g H or m o n e  
P K: 
P h ar mac o ki netics 
C B C: 
C o m plete Bl o o d C o u nt  
h C G: H u ma n C h ori o nic G o n a d otr o pi n  
 
  
  
I g E: I m m u n o gl o b uli n E 
  
E A SI: E cze m a Area a n d Se v erit y I n de x 
I P: 
I n v esti gati o n al Pr o d u ct  
vI G A: 
Vali date d I n v esti g at or’s Gl o bal Assess me nt 
E C G: 
Electr ocar di o gra m  
T a ble 1 N otes 
1) 
D ose 1 is t h e d a y of t h e first S C i njecti o n. D ose 1/ Da y 1 ca n o cc ur wit hi n a ± 3 d a y wi n d o w, i.e., t h e scree ni n g p eri o d ca n be a m a xi m u m of 1 7 d a ys a n d a mi ni m u m of 
1 1 da ys. D osi n g visits m ust be c o n d ucte d wit hi n t h e ± wi n d o ws sti p ulate d i n t h e pr ot oc ol.  
2) 
T he E O S visits s h o ul d b e c o n d u cte d 1 4, 5 6, a n d 8 4 ( ± 5) da ys after t h e last d ose of st u d y dr u g or pri or t o t his, if n ecessar y, t o e ns ure c o m plia n ce wit h t he visit. If t h e E O S visit 
o cc urs m ore t h a n 5 6 d a ys after t h e last d ose of st u d y dr u g, t he n p erf or m t he visit as s o o n as p ossi ble. T h e pr oce d ures liste d u n der t h e 1 4- d a y p ost-st u d y dr u g visit will b e 
c o n d ucte d u nless ot h er wise directe d b y t h e Me dical M o nit or. F or s u bjects p artici p ati n g i n t h e O L E peri o d, A E a n d c o n c o mita nt me dicati o ns s h o ul d be c ollecte d a n d rec or de d 
i n t he A K 0 0 2- 0 1 8 d o u ble bli n d treat me nt peri o d d ata base u p u ntil t h e start of t h e first o pe n-la bel S C i njecti o n after t h e Da y 9 9 visit. 
3) 
D oc u me ntati o n of A D dia g n osis a n d pre vi o us treat m e nts s h o ul d b e n ote d i n d etail. T his ca n b e s u bject re p orte d a n d/ or b ase d o n me dical rec or ds (see d etails i n Secti o n  1 2. 2. 6). 
4) 
At scree ni n g, hei g ht (i n c m) a n d wei g ht (i n k g) will b e rec or d e d. B o d y wei g ht will be meas ure d at e v er y visit. 
5) 
Vital si g ns will be m eas ure d at e v er y visit. O n all d osi n g d a ys: wit hi n 3 0 mi n utes pre d ose, 1 5 ( ± 5) mi n utes after a d mi nistrati o n of st u d y dr u g S C i njecti o n, a n d j ust pri or t o 
disc har g e. A d diti o nal vital si g n m eas ure me nts m a y b e c ollecte d at t h e I n v esti gat or’s discreti o n if a n i njecti o n-relate d reacti o n (I R R) o cc urs. 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 p erat ure, a n d res pirat or y rate will b e m eas ure d after t h e s u bject 
o btai ne d ( u nless c ollecte d f or a n I R R). 
6) 
A 1 0-lea d or 1 2-lea d E C G will be o btai n e d at scree ni n g b ef ore a n y bl o o d is dra w n a n d after t h e s u bject h as b ee n i n t he resti n g 
 
7) 
A c o m plete p h ysical e x a mi nati o n will b e perf or me d b y eit her t he I n vesti g at or or d esi g n ee a n d i ncl u d e t he f oll o wi n g b o d y s yste m or or g a n assess m e nts: s ki n; h ea d, e yes, ears, 
n ose, a n d t hr o at; 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 d es; a n d a brief ne ur ol o gical e xa mi n ati o n. A s y m pt o m- directe d p h ysical e x a m (i ncl u di n g 
assess me nt of p ossi ble i njecti o n site reacti o ns) will b e p erf or me d b y t h e I n v esti g at or or desi g n ee, as n ee d e d, if a n y s y m pt o ms are re p orte d. 
8) 
Acti vate P R O q u esti o n n aire a n d pr o vi d e s u bject wit h u ni q ue user na me a n d pass w or d. P R O q u esti o n n aire s h o ul d b e acti vate d f or all s u bjects o n scree ni n g Da y 1. 
9) 
D uri n g scree ni n g, vI G A, E A SI, 
 will b e d eter mi ne d, a n d a b aseli ne will b e esta blis he d. vI G A, E A SI, 
 m ust b e 
c o m plete d pre d ose o n d osi n g d a ys. T o e ns ure t h ere is s ufficie nt P R O d ata at b aseli n e, a s u bject s h o ul d c o m plete at least f o ur d ail y P R O q uesti o n n aires p er wee k f or a 
mi ni m u m peri o d of t he se ve n da ys pri or t o Da y 1. 
1 0) S u bjects will b e pr o m pte d t o a ns wer a d diti o n al q u esti o ns a b o ut s y m pt o ms relate d t o ast h ma, aller gic r hi nitis, a n d aller gic c o nj u ncti vitis ( At o pic C o n diti o ns Q u esti o n n aire). 
1 1) Bl o o d sa m ples f or t otal ser u m I g E will b e c ollecte d d uri n g scree ni n g, pre d ose o n Da ys 5 7 a n d 8 5, o n f oll o w- u p Da ys 9 9, 1 4 1, a n d 1 6 9, or 1 4, 5 6, a n d 8 4 ( ± 5) d a ys after t h e 
last d ose of st u d y dr u g if earl y ter mi nati o n ( E T). 


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T a ble 1 N otes c o nt.  
1 2) Bl o o d f or ser ol o g y testi n g will b e c ollecte d d uri n g scree ni n g a n d will i ncl u d e H Bs A g, h e p atitis C a nti b o d y, a nti- H Bc, a n d HI V. 
1 3) Fe male s u bjects of c hil d b eari n g p ote ntial are re q uire d t o ha ve h C G meas ure d. P ost m e n o pa usal w o me n are re q uire d t o h a v e F S H meas ure d. If 
n e g ati v e ser u m h C G will b e re q uire d d uri n g t h e scree ni n g p eri o d i n or d er f or s u bject t o pr ocee d t o ra n d o mizati o n. Bl o o d f or c h e mistr y will b e o btai n e d pre d ose o n d osi n g 
d a ys a n d f oll o w- u p da ys ( 1 4, 5 6, a n d 8 4 [ ± 5] d a ys after t he last d ose of st u d y dr u g if E T).  
1 4) Bl o o d f or C B C wit h differe ntial, i ncl u di n g a bs ol ute bl o o d e osi n o p hil c o u nt, will b e o btai ne d at scree ni n g, j ust pri or t o eac h S C i njecti o n, 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of 
eac h S C i njecti o n, a n d o n all f oll o w- u p d a ys ( 1 4, 5 6, a n d 8 4 [ ± 5] d a ys after last d ose if E T). All differe ntial bl o o d c o u nts fr o m Da y 1 ( p ost- d ose) t hr o u g h t he e n d of t h e 
s u bject’s partici pati o n i n t h e d o u ble- bli n d p eri o d will be bli n de d t o t he S p o ns or a n d t h e site. A n u nsc he d ule d C B C ma y be c ollecte d at t h e re q uest of t he Safet y M o nit or. 
1 5) Bl o o d f or P K will b e o btai n e d pre d ose o n all d osi n g d a ys as well as o n Da y 8 ( ± 3) a n d o n f oll o w- u p d a ys ( 1 4, 5 6 a n d 8 4 [ ± 5] d a ys after last d ose of st u d y dr u g if E T).
1 6) Bl o o d f or A D A will be c ollecte d pre d ose o n d osi n g Da ys 1, 4 3, a n d 8 5 ( ± 5), as well as o n Da y 8 ( ± 3), a n d o n f oll o w- u p Da ys 9 9 a n d 1 6 9 ( 1 4 a n d 8 4 [ ± 5] d a ys after last d ose 
of st u d y dr u g if E T). T h e A D A sa m ple will als o b e c ollecte d a n y ti m e a n i m m u n o ge nicit y-relate d A E occ urs. 
1 7) Uri ne will b e c ollecte d f or di pstic k pre g n a n c y test o n all d osi n g d a ys, Da y 8, a n d all f oll o w- u p d a ys ( 1 4, 5 6, a n d 8 4 d a ys after last d ose of st u d y dr u g if E T) f or all s u bjects of 
c hil d beari n g p ote ntial. Test kits will b e s u p plie d b y t h e ce ntral la b orat or y. T ests will b e c o m plete d o n site a n d e v al u ate d pri or t o eac h S C i njecti o n. 
1 8) Uri ne f or sta n dar d uri nal ysis will b e o btai n e d at scree ni n g a n d o n f oll o w- u p Da ys 9 9 a n d 1 6 9 ( 1 4 a n d 8 4 d a ys [ ± 5] if E T), a n d s y m pt o m- b ase d, as n ecessar y. 
1 9) Ra n d o mizati o n will be c o n d u cte d t hr o u g h t he I R T s yste m. S u bjects will b e ra n d o mize d 1: 1, lire nteli m a b S C 3 0 0 m g or place b o S C. T h e y will be stratifie d b ase d o n bi ol o gic 
stat us a n d I G A sc ore at b aseli ne. 
2 0) T h e ca pt ure of n o n-seri o us A E a n d a d v erse e ve nts of s pecial i nterest ( A E SI) will be gi n after t h e first d ose of st u d y dr u g h as o cc urre d. 
2 1) T h e re p orti n g of seri o us a d verse e v e nts ( S A E) o cc urri n g after si g ni n g t he I C F  a n d pri or t o t he first S C i njecti o n will be li mite d t o t h ose t h at relate t o scree ni n g pr oce d ures. T h e 
ca pt ure of all S A E a n d A E t h at are n ot relate d t o scree ni n g pr oce d ures will be gi n at t h e ti me of first S C i njecti o n of st u d y dr u g. F or s u bjects p artici p ati n g i n t h e O L E p eri o d, 
A E will b e assesse d a n d rec or d e d i n t h e C R F of t h e A K 0 0 2- 0 1 8 d o u ble- bli n d treat me nt p eri o d d ata b ase u p u ntil t h e start of t he first O L E S C i njecti o n, after t h e Da y 9 9 visit. 
T he A E will be rec or de d i n t he C R F of t h e A K 0 0 2- 0 1 8 O L E peri o d d ata b ase b e gi n ni n g wit h t h e start of t h e first o p e n-la bel S C i njecti o n after Da y 9 9. 
2 2) Lesi o n al a n d n o n-lesi o n al bi o psies will b e c ollecte d at selecte d U S sites a n d o nl y f or s u bjects w h o c o nse nt t o t his o pti o nal pr oce d ure. Bi o psies ma y be c ollecte d at baseli n e 
pre d ose o n Da y 1 a n d a gai n o n Da y 9 9/ Wee k 1 4. See Secti o n  1 2. 1. 1 0. 
2 3) O p e n-la b el e xte nsi o n d osi n g m a y start o n Da y 9 9 after all Da y 9 9 pr o ce d ures are c o n d u cte d or wit hi n 7 da ys after t h e Da y 9 9 visit. S u bjects w h o deci d e t o e nter t he O L E 
p eri o d a n d meet t he selecti o n criteria f or t h e O L E peri o d, will f oll o w t h e sc h e d ule of e v e nts i n  A p p e n di x 1 1 a n d d o n ot nee d t o re p eat Da y 9 9 pr o ce d ures if O L E Da y 1 visit is 
c o m plete d o n t he sa me d a y as Da y 9 9 visit. 


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Fi g ure 1
St u d y Di a gr a m
D B = D o u ble- Bli n d Peri o d; F U- F oll o w U p; S C =s u b c uta n e o us; O L E = O p e n L a bel E xte nsi o n; E O S = E n d of St u d y


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 4 7 of 1 3 5 
C o nfi d e nti al  
6.
Esti m a n d C o nsi der ati o ns 
T he esti m a n d f or t h e A K 0 0 2- 0 1 8 st u d y esti mates t he effect of tr eat m e nt, w hile c o nsi deri n g 
treat me nt a d here nce a n d res p o nse. T he esti ma n d will pr o vi de a n a ns wer t o t he q uesti o n t hat is 
cr ucial t o i n di vi d ual s u bjects: “If I ta ke t his st u d y me dicati o n as p art of m y treat m e nt re gi m e n, 
wit h o ut a d di n g a n y f urt h er dr u gs or e xit t h e st u d y pre mat urel y, w hat i m pr o v e me nt ca n I e x pect 
after 1 4 w ee ks?”
T ar get of Esti m ati o n 
C o nsiste nt wit h t he I C H E 9 A d de n d u m ( F D A, 2 0 2 1), defi niti o n of t he attri b utes of t h e esti m a n d 
(tar get of esti mati o n) is pr o vi de d i n t his secti o n. 
T he pri mar y esti m a n d of t he st u d y is a c o m p osite esti ma n d, w hic h esti mates t he effect of 
ra n d o mize d tr eat m e nt a n d acc o u nts f or n o n-res p o n ders b ase d u p o n i nterc urre nt e v e nts as 
defi ne d. 
P o p ul ati o n T ar gete d b y t he Scie ntific Q uesti o n 
T he p o p ulati o n tar gete d b y t he scie ntific q uesti o n is defi n e d via t he i n cl usi o n a n d e xcl usi o n 
criteria as part of t he st u d y pr ot oc ol. S u bjects ma y be male or fe male a n d m ust ha ve a cli nical 
dia g n osis of m o derate-t o-se vere A D i na d e q uat el y c o ntr olle d b y t o pical treat me nts as defi ne d b y 
t he st u d y i ncl usi o n crit eria. 
V ari a ble ( or E n d p oi nt) t o be O bt ai ne d f or E a c h S u bject t h at is Re q ui re d t o A d dress t he 
Scie ntific Q uesti o n
T he pri mar y e n d p oi nt t o be o btai n e d f or eac h s u bject i n t his st u d y t o a d dress t he scie ntific 
q uesti o n is t h e pr o p orti o n of s u bjects w h o ac hie v e E A SI- 7 5 at Wee k 1 4. F or partici pa nts w h o 
dr o p o ut or i nitiate resc u e or pr o hi bite d me dicati o n d uri n g t he st u d y, t he o utc o me will be defi ne d 
as “ n o n-res p o n der” aft er t he date of s uc h e ve nts. 
S pecific ati o n of H o w t o Acc o u nt f or I nterc ur re nt E ve nts t o Reflect t he Scie ntific Q uesti o n
of I nterest
T he f oll o wi n g i nterc urre nt e ve nts will be a ntici pate d a n d a d dresse d: 
Pre mat ure disc o nti n uati o n fr o m t he st u d y  
 
Use of pr o hi bite d me dicati o ns or resc ue t h era p y d uri n g t h e st u d y 
F or t he a nal ysis of t h e esti m a n d, s u bjects w h o pre mat urel y dis c o nti n ue t h e ra n d o mize d tr eat m e nt 
or i nitiate a n y resc ue or pr o hi bite d me dicati o n will be c o nsi dere d treat me nt n o n-res p o n ders at t h e 
desi g nate d ti me p oi nts after t he st art of s uc h treat m e nts .  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 4 8 of 1 3 5 
C o nfi d e nti al  
7.
Criteri a f or E v al u ati o n 
7. 1 
S afet y E n d p oi nts
T he safet y a n d t olera bilit y of lire nt eli m a b S C will be assesse d b y d eter mi ni n g t h e i n ci 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 E, wit h dra wals d ue t o A E, a n d c ha n g es i n vital 
si g ns, la b orat or y tests, c h a n g es i n c o nc o mita nt me dicati o n use d ue t o A E, i m m u n o ge nicit y, a n d 
ot her safet y p ara meters. T hese e n d p oi nts will b e base d o n t he f oll o wi n g:  
A d vers e e ve nts ( Secti o n 1 4. 1)  i ncl u di n g se verit y, wit h dra wals d ue t o A E, a n d ot her safet y 
para m eters. 
 
A d vers e e ve nts of s p ecial i nterest ( A E SI), i njecti o n-relate d reacti o ns (I R R), mali g na nc y, 
parasitic i nfecti o ns, a n d o p p ort u nistic i nfecti o ns ( Secti o n  1 4. 3) 
 
A nti- dr u g a nti b o dies ( Secti o n  1 2. 3. 6): 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.  
 
Bl o o d c he mistr y ( Secti o n  1 2. 3. 1) 
 
He mat ol o g y ( Secti o n  1 2. 3. 1) 
 
Uri nal ysis ( Secti o n  1 2. 3. 4) 
 
P h ysi cal e xa mi n ati o n ( Secti o n  1 2. 2. 2 a n d Secti o n  1 2. 2. 4) 
 
C ha n ges i n vital si g ns ( Secti o n  1 2. 2. 7) 
 
C ha n ges i n c o nc o mit a nt me dicati o n use d ue t o A E ( Secti o n  1 2. 2. 1)
7. 2  
P h ar m ac o ki netic E n d p oi nts  
Bl o o d (ser u m) will be c ollecte d f or assess me nt of lire nt eli m a b S C 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) m et h o d.  
T he P K bl o o d sa m ples will be o btai ne d pre d ose o n Da y 1 ( ± 3), D a y 8 ( ± 3), Da ys 1 5, 2 9, 4 3, 5 7, 
7 1, a n d 8 5 ( ± 5), a n d f oll o w- u p Da ys 9 9, 1 4 1, a n d 1 6 9 ( 1 4, 5 6, a n d 8 4 da ys [ ± 5] after t he last 
d ose if E T). A d diti o nal P K sa m ples will be c oll ect e d i n t he O L E peri o d of t h e st u d y pre d ose o n 
all d osi n g da ys.  
7. 2. 1  
Pri m ar y Effic ac y E n d p oi nts 
T he pri mar y efficac y e n d p oi nt i n t he st u d y will be pr o p orti o n of s u bjects w h o ac hie ve E A SI- 7 5 
at Wee k 1 4. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 4 9 of 1 3 5 
C o nfi d e nti al  
7. 2. 2 
S ec o n d ar y Effic ac y E n d p oi nts 
T he sec o n d ar y efficac y e n d p oi nts will be t h e f oll o wi n g: 
% C ha n ge i n E A SI fr o m baseli ne t o Wee k 1 4.
Pr o p orti o n of s u bjects wit h I G A of 0 or 1 a n d a 2- p oi nt i m pr o ve me nt at Wee k 1 4 c o m pare d
t o place b o.
7. 2. 3  
E x pl or at or y Effic ac y E n d p oi nts 
T he f oll o wi n g e x pl orat or y e n d p oi nts will be meas ure d: 
C ha n ge i n 
 at Wee k 1 4.
Ti me t o o nset of res p o ns e o n t he 
, w here
res p o nse is defi n e d as i m pr o ve me nt (at least a  
 re d ucti o n fr o m baseli n e) of wee kl y
a vera g e of d ail y  
 d uri n g t h e 1 4- wee k treat me nt peri o d. T he a n al ysis will be base d o n
s u bjects wit h a baseli ne  
.
C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
P D of lire nteli ma b S C i n s u bjects wit h A D as meas ure d b y c ha n g es fr o m b aseli ne i n
.
Ot her i n dices of effic ac y of lire nteli ma b S C i n s u bjects wit h A D. C h a n ges i n si g ns a n d
s y m pt o ms (c o m p are d t o baseli ne) bet w ee n lire nt eli ma b a n d place b o will b e meas ure d b y:
C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
C ha n ge i n  
 fr o m baseli ne t o Wee k 1 4
Pr o p orti o n of s u bjects w h o ac hie ve 
Pr o p orti o n of s u bjects w h o ac hie ve 
C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
C ha n ge fr o m baseli ne o v er ti me i n 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 0 of 1 3 5 
C o nfi d e nti al  
8.
S u bject Selecti o n
8. 1  
N u m ber of S u bjects 
A t otal of a p pr o xi m atel y 1 3 0 s u bjects wit h m o derate-t o-se v ere A D will be e nr olle d a n d 
ra n d o mize d i n a d o u ble- bli n d ma n ner, 1: 1, t o recei ve 1 of t he f oll o wi n g tr eat m e nts: 
 
Place b o S C a d mi nistere d e ver y 2 w ee ks  
 
Lire nteli ma b S C at 3 0 0 m g a d mi nistere d e ver y 2 wee ks  
E nr oll me nt will be m o nit ore d t o li mit t he i m pact of ra n d o mi zi n g a dis pr o p orti o natel y lar ge 
n u m ber of s u bjects wit h a n E A SI s c ore i n t he l o w er ra n g e, reflecti n g m ore m o derate disease o nl y 
(i.e., E A SI sc ore < 2 2). T his will als o pr o vi de a s u bject p o p ulati o n wit h a f ull ra n g e of E A SI 
sc ores c o nsiste nt wit h t he i nte nt t o st u d y lire nt eli m a b i n m o derate-t o-s e vere A D dis ease.
8. 2  
N u m ber of Sites 
U p t o 7 0 sites i n t he U nite d States a n d Ger ma n y will partici pate i n t his st u d y. 
Base d o n t he fee d bac k fr o m at o pic der matitis e x p erts a n d c o m plete d feasi bilit y assess me nts, it is 
e x pecte d t h at eac h site will be a ble t o scree n t hree s u bjects a n d e nr oll t w o of t he m i n t he d urati o n 
of t he e nr oll m e nt p eri o d. E nr oll me nt is c o nsi dere d t o be c o m petiti ve. T o e ns ure t he e nr oll me nt 
g oal is ac hi e ve d i n a ti mel y ma n ner, u p t o 7 0 sites (a p pr o xi matel y 5 5 i n t h e U S a n d 
a p pr o xi matel y 1 5 i n Ger ma n y) will be i niti ate d. If st u d y e nr oll m e nt rate ca n be ac hie v e d wit h 
fe wer sit es i n or der t o meet t he st u d y ti meli ne, t he n fe wer sites ma y be nee de d. 
8. 3  
St u d y P o p ul ati o n 
A p pr o xi matel y 1 3 0 male a n d fe male a d ult s u bjects wit h m o derate-t o-se v ere A D i na de q u atel y 
c o ntr olle d b y t o pical treat me nts will be e nr olle d i n t he st u d y. S u bjects will be eit her bi ol o gic-
naï ve or bi ol o gic-e x p os e d. Bi ol o gic-e x p ose d s u bjects i ncl u de t h ose w h o h a ve de m o nstrate d 
sec o n dar y l oss of res p o nse, i nt olera nce, or lac k of access t o bi ol o gics d ue t o ec o n o mic reas o ns. 
8. 4  
I ncl usi o n Criteri a 
S u bjects are eli gi ble f or t he st u d y if all of t he f oll o wi n g crit eria are met: 
1) 
S u bject is a ble t o u n dersta n d t he i nf or mati o n o n t h e st u d y, has t h e ca p acit y t o c o nse nt, a n d 
has pr o vi de d writt e n i nf or me d c o nse nt. 
2) 
 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 1 of 1 3 5 
C o nfi d e nti al  
3) 
C hr o nic A D (as d efi ne d b y t he A merica n A ca d e m y of D er mat ol o g y C o nse ns us Criteria) 
( Eic he nfiel d, 2 0 1 4); t h at has bee n prese nt f or at least 3 years bef ore s cree ni n g visit.  
4) 
D oc u m e nte d rece nt hist or y of i n a de q u ate res p o ns e t o treat m e nt wit h t o pical me dicati o ns 
s uc h as t o pical c ortic ost er oi ds, cal ci ne uri n i n hi bit ors, J A K i n hi bit ors, or P D E 4 i n hi bit ors 
(cris a b or ol e) f or at least 4 wee ks i n t he 6 m o nt hs pri or t o scree ni n g, or s u bjects f or w h o m 
t hese t o pical treat m e nts are ot her wis e m e dicall y i n a d vis a ble (e. g., b eca use of si de effects or 
safet y ris ks). 
5) 
S u bjects w h o are bi ol o gi c- naï ve or bi ol o gic-e x p os e d. Bi ol o gic-e x p ose d i ncl u des s u bjects 
w h o ha ve de m o nstr ate d s ec o n dar y l oss of res p o ns e, i nt olera n ce, or lac k of access t o 
bi ol o gics d ue t o ec o n o mic reas o ns. 
6) 
7) 
I n v ol ve m e nt of at least 1 0 % or m ore of B S A at scree ni n g a n d at baseli n e. 
8) 
A n I G A s c ore of 3 or a b o ve o n a scale fr o m 0 – 4 at scree ni n g a n d at baseli n e. 
9) 
T he s u bject s h o ul d ha ve a p plie d a st a ble d ose of n o n- me dicate d, n o n- pres cri pti o n, t o pical 
e m ollie nt at l east t wice d ail y f or 7 c o nsec uti ve da ys i m me diatel y bef ore t h e baseli ne visit.
1 0) 
Willi n g t o a p pl y a sta ble d ose of n o n- me dicate d, n o n- prescri pti o n, t o pical e m ollie nt, as
rec o m me n d e d b y t h e I n v esti g at or at least t wice d ail y f or t he d urati o n of t h e st u d y, if n ot 
alrea d y o n a n e m ollie nt at t he ti me of scree ni n g.  
1 1) 
C o m mit me nt t o re mai n o n t he s a me d ose(s) of A D me dicati o n(s), i n cl u di n g t o pical 
e m ollie nts, f or t h e e ntire d urati o n of st u d y partici p ati o n u nless d ose m o dificati o n is d ue t o 
u nf ores ee n me dical n ecessit y.
1 2) 
Willi n g a n d a ble t o c o m pl y wit h t he st u d y pr oce d ures a n d visit sc he d ule i n cl u di n g 
f oll o w- u p visits. 
1 3) Fe male s u bjects m ust be eit her p ost me n o pa usal ( d efi ne d as n o me ns es f or 1 2 m o nt hs 
wit h o ut a n alter nati v e m e dical ca use) wit h F S H le vel > 3 0 mI U/ m L at scree ni n g or 
s ur gicall y sterile (t u bal li g ati o n, h yst erect 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 nti al, ha ve a ne gati v e ser u m pre g n a nc y t est a n d a gree t o 
use a hi g hl y effecti ve met h o d of c o ntrace pti o n as defi ne d i n t his pr ot oc ol or a bstai n fr o m 
se x ual acti vit y, if c o m pli a nt wit h preferre d a n d us ual lifest yle of t h e s u bject, 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 o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 2 of 1 3 5 
C o nfi d e nti al  
t he s u bject will be re q uir e d t o ha ve a n e gati ve ser u m pre g na nc y test d uri n g t he scree ni n g 
peri o d a n d will als o be re q uire d t o ha ve a n e gati ve uri ne di pstic k pre g na n c y test pri or t o 
d osi n g a n d at eac h st u d y visit.
1 4) 
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 ntrace pti o n as defi ne d i n t his pr ot oc ol or a bstai n fr o m se x ual acti vit y 
fr o m scree ni n g u ntil t h e e n d of t he st u d y or f or 1 2 0 da ys f oll o wi n g t he last d ose of st u d y 
dr u g, w hic he v er is l o n ger. All fertil e me n wit h fe m ale part ners of c hil d beari n g p ote nti al 
s h o ul d be i nstr ucte d t o c o ntact t h e I n vesti g at or i m me diatel y if t he y s us pect t h eir part n er 
mi g ht be pre g na nt (e. g., misse d or late me nstr ual peri o d) at a n y ti me d uri n g st u d y 
partici pati o n. 
8. 5  
E xcl usi o n Criteri a 
S u bjects 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 crit eria: 
1) 
C urre nt use of bi ol o gics f or a n y i n dicati o n. 
2) 
De m o nstrate d lac k of pri m ar y res p o nse t o treat me nt wit h a bi ol o gic f or t h e treat m e nt of A D 
defi ne d as n o res p o nse t o treat me nt des pite c o m pl ete a d here n ce t o t he pres cri be d re gi me n 
f or at least 3 m o nt hs ( pri mar y n o n-res p o n d ers).  
3) 
Use of a n y of t he f oll o wi n g treat m e nts wit hi n 4 wee ks pri or t o t he bas eli n e visit or a n y 
c o n diti o n t h at i n t he o pi ni o n of t he I n vesti gat or is li kel y t o re q uire s uc h treat me nt(s) d uri n g 
t he first 4 wee ks of st u d y treat me nt: 
 P h ot ot hera p y f or A D 
 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 b ut n ot li mite d t o s yste mic 
calci ne uri n i n hi bit ors (e. g., c ycl os p ori n, tacr oli m us), m T O R i n hi bit ors (e. g., sir oli m us, 
e ver oli m us), a nti- meta b olites (e. g., azat hi o pri ne, m et h otre xate, 6- m erca pt o p uri ne, 
lefl u n o mi de, m yc o p he n olate m ofetil), al k ylati n g a ge nts (e. g., c ycl o p h os p ha mi d e), 
e osi n o p hil- de pleti n g dr u gs (e. g., pra mi pe x ole), a n d s yste mic c ortic oster oi ds 
 Oral J A K i n hi bit ors wit hi n 8 wee ks of t he b aseli n e visit (re q uires disc ussi o n wit h 
Alla k os Me dical M o nit or pri or t o s u bject e nr olli n g i n st u d y) 
4) 
Treat m e nt wit h bi ol o gics: 
 A n y cell- de pleti n g a ge nts i ncl u di n g b ut n ot li mite d t o rit u xi ma b; wit hi n 6 m o nt hs pri or 
t o t h e baseli ne visit, or u ntil l y m p h oc yte c o u nt ret ur ns t o n or mal, w hic he ver is l o n ger


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 3 of 1 3 5 
C o nfi d e nti al  
 T N F i n hi bit ors (e. g., i nfli xi ma b, a dali m u ma b) a n d ot her bi ol o gics (e. g., d u pil u ma b, 
o maliz u ma b, etc.) wit hi n 5 half-li ves if k n o w n or 8 wee ks pri or t o t he b aseli ne visit, 
w hic he ver is l o n ger 
5) 
A n y use of t o pical c ortic oster oi ds, t o pical calci ne uri n i n hi bit ors, t o pical J A K i n hi bit ors 
(e. g., r u x oliti ni b), or t o pical P D E 4 i n hi bit ors (cris a b or ole) f or t he treat m e nt of A D wit hi n 
1 wee k pri or t o t he b aseli n e visit.
6) 
Re g ular use ( m ore t ha n 2 visits per wee k) of a ta n ni n g b o ot h/ parl or wit hi n 4 wee ks of t he 
scree ni n g visit.
7)
Treat me nt wit h c h e m ot hera p y or ra di ot h era p y i n t he prec e di n g 6 m o nt hs.
8)
Prese nce of s ki n c o m or bi dities/c o nc o mita nt c o n diti o ns t hat ma y i nterfere wit h st u d y 
assess me nts or i nter pretati o n of st u d y res ults.
9)
Pl a n n e d or a ntici pate d us e of a n y pr o hi bite d me di cati o n.
1 0)
Hist or y of mali g na nc y e xce pt carci n o ma i n sit u i n t he cer vi x, earl y sta ge pr ostate ca ncer, or 
n o n- mela n o ma s ki n ca n cers.
1 1)
A n y disease, c o n diti o n ( me dical or s ur gic al), or car diac a b n or malit y t h at i n t he o pi ni o n of 
t he I n v esti gat or w o ul d pl ace t he s u bject at i ncreas e d ris k.
1 2)
A hel mi nt h parasitic i nfecti o n dia g n ose d wit hi n 6 m o nt hs pri or t o t he date i nf or me d c o ns e nt 
is o btai ne d t hat has n ot bee n treate d wit h or h as faile d t o res p o n d t o sta n dar d- of-care 
t hera p y.
1 3)
E vi de nce of acti v e he p atitis B or C at scree ni n g base d o n ser ol o g y.
1 4)
E vi de nce of acti v e HI V i nfecti o n at scree ni n g base d o n ser ol o g y.
1 5)
W o m e n w h o are pre g na nt, breastfee di n g, or pla n ni n g t o bec o me pre g n a nt w hil e 
partici pati n g i n t he st u d y.
1 6)
Prese nce of a n a b n or mal scree ni n g la b orat or y v al ue c o nsi dere d t o be cli nicall y si g nifica nt 
b y t he I n vesti gat or.
1 7)
K n o w n or s us pect e d hist or y of alc o h ol, dr u g, or ot her s u bsta nce a b use or d e pe n de nce t hat 
i n t h e o pi ni o n of t he I n v esti gat or ma y i nterfere wit h st u d y partici pati o n or assess me nts.
1 8)
Pri or e x p os ure t o lire nteli ma b or 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.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 4 of 1 3 5 
C o nfi d e nti al  
1 9)
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 h e last i nter ve nti o n occ urri n g wit hi n 
3 0 da ys pri or t o st u d y dr u g a d mi nistrati o n ( 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).
2 0)
S u bjects w h o wei g h < 4 0 k g at scree ni n g.
2 1) 
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 t he Me dical M o nit or ma kes t he 
s u bject u ns uita ble f or e nr oll m e nt.
2 2) 
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 m e nt i n 
t he st u d y, d uri n g t he treat me nt peri o d, or v acci n ati o n e x p ecte d wit hi n 5 half-li ves 
( 4 m o nt hs) of st u d y dr u g a d mi nistrati o n.  
N ote:  T his e xcl usi o n crit eri o n d oes n ot a p pl y t o all t y pes a n d f or m ulati o ns of vacci nes 
(i ncl u di n g li ve atte n uate d vacci n es) c urre ntl y a ut h orize d/a p pr o v e d b y F D A or ot her 
re g ulat or y a ut h orit y f or t he pre ve nti o n of C O VI D- 1 9, w hic h ma y be a d mi nist ere d 
bef ore, d uri n g, or after t h e st u d y.  
  
T he vacci ne s h o ul d n ot be a d mi nistere d wit hi n 3 d a ys bef ore a n d wit hi n 3 d a ys after 
t he a d mi nistrati o n of lire nteli ma b s o t hat a n y si d e effects ca us e d b y eit her of t he 
2 me dicati o ns ca n be m ore easil y det er mi ne d. 
2 3) 
E m pl o yees or rel ati v es of t he S p o ns or or t he I n v esti gat or, or ot her pers o ns d e pe n de nt o n t he 
S p o ns or or t he I n vesti gat or. 
2 4) 
C o m mit me nt t o a n i nstit uti o n b y or der iss ue d eit h er b y t he j u dicial or t h e a d mi nistrati v e 
a ut h orities. 
2 5) Prese nce of a S A R S- C o V- 2 i nfecti o n a n d/ or h a v e n ot c o m plete d a n a ut h orize d/a p pr o v e d 
C O VI D- 1 9 pri mar y i m m u nizati o n series as p er nati o nal rec o m me n d ati o ns at t h e ti me of 
scree ni n g. ( Ger m a n y o nl y) 
Acce pt a ble a n d re q uire d d oc u me ntati o n t o c o nfir m i ncl usi o n a n d e xcl usi o n crit eria is f urt h er 
e x plai n e d i n t he St u d y Refere nc e Ma n ual a n d list e d i n t he e C R F. 
8. 6  
S afet 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 E, 
i ncl u di n g a n y reacti o ns t o t he S C i njecti o n. All T E A E will be c oll ecte d fr o m t h e start of st u d y 
dr u g a d mi nistrati o n i n t h e d o u ble- bli n d peri o d of t he st u d y t hr o u g h t he st art of t he dr u g 
a d mi nistrati o n i n t he O L E peri o d, or t hr o u g h D a y 1 6 9 ( ± 5 da ys) or E T if s u bject is n ot e nr olli n g 
i n t h e O L E peri o d of t h e st u d y. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 5 of 1 3 5 
C o nfi d e nti al  
Se verit y will be assesse d usi n g t he N CI C T C A E, v ersi o n 5. 0, or m ost c urre nt versi o n. All A E 
will b e assi g ne d a s e verit y gra de a n d will be assesse d t o deter mi n e w h et her t he y are cli nicall y 
si g nifica nt a n d relat e d t o st u d y dr u g. 
A d diti o nal safet y e val u ati o ns i ncl u de cli nical la b orat or y tests c o m prisi n g A D A t o lire nteli ma b, 
c o m plete bl o o d c o u nts, c he mistries, a n d uri nal yses; p h ysical e xa ms; a n d vital si g n 
meas ure me nts. 
T he Me dical M o nit or will re vie w bli n de d safet y d ata t hr o u g h o ut t he st u d y. Certai n safet y d ata 
( p ost-treat m e nt cell differe nti als as well as tiss ue e osi n o p hil a n d mast cell c o u nts) will n ot be 
pr o vi de d t o st u d y sites or t o t he S p o ns or as it ma y ca use bias. T h e S afet y M o nit or will re vie w 
bli n de d safet y data as well as u n bli n de d cell c o u nts a n d will escalate t o t h e Me dical M o nit or as 
nee de d i n a m a n ner t h at d oes n ot ca us e bias.  
9.
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 b e d a n d o ver-t h e-c o u nter me dicati o ns 
ta ke n 3 0 da ys pri or t o t h e scree ni n g visit a n d will be rec or de d i n t he electr o nic Case Re p ort 
F or ms (e C R F). Pri or me dicati o ns a n d t h era pi es ta ke n f or t h e treat me nt of A D, e ve n if ta ke n
> 3 0 da ys bef ore t h e s cree ni n g visit, will be d oc u me nte d i n t he e C R F.  
F or s u bjects p arti ci pati n g i n t he O L E peri o d, c o n c o mita nt me dicati o ns s h o ul d be rec or de d i n t h e 
A K 0 0 2- 0 1 8 d o u ble- bli n d treat m e nt peri o d d ata bas e be gi n ni n g after t he first a d mi nistrati o n of 
st u d y dr u g i n t h e d o u ble- bli n d peri o d of t h e st u d y u p u ntil t h e first O L E d ose is a d mi nistere d 
after t he Da y 9 9 visit. 
A n y me dicati o ns t h at are e xcl usi o nar y s h o ul d be dis c o nti n ue d or ha n dle d as o utli ne d i n 
Secti o n  9. 1 of t he pr ot o c ol. 
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 ns, b ot h prescri be d a n d 
o ver-t h e-c o u nter, wit h o ut c o ns ulti n g t h e I n v esti gat or, u nless it is re q uire d f or e mer ge nc y use, or 
it is a C O VI D- 1 9 vacci n e. 
I m me diatel y pri or t o t he first S C i njecti o n, st u d y sit e pers o n nel s h o ul d e ns ure t h at t h e s u bject 
c o nti n ues t o meet all of t he i ncl usi o n criteria a n d n o ne of t he e x cl usi o n crit eria (i ncl u di n g use of 
pr o hi bite d me dicati o ns). 
All me dicati o ns ta ke n f or t he treat me nt of A D a n d a n y ot h er me dicati o ns ta ke n d uri n g t h e 
3 0 da ys pri or t o scree ni n g a n d d uri n g t h e st u d y m ust be d oc u m e nte d o n t he e C R F. All 
me dicati o ns use d t o treat I R R or A E d uri n g t h e st u d y m ust be d oc u me nte d.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 6 of 1 3 5 
C o nfi d e nti al  
All A E, w het her elicite d b y q uesti o ns fr o m st u d y staff, v ol u nteer e d, or n ot e d o n p h ysical 
e xa mi n ati 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 ass esse 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 t he first a d mi nistrati o n of st u d y dr u g i n t he d o u ble- bli n d 
peri o d of t he st u d y a n d e n di n g at t he ti me of st u d y c o m pleti o n or E T of t h e d o u ble- bli n d peri o d 
or t he O L E peri o d, w hic he ver is later. 
9. 1 
P r o hi bite d Me dic ati o ns 
T he i ntr o d ucti o n of m e di cati o ns or t hera pi es f or ot her m e dical c o n diti o ns k n o w n t o affect A D
(e. g., s yste mic c ortic oster oi ds, m y c o p he n olate- m ofetil, I F N- , J A K i n hi bit ors, t o pical 
c ortic oster oi ds [e xce pt w he n gi ve n f or resc u e t h era p y], t o pical calci ne uri n i n hi bit ors, 
c ycl os p ori ne, azat hi o pri n e, met h otre xate, p h ot ot hera p y, or p h ot oc he m ot hera p y) are n ot p er mitte d 
d uri n g t he st u d y a n d d uri n g t he i nter val pri or t o e ntr y i nt o t he st u d y as defi ne d i n t he e xcl usi o n 
criteria. 
Prescri pti o n e m ollie nts or e m ollie nts c o ntai ni n g a d diti ves s uc h as cera mi de, h yal ur o nic aci d, 
urea, or fila g gri n are n ot all o we d.  
I n a d diti o n, t h e use of ultra vi olet A or B ( U V A or U V B), ps orale n + U V A ( P U V A), ot her 
p h ot ot h era p y, or ta n ni n g be ds is n ot per mitte d d uri n g t he st u d y. 
T he use of 3 or m ore ble ac h bat hs per wee k is pr o hi bite d. 
Pla n ne d or a ntici pate d m aj or me dicati o n pr oce d ures or s ur geries s h o ul d be a v oi de d d uri n g t h e 
st u d y. 
S u bject will be re mi n de d t o n ot ta ke pr o hi bite d me dicati o ns a n d t o n otif y t he site i m me diatel y if 
a pr o hi bite d me dicati o n is prescri be d b y a n ot h er h ealt h care pr o vi d er. If a pr o hi bite d me dicati o n 
is starte d d uri n g t h e c o urse of t h e st u d y, t he s u bject ma y be wit h dra w n fr o m st u d y treat me nt a n d 
f oll o we d f or t he 1 2- wee k f oll o w- u p peri o d. 
9. 2  
All o we d Me dic ati o ns
Me dicati o ns ta ke n f or t he treat me nt of A D, s uc h as a nti hista mi nes, le u k otrie ne a nta g o nists, a n d 
s o di u m cr o m ol y n, are all o we d d uri n g t h e st u d y, u nless pr o hi bite d ( Secti o n  9. 1), a n d d oses are t o 
re mai n sta ble u nless c ha n ge is re q uire d f or a n u nf oresee n m e dical necessit y.
D uri n g t he 7 da ys pri or t o St u d y Da y 1, t he s u bject m ust ha ve use d, at least t wice dail y, n o n-
me dicate d t o pical t hera p y (i.e., e m ollie nt) wit h o ut ot h er acti ve i n gre die nts i n dicate d t o treat A D, 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 7 of 1 3 5 
C o nfi d e nti al  
or ot her a d diti v es w hic h c o ul d aff ect A D ( e. g., h y al ur o nic aci d, urea, cera mi d e or fila g gri n 
de gra dati o n pr o d u cts).
If t h e s u bject w as alrea d y usi n g a n o n- me dicate d t o pical t hera p y (i.e., e m ollie nt) at t h e ti me of 
scree ni n g, t he d os e, fre q ue nc y, a n d t y pe of m e dic ati o n s h o ul d be mai ntai ne d t hr o u g h o ut t he 
st u d y. If t h e s u bject is n ot usi n g t o pical e m olli e nts at t h e ti me of scree ni n g, t he I n v esti gat or will 
rec o m me n d a s uit a bl e n o n- me dicate d, n o n- pres cri pti o n t o pical e m olli e nt/ m oist urizer t h at s h o ul d 
be mai ntai n e d t hr o u g h o ut t he st u d y,
Me dicate d t o pical t hera p y is defi n e d as a t o pical pr o d uct t h at c o ntai ns a n acti ve p har mace uti cal 
i n gre die nt i n dicate d f or t h e treat m e nt of A D (re gar dless of w het her it is a n o ver-t he-c o u nter or 
prescri be d pr o d uct).  
All A D me dicati o ns use d d uri n g t he scree ni n g peri o d a n d t hr o u g h o ut t he st u d y will be 
d oc u me nte d i n t he C R F. A n y all o we d m e dic ati o ns t hat are ta k e n m ust re mai n sta ble t hr o u g h o ut 
t he st u d y. 
T he use of c o nc o mita nt me dicati o ns f or ot h er m e dical c o n diti o ns (e. g., h y perte nsi o n, dia betes, 
ac ute i nfecti o ns) is per mitte d d uri n g t his st u d y. Nasal ster oi ds a n d i n hale d c ortic oster oi ds t o 
c o ntr ol ast h ma are per mitte d. 
All t y pes a n d f or m ulati o ns of vacci n es (i ncl u di n g li ve atte n uate d v acci n es) c urre ntl y 
a ut h orize d/a p pr o ve d b y F D A or ot h er re g ulat or y a ut h orit y f or t he pre ve nti o n of C O VI D- 1 9 ma y 
be a d mi nistere d bef ore, d uri n g, or after t he st u d y.  
T he vacci n e s h o ul d n ot be a d mi nistere d wit hi n 3 d a ys bef ore a n d wit hi n 3 d a ys after t h e 
a d mi nistrati o n of lire nteli m a b s o t hat a n y si d e effects ca use d b y eit her of t h e 2 me dicati o ns ca n 
be m ore easil y deter mi ne d. 
9. 3  
Resc ue Me dic ati o ns 
T he use or i niti ati o n of a n y t o pical or s yste mic t hera p y f or t he p ur p os e of treati n g A D at a n y 
p oi nt i n t he st u d y will be c o nsi dere d resc u e t h era p y. Resc ue me dicati o ns are n ot all o we d d uri n g 
t he st u d y u nless me dicall y necessar y at t he discreti o n of t h e I n vesti gat or (i. e., t o treat flare- u ps of 
A D s y m pt o ms). Resc ue treat m e nt f or A D s y m pt o ms wit h ot her wise pr o hi bite d me dicati o ns ma y 
be pr o vi de d t o st u d y s u bjects at t he discreti o n of t he I n vesti gat or.
St u d y s u bjects re q uiri n g t o pical res c ue t hera p y wit hi n t h e first 4 wee ks of D ose 1 of t h e d o u ble-
bli n d peri o d will be dis c o nti n ue d fr o m t he st u d y b ut will be f oll o we d f or 1 2 wee ks. S u bjects 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 8 of 1 3 5 
C o nfi d e nti al  
re q uiri n g t o pical res c ue t hera p y after t he first 4 w ee ks f oll o wi n g D ose 1 will c o nti n ue wit h t he 
d ose re gi me n a n d b e f oll o we d t hr o u g h t he e n d of st u d y. 
St u d y s u bjects re q uiri n g s yste mic resc ue t h era p y d uri n g a n y p oi nt i n t he d o u ble- bli n d peri o d of 
t he st u d y will be dis c o nti n ue d fr o m t he st u d y b ut will be f oll o we d f or t he 1 2- wee k f oll o w- u p 
peri o d.  
1 0.
St u d y Tre at me nt
1 0. 1
F or m ul ati o n of Test P r o d u ct a n d Pl ace b o
Lire nteli m a b S C Dr u g Pr o d uct: T he lire nt eli ma b dr u g pr o d uct is i nte n de d f or s u bc uta n e o us 
i njecti o n. E ac h dr u g pr o d uct vial c o ntai ns a n o mi n al v ol u me of 1 m L. It is a steril e, preser vati ve-
free s ol uti o n t h at c o ntai ns
lire nteli ma b i n 
 
, p H 6. 0 i n 
Water f or I njecti o n ( W FI). T he s ol uti o n is vis uall y c haracteri ze d as clear t o sli g htl y o palesce nt, 
a p peari n g c ol orless t o sli g htl y yell o w.
Pl ace b o S C Pr o d u ct: T he place b o is i nte n de d f or s u bc uta ne o us i njecti o n. Eac h place b o vial 
c o ntai ns a n o mi nal v ol u me of 1 m L. It is a sterile, preser vati ve-free s ol uti o n t hat c o ntai ns 
 
 
, p H 6. 0 i n W FI. T h e s ol uti o n is vis uall y c haracterize d as clear t o sli g htl y 
o palesce nt, a p p eari n g c ol orless t o sli g htl y yell o w.
N ote : Lire nteli ma b S C a n d place b o S C will be referre d t o as “st u d y dr u g.”
Eac h d osi n g (lire nteli ma b S C or place b o S C) will c o m prise 1 S C i njecti o n of 2 m L of st u d y dr u g 
a d mi nistere d i n t he fr o nt of t h e t hi g h wit h a 2 7- ga u ge S C nee dle. M a xi m u m v ol u me 
a d mi nistere d per S C i njecti o n site will be 2 m L.
Lire nteli ma b S C or place b o S C ( base d o n ra n d o mi zati o n assi g n me nt) will be a d mi nistere d o n 
Da y 1 ( ± 3), D os e 1; Da y 1 5 ( ± 5), D ose 2; Da y 2 9 ( ± 5), D ose 3; Da y 4 3 ( ± 5), D ose 4; Da y 5 7 
( ± 5), D ose 5; Da y 7 1 ( ± 5), D ose 6; a n d D a y 8 5 ( ± 5), D ose 7.
S u bjects will ha ve t he o pti o n t o e nr oll i n a n O L E peri o d t o recei ve a n a d diti o nal 7 d oses of st u d y 
dr u g. S u bjects will be o bser ve d f or at least 1 h o ur after eac h i njecti o n.
D osi n g visits m ust be c o n d ucte d wit hi n t h e ± wi n d o ws sti p ulate d i n t he pr ot oc ol wit h t he 
f oll o wi n g re q uire me nts:


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 5 9 of 1 3 5 
C o nfi d e nti al  
 
T he i nter val bet w ee n d osi n g visits m ust be at least 7 da ys a n d n o m ore t h a n 2 1 da ys fr o m 
t he pre vi o us d osi n g visit u nless directe d ot her wise b y Alla k os. T he i nter val c o u nt starts t he 
da y after t h e visit a n d i ncl u des t he da y of t h e n e xt visit. 
 
T he i nter val bet w ee n t he fi nal d osi n g visit a n d t he efficac y visit ( Da y 9 9) m ust be at least 
1 1 da ys a n d n o m ore t ha n 1 7 da ys fr o m t he fi nal d osi n g visit u nless directe d ot her wis e b y 
Alla k os. T he i nter v al c o u nt starts t h e da y after t he visit a n d i n cl u des t he da y of t he ne xt 
visit. 
1 0. 2  
St u d y Dr u g P ac k a gi n g a n d L a beli n g
St u d y dr u g is s u p plie d i n 2 R T y pe I clear glass vials, sec urel y seale d wit h a fl u or o p ol y mer-
c oate d br o m o b ut yl st o p per a n d al u mi n u m fli p- off ca p. It is i nte n de d f or S C i njecti o n. T he vials 
are pac ke d i n cart o ns, a n d eac h cart o n c o nt ai ns 1 vial.
Eac h vial a n d eac h cart o n will be la bele d wit h all re q uire d d etails as per t h e a p plica ble l o cal 
re g ulati o ns. T he la bels will i n cl u de, a m o n g ot her details, a n i n vesti gati o nal use state me nt, l ot 
n u m ber, kit n u m ber, S p o ns or na me, a n d dir ecti o ns f or st ora ge. E ac h vial will als o c o ntai n a tear-
off la bel wit h kit n u m ber a n d s pace t o d o c u me nt Patie nt I D a n d dis pe nsi n g/ a d mi nistrati o n date. 
T his tear- off la bel s h o ul d be a p plie d t o t he I P I nje cti o n Dis p e nsi n g W or ks h eet a n d m ai ntai ne d 
wit h t h e s o urce d oc u m e nts.  
1 0. 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 sit es. T he i nitial st u d y dr u g 
s hi p me nt will be s hi p pe d aft er all re q uire d re g ulat or y d oc u me ntati o n a n d a p pr o vals ha ve b ee n 
recei v e d b y t he S p o ns or, t he c o ntract h as bee n e xec ute d, a n d t he first scree ne d s u bject is e ntere d 
i nt o t he I R T s yste m. S u bse q ue nt st u d y dr u g s hi p me nts will be tri g gere d a ut o mati call y base d o n 
pre deter mi n e d s u p pl y le vels a n d e nr oll me nt acti vit y at t he site.  
1 0. 4  
St u d y Dr u g D os e a n d D osi n g Re gi me n 
S u bjects will be ra n d o ml y assi g ne d t hr o u g h t he I R T s yste m t o a n acti ve d ose gr o u p of 7 d oses of 
lire nteli ma b S C or place b o S C ( Ta ble 2). T he d os e will be assi g ne d at t he ti me of ra n d o mizati o n.  
St u d y dr u g will c o m prise 1 S C i njecti o n of 2 m L a d mi nistere d i n t h e fr o nt of t he t hi g h wit h a 
2 7- ga u g e nee dle. Ma xi m u m v ol u me a d mi nistere d per S C i njecti o n will be 2 m L as i n dicate d i n 
t he st u d y P h ar mac y Ma n ual o n Da y 1 ( ± 3), D ose 1; Da y 1 5 ( ± 5), D ose 2; Da y 2 9 ( ± 5), D os e 3; 
Da y 4 3 ( ± 5), D os e 4; Da y 5 7 ( ± 5), D ose 5; Da y 7 1 ( ± 5), D ose 6; a n d D a y 8 5 ( ± 5), D ose 7. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 0 of 1 3 5 
C o nfi d e nti al  
S u bjects will ha ve t he o pti o n of g oi n g i nt o a n O L E peri o d t o recei ve a n a d diti o nal 7 d oses of 
acti v e st u d y dr u g. 
T a bl e 2 
St u d y Dr u g D os a ge
R o ute 
D ose 
( 7 D oses Bi wee kl y O v er 1 2 W ee ks) 
I njecti o n V ol u me/ D ose 
S u bc uta n e o us
3 0 0 m g Lire nteli ma b S C or Place b o S C
2 m L
1 0. 5
Pre p ar ati o n of St u d y Dr u g 
A st u d y p har macist or desi g nee will pre p are t he st u d y dr u g f or eac h S C i njecti o n base d o n t he 
assi g ne d d ose at ra n d o mizati o n. O n t he da y of d osi n g, t h e desi g nate d st u d y p har macist will 
pre pare lire nteli m a b or pl ace b o f or S C i njecti 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 dis pe nse d acc or di n g t o t he P har mac y Ma n ual f or A K 0 0 2- 0 1 8. Refer t o t h e 
P har mac y Ma n u al f or a d diti o nal details.  
Lire nteli ma b d oes n ot meet t h e defi niti o n of a “ hazar d o us dr u g ” a n d t h eref ore is n ot re q uire d t o 
be classifie d acc or di n g t o t h e U S P Hazar d o us Dr u g Gr o u pi n g. A dr u g is c o nsi d ere d t o be 
hazar d o us if it e x hi bits o ne or m ore of t h e f oll o wi n g c haracteristics i n h u m a ns or a ni mals: 
carci n o g e nicit y, terat o ge nicit y or de vel o p me ntal t o xicit y, re pr o d ucti ve t o xi cit y, or ga n t o xicit y at 
l o w d oses, ge n ot o xicit y, or str uct ure a n d t o xicit y pr ofiles of ne w dr u gs t hat mi mic e xisti n g 
hazar d o us dr u gs ( U S P, 2 0 1 9). Si n ce lire nteli ma b is n ot c o nsi d ere d t o be a h azar d o us dr u g, 
s pecial preca uti o ns d o n ot nee d t o be ta ke n w he n h a n dli n g or pre pari n g t he st u d y dr u g.  
1 0. 6  
St u d y Dr u g A d mi nistr ati o n 
S pecific i nstr ucti o ns o n a d mi nistrati o n a n d s u p plies re q uire d f or a d mi nistrati o n are detaile d i n 
t he P har mac y Ma n u al. I n ge neral, st u d y dr u g will c o m prise 1 S C i njecti o n a d mi nistere d i n t he 
fr o nt of t he t hi g h wit h a 2 7- ga u ge nee dle. S u bjects will be o bser ve d f or at least 1 h o ur aft er t h e 
S C i njecti o n a n d per t he I n v esti gat or’s discreti o n.  
1 0. 7  
St u d y Dr u g St or a ge 
St u d y dr u g will be st ore d b y t he st u d y sit es at 2° C t o 8º C u n der l oc k at t he d esi g nate d 
cli nic/ p har mac y l o cati o n. Access will be restricte d t o desi g nate d cli nic/ p har mac y staff. If t h e 
te m perat ure of st u d y dr u g st ora ge i n t he cli nic/ p h ar mac y e xcee ds or falls bel o w t his ra n ge, t he 
st u d y dr u g will b e q uara nti n e d a n d t he te m perat ure e xc ursi o n will be re p orte d t o t he S p o ns or or 
desi g nee. T he S p o ns or will n otif y t he site if t he st u d y dr u g ca n b e release d fr o m q uara nti ne. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 1 of 1 3 5 
C o nfi d e nti al  
1 0. 8
St u d y Dr u g Acc o u nt a bilit y
T he st u d y p har macist/ desi g nee is res p o nsi ble f or mai ntai ni n g acc urate a n d c urre nt rec or ds 
acc o u nti n g f or t h e recei pt, dis pe nsi n g, pre parati 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 n vesti gati o nal pr o d uct (I P). All d osa ge assi g n me nts a n d dis pe nsati o ns will be 
d oc u me nte d o n t he s o urce d oc u me nts. T he Mast er I P A cc o u nta bilit y L o g s h o ul d be use d t o 
ca pt ure recei pt, dis pe nsi n g, a n d ret ur n ( or destr u cti o n). Electr o nic I P acc o u nta bilit y s yste ms ma y 
be use d, d e pe n di n g o n site prefere n ce, as l o n g as t he sa me i nf or mati o n is ca pt ure d. T he st u d y 
m o nit or will verif y e ntries o n t hese d oc u me nts t hr o u g h o ut t h e c o urse of t he st u d y. St u d y dr u g 
will b e la bele d wit h kit n u m bers b ut will n ot re veal w het her t h e kit c o ntai ns acti ve dr u g or 
place b o. 
1 1.
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 1. 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 ne 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 nate 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 1 8. 
 
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 d esi g nate t he or der of c o ns e nt at t h e sit e (t he first s u bject w h o pr o vi d es 
c o nse nt is 0 0 1, t he sec o n d s u bject is 0 0 2, etc.). 
T he s u bject will mai ntai n t he s a me PI D t hr o u g h o ut t he st u d y. If a s u bject si g ns t h e I C F b ut d oes 
n ot meet t he i ncl usi o n/e xcl usi o n crit eria or q u alifies f or t h e st u d y b ut d oes n ot e nr oll, t he s u bject
ma y be assi g ne d a n e w PI D a n d rescree ne d o n ce. S u bjects rescree ne d wit hi n 3 0 da ys of si g ni n g 
t he i niti al c o nse nt will n ot nee d t o si g n a ne w I C F pr o vi di n g n o c ha n ges ha ve bee n ma de t o t h e 
I C F. 
1 1. 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 mi ze d i nt o t he st u d y, t he s u bject m ust ha ve c hr o ni c A D (acc or di n g t o t he A merica n 
Aca d e m y of Der mat ol o g y C o nse ns us Criteria,  A p pe n di x 1) t hat has bee n prese nt f or at least 
3 years bef ore t h e scree ni n g visit. T he s u bject m ust ha ve a n E A SI s c ore of 
1 6, t he s u bject’s A D 
m ust i n v ol ve at least 1 0 % or m ore of t h e B S A, al o n g wit h a n I G A sc ore of 3 or a b o ve o n a scale 
of 0 – 4. T he s u bject m ust als o meet all ot her a p plic a ble i ncl usi o n criteria a n d n o ne of t he 
e xcl usi o n crit eria. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 2 of 1 3 5 
C o nfi d e nti al  
If t h e 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 scree ni n g pr oce d ures, o n t h e da y 
of t he first S C i njecti o n ( D osi n g Da y 1), t he site will access t he I R T s yste m i n or der t o stratif y 
a n d ra n d o mize t h e s u bject i n t h e st u d y. T he I R T s yste m will t he n ra n d o ml y assi g n t he s u bject at 
a n all o cati o n rati o t o lire nteli m a b S C 3 0 0 m g, or place b o S C f or 7 d oses i n a d o u ble- bli n d 
ma n ner a n d will se n d a n e mail t o t he p har macist a n d/ or desi g nee det aili n g t h e kit n u m ber(s) t o 
use t o pre pare t he S C i njecti o n. 
T he s u bject will be stratifie d base d o n: 
1) 
Bi ol o gic- naï ve stat us vs. bi ol o gic-e x p ose d stat us 
2) 
I G A sc ore at bas eli ne: I G A sc ore of 3 vs I G A s c ore of 4
A p pr o xi matel y 1 3 0 s u bjects ( 6 5 per ar m) will be ra n d o mize d t o treat m e nt wit h lire nteli m a b S C 
or place b o S C. A s u bject is c o nsi d ere d e nr oll e d i n t he st u d y w he n t h e s u bje ct recei v es t h e first 
d ose of st u d y dr u g. F or s u bse q ue nt S C i njecti o ns t he c o or di nat or will access t he I R T s yste m o n 
t he da y of S C i njecti o n a n d e nter t h e PI D; t he s yst e m will assi g n t he s u bject t he d ose acc or di n g 
t o t h e s u bject’s ra n d o mizati o n n u m ber. T he p har macist a n d/ or desi g nee will t he n recei v e a n 
e mail detaili n g t he kit n u m ber(s) t o pre pare. 
Pri or t o eac h S C i njecti o n, t he I n v esti gat or or d esi g nee will c o nfir m t he PI D rec or de d o n t h e S C 
s yri n ge pr o vi de d b y t he p har macist matc hes t h e s u bject. T he patie nt i de ntifi cati 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 h e S C i njecti o n(s), 
w he ne ver p ossi ble. T here will n ot be a n y u n bli n di n g i nf or mati o n o n t he I R T n otificati o n t o t he 
p har macist or o n t h e vials pr o vi d e d t o t he site.  
T he assi g n me nt of treat me nt t o lire nteli ma b S C or place b o S C will be sec urel y retai ne d i n t h e 
I R T s yste m u ntil s uc h ti me as desi g nate d b y t he Statisti cal A nal ysis Pla n ( S A P).  
1 1. 3  
Bli n di n g 
T he i de ntit y of test a n d c o ntr ol treat m e 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 h e st u d y m o nit or. T he f oll o wi n g st u d y pr oce 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 m e nts: 
 
Access t o t he ra n d o mi zati o n c o des will b e strictl y c o ntr olle d b y t he I R T s yste m. 
 
T hr o u g h o ut t he d o u ble- bli n d st u d y, t he bli n d s h o ul d re mai n u n br o ke n e xce pt f or a n 
e mer ge n c y w he 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 na ge me nt or if re q uire d f or re g ulat 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 mer g e nc 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. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 3 of 1 3 5 
C o nfi d e nti al  
 
T he lire nteli ma b a n d place b o f or S C i njecti o n will be i de ntical i n a p peara nce. 
 
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 fi nal data b ase l oc k of t he d o u ble- bli n d st u d y.  
 
Res ults fr o m t he a nal ysis of bl o o d sa m ples f or hista mi ne/tr y ptase tests (c oll ecte d i n case of 
p ossi ble a na p h yla xis) will n ot be pr o vi de d t o t he I n vesti g at or a n d S p o ns or u ntil after fi nal 
data base l oc k of t h e d o u bl e- bli n d st u d y, u nless re q uire d f or i m me diate s afet y reas o ns.  
Res ults of t h e assess me nts n ote d bel o w will n ot be pr o vi d e d t o t he I n vesti gat or a n d S p o ns or 
u ntil after fi nal data b ase l oc k of t h e d o u ble- bli n d st u d y, s o as t o n ot i ntr o d uce bias. T he 
res ults will be re vie w e d o n a n o n g oi n g basis b y t he Safet y M o nit or a n d escalate d as 
a p pr o priate.  
 Differ e nti al cell c o u nts 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 ytes, a n d 
l y m p h oc ytes.  
Ot her t h a 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 veale 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 7. 4.
1 1. 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 st u d y o n a n e mer ge nc y basis b y t he site s h o ul d o nl y occ ur w he n 
k n o wle d ge of t he treat m e nt t o w hic h a s u bject w as all ocate d w o ul d ha ve i m plicati o ns f or t he 
e mer ge n c y me di cal ma na g e me nt of t he s u bject, if re q uire d f or re g ul at or y re p orti n g, or if t here is 
a pre g na n c y d uri n g t he pre g na nc y re p orti n g peri o d. 
If n ecess ar y, e mer g e nc y brea ki n g of t h e bli n d ca n be c o n d ucte d t hr o u g h t h e I R T b y t he 
I n v esti gat or or ot her re gistere d site users a n d/ or t h e Me dical M o nit or. W h e ne ver p ossi ble, t he 
I n v esti gat or s h o ul d c o ntact t he Me di cal M o nit or b ef ore a n e mer ge nc y brea ki n g of t h e 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, pers o n nel w h o k n o w t he u n bli n de d 
treat me nt, a n d dat e/ti m e of u n bli n di n g will be rec or de d. 
1 2.  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 assess me nts de pi cti n g t he re q uire d t esti n g pr oce d ures t o be 
perf or me d f or t h e d urati o n of t h e st u d y. W he n m ulti ple e val uati o ns are s c he d ule d at t he sa me 
ti m e p oi nt, t he pri orit y f or eac h will be as f oll o ws:  
 
At h o me: F or t he dail y q uesti o n naires t hat t he s u bject c o m pletes at h o me, t he s u bject 
s h o ul d c o m plete t he  
 e xce pt o n da ys of st u d y visits w he n t he  
 will be 
c o m plete d w hil e t h e s u bj ect is at t he st u d y sit e. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 4 of 1 3 5 
C o nfi d e nti al  
 
At t he cli nic:  
1)  
 I G A, E A SI, 
, a n d At o pic C o n diti o ns Q uesti o n naire. 
2) 
Vital si g ns will be o btai ne d after t he s u bject
 
3) P h ysical e xa mi nati o ns ca n be p erf or me d a n d uri ne sa m ples ca n be c ollecte d eit her 
bef ore or aft er ot her e val uati o ns, u nless ot her wise s pecifie d.  
1 2. 1
P h a r m ac o d y n a mic/ Effic ac y- R el ate d Pr oce d ures
T o e ns ure c o nsiste n c y i n gra di n g, t he s a me I n v esti gat or s h o ul d ma ke all ass ess m e nts f or a 
s u bject starti n g fr o m scree ni n g a n d c o nti n ui n g t hr o u g h o ut t he d o u ble- bli n d peri o d a n d O L E 
peri o d of t he st u d y w he n e ver p ossi ble. It will n ot be c o nsi dere d a pr ot oc ol de viati o n if a differe nt 
I n v esti gat or ma kes a n assess me nt f or a s u bject d uri n g t he st u d y, b ut t his s h o ul d be a v oi d e d as 
m uc h as p ossi ble. 
1 2. 1. 1  
V ali d ate d I n vesti g at or Gl o b al Ass ess me nt  
T he vali d ate d I n v esti gat or Gl o bal Assess me nt ( vI G A) is a 5- p oi nt scale t hat pr o vi des a gl o bal 
cli nical assess me nt of A D s e verit y ra n gi n g fr o m 0 t o 4 a n d assesses disease se verit y a n d cli nical 
res p o nse usi n g a 5- p oi nt scale: 0 = cl ear; 1 = al m ost clear; 2 = mil d; 3 = m o derate; a n d 
4 = se vere ( A p p e n di x 2) . T he sc ore is d eter mi n e d b y ra n ki n g t he e xte nt of er yt h e ma a n d 
pa p ulati o n/i nfiltrati o n. A decrease i n sc ore relates t o a n i m pr o ve me nt i n si g ns a n d s y m pt o ms. 
T he vI G A is a p h ysici a n-c o n d ucte d ass ess m e nt.  
T he vI G A will be d eter mi ne d d uri n g scree ni n g, a n d a baseli n e will be est a blis he d. A vI G A sc ore 
of 3 is re q uire d t o e nr oll i n t he st u d y. T he vI G A will be meas ure d b y I n v esti g at ors d uri n g 
scree ni n g, pre d ose o n all d osi n g da ys, a n d d uri n g eac h f oll o w- u p da y or E T.
1 2. 1. 2  
Ecze m a Are a a n d Se verit y I n de x
D uri n g scre e ni n g, t he E A SI will be deter mi ne d, a n d a baseli ne will be est a blis he d. T he E A SI 
sc ore is a t o ol use d t o meas ure t he e xte nt (area) a n d se verit y of at o pic ecze ma wit h res p ect t o 
er yt h e ma, e xc oriati o n, i nfiltrati o n, a n d lic he nificati o n at 4 a nat o mic sites of t he b o d y: l o wer a n d 
u p per e xtre miti es, tr u n k, a n d hea d ( A p pe n di x 3) . T he t otal E A SI s c ore will be i n a ra n g e fr o m 
0 t o 7 2 p oi nts (fr o m n o disease t o ma xi m u m disease se verit y) a n d is c o n d u cte d b y t he 
I n v esti gat or. A n E A SI s c ore of > 1 6 d uri n g scree ni n g is re q uire d t o e nr oll i n t h e st u d y. T he E A SI 
will b e deter mi ne d b y I n v esti gat ors d uri n g scree ni n g, pre d ose o n all d osi n g da ys, a n d d uri n g all
f oll o w- u p o n Da ys 9 9, 1 4 1, a n d 1 6 9 or E T.




Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 6 of 1 3 5 
C o nfi d e nti al  
o verall sc ori n g s yste m of  
; a hi g h sc ore is i n dicati v e of a 
is a 
self-a d mi nistere d q u esti o n naire. S u bjects will c o m plete t his d uri n g scree ni n g, pre d ose o n all 
d osi n g da ys, a n d d uri n g f oll o w- u p o n Da ys 9 9, 1 4 1, a n d 1 6 9 or E T. 
1 2. 1. 7
At o pic C o n diti o ns Q uesti o n n aire
O n Da y 1, Da y 9 9 a n d O L E Da y 9 9, s u bjects will be pr o m pte d t o a ns wer a d diti o nal q uesti o ns 
a b o ut se verit y of s y m pt o ms relate d t o ast h ma, aller gic r hi nitis a n d aller gic c o nj u ncti vitis 
( A p pe n di x 7).
1 2. 1. 8
P h ot o g r a p hs 
T he site staff ma y ta k e p h ot o gra p hs of s u bjects’ A D dis ease t o trac k st u d y dr u g res p o nse a n d 
disease pr o gressi o n. T his will de pe n d o n t he sites’ sta n dar d o perati n g pr oce d ures re g ar di n g 
p h ot o gra p h y. S u bjects will be c o nse nte d bef ore t h e S p o ns or will ha ve access t o a n y i ma ges. 
1 2. 1. 9  
C o m plete Bl o o d C o u nt wit h Differe nti al 
Bl o o d f or c o m plete bl o o d c o u nt ( C B C) wit h differe ntial, i ncl u di n g a bs ol ute bl o o d e osi n o p hil 
c o u nt, will be o btai ne d at scree ni n g, j ust pri or t o eac h S C i njecti o n, 1 h o ur ( ± 1 5 mi n utes) after 
t he e n d of eac h S C i njecti o n, a n d o n D a ys 9 9, 1 4 1, a n d 1 6 9 ( ± 5) or 1 4, 5 6, a n d 8 4 ( ± 5) d a ys after 
last d ose if E T. T he bl o o d sa m ple will be pr ocess e d a n d s hi p pe d i n acc or da nce wit h t h e 
La b orat or y M a n ual a n d l a b kit i nstr ucti o ns. A ce ntral la b orat or y will a n al yze t he bl o o d sa m ple 
a n d pr o vi de res ults f or C B C wit h differe ntial i ncl u di n g he m o gl o bi n, he mat ocrit, platelet c o u nt, 
re d bl o o d cell c o u nt, w hite bl o o d cell c o u nt, a n d a bs ol ute differe ntial c o u nt ( ne utr o p hils, 
l y m p h oc ytes, m o n oc ytes, e osi n o p hils, a n d bas o p hils).  
D uri n g t he d o u ble- bli n d peri o d, all differe nti al bl o o d c o u nts fr o m Da y 1 ( p ost- d ose) t hr o u g h t he 
e n d of t h e s u bject’s p arti ci pati o n will be bli n de d t o t he S p o ns or a n d t h e sit e. 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 Safet y M o nit or. T he bl o o d differe nti al test res ults 
( ne utr o p hils, e osi n o p hils, bas o p hils, m o n oc ytes, 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 t hr o u g h Da y 1 6 9 or E T a n d u ntil data base l o c k 
has occ urre d. If a s u bject c o nti n ues t o t he O L E p eri o d of t he st u d y, all differe ntial bl o o d c o u nts 
will b e bli n de d f or t he first ( O L E Da y 1) pre d ose assess me nts a n d will be u n bli n de d after t h e 
s u bject has recei ve d t h e first d ose of t h e st u d y dr u g. 
As descri b e d i n t he I n vesti gat or’s Br oc h ure, c ha n g es i n certai n la b res ults are a part of t he 
e x pecte d effects of lire nt eli m a b a n d c o ul d p ote ntiall y i ntr o d uce bias i n bli n de d me m bers of t he 
st u d y. T he Safet y M o nit or will ha ve real-ti m e access t o t hese la b orat or y res ults a n d will re vie w 
a n d escal ate a n y c o ncer ns/iss u es t o t he M e dical M o nit or a n d/ or t he site as a p pr o priate. A n 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 7 of 1 3 5 
C o nfi d e nti al  
u nsc he d ule d C B C wit h differe ntial ma y b e c olle cte d if re q u este d b y t he S afet y M o nit or. All 
pa nic alerts f or bli n de d v al ues will be se nt t o t he Safet y M o nit or a n d e v al uate d i n real ti me.
1 2. 1. 1 0
Fres h bi o psies
O pti o nal lesi o nal a n d n o n-lesi o nal bi o ps y sa m ples will be c ollecte d at sele cte d U S sites f or 
e x pl orat or y a n al ysis at baseli ne/ pre d ose o n Da y 1 a n d o n D a y 9 9/ W ee k 1 4 d uri n g t h e d o u ble-
bli n d peri o d. T hese fres h bi o psies will be s hi p pe d o ver ni g ht t o Alla k os f or a d diti o nal cell 
p he n ot y pi n g a n d ot her e x pl orat or y a nal ysis. O nce Alla k os recei v es t h e bi o psies, t he y will be 
diss ociate d i nt o si n gle cells a n d i m m u n o p he n ot y pe d f or i m m u ne cell p o p ulati o ns (l y m p h oc ytes, 
e osi n o p hils, b as o p hils, mast cells, ne utr o p hils, a n d macr o p ha g es) a n d ot her e x pl orat or y a nal ysis. 
Detaile d i nstr ucti o ns o n c oll ecti o n, pac ka gi n g a n d s hi p pi n g will be i n cl u de d i n t h e la b ma n ual. 
All materials re q uire d f or s hi p me nt of t he a d diti o nal sa m ples will be pr o vi de d t o t he site b y t he 
Ce ntral La b orat or y. S u bjects w h o c h o ose t o p artici pate will nee d t o si g n a s e parate I nf or mati o n 
a n d C o nse nt F or m. 
1 2. 2  
S afet y- R el ate d Pr o ce d u res 
1 2. 2. 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 are m a 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 di cati 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 bef ore scree ni n g a n d d uri n g t h e st u d y t hr o u g h Da y 1 6 9 ( 5 6 or 8 4 [ ± 5] da ys after last 
d ose of st u d y dr u g if E T) will be rec or d e d, or t hr o u g h t h e first d ose of st u d y dr u g if s u bject 
e nters t h e O L E p eri o d of t he st u d y.  
F or s u bjects p arti ci pati n g i n t he O L E peri o d, c o n c o mita nt me dicati o ns s h o ul d be rec or de d i n t he 
A K 0 0 2- 0 1 8 d o u ble- bli n d treat m e nt peri o d d ata bas e u p u ntil t he first O L E d ose is a d mi nistere d 
after t he Da y 9 9 visit. R esc ue m e dicati o ns a n d pr oce d ures m ust be d o c u me nte d as resc u e 
treat me nt i n t he s o urce d oc u me nts a n d o n t he Pri or a n d C o nc o mita nt Me dicati o ns e C R F.
A n y me dicati o ns ta ke n f or A D or A D-relate d s y m pt o ms at a n y ti me (e ve n if l o n ger t h a n 3 0 da ys 
bef ore s cre e ni n g) s h o ul d be liste d as c o nc o mita nt me dicati o ns, e ve n if t he me dicati o n was 
disc o nti n ue d pri or t o st u d y parti ci pati o n.
1 2. 2. 2
C o m pl ete 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 h er t h e I n vesti g at or or a q ualifie d desi g nee 
d uri n g t he scree 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 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 8 of 1 3 5 
C o nfi d e nti al  
or ga n assess me nts: s ki n; hea d, e y es, 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 n e ur ol o gical e x a mi n ati o n.  
1 2. 2. 3
B o d y Wei g ht a n d Hei 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 m eas ure d b y t he site a n d rec or de d. T h e 
site ca n n ot use val ues state d b y t he s u bject. B o d y wei g ht will als o be meas ure d o n all d osi n g a n d 
f oll o w- u p da ys or 1 4, 5 6, a n d 8 4 da ys aft er last d ose if E T.
1 2. 2. 4
S y m pt o m- Directe d P h ysi c al E x a mi n ati o n
A s y m pt o m- directe d p h ysical e xa m of re p orte d or o bser ve d s u bje ct s y m pt o ms warra nti n g 
e xa mi n ati o n i n t he o pi ni o n of t he I n vesti gat or, i n cl u di n g assess me nts of p ossi ble i njecti o n site 
reacti o ns a n d I R R, will b e perf or me d b y eit h er t h e I n v esti gat or or a q u alifie d desi g nee 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 peri o d. Ne w, a b n or mal p h ysical e xa 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 I n vesti gat or or S u bi n vesti g at or at t he 
ne xt sc he d ule d visit or s o o ner if cli nicall y i n dicate d or referre d t o a n o n-st u d y p h ysicia n.  
1 2. 2. 5  
Electr oc a r di o gr a m 
A n E C G will be o btai ne d d uri n g scree ni n g after t h e s u bject has bee n i n t he resti n g p ositi o n f or 
 mi n utes a n d bef ore a n y bl o o d dra w. T he I n v esti g at or or S u bi n vesti gat ors 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 nce. 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 diseases or c o n diti o ns t h at w o ul d p ut t h e s u bject 
at i ncreas e d ris k if partici pati n g i n a cli nical st u d y, s o t his s h o ul d be t a ke n i nt o c o nsi derati o n 
w he n e val u ati n g eli gi bilit y f or e ntr y i nt o t he st u d y. 
1 2. 2. 6
Pre vi o us A D Di a g n osis a n d Tre at me nts Re vie w
D uri n g t he scree ni n g visit t h e I n v esti gat or or desi g nee will c oll ect d oc u me ntati o n s u p p orti n g t h e 
c hr o nic A D di a g n osis a n d as k t he s u bject a b o ut t h e vari o us treat me nts or met h o ds of s y m pt o m 
c o ntr ol t hat t he y ha ve tri e d i n relati o n t o t h eir A D s y m pt o ms. T he treat me nts m a y i n cl u de 
me dicati o ns ( pres cri pti o n or o ver-t he-c o u nter), t h era pies (i.e., p h ot ot h era p y) or a da pti ve 
be ha vi ors, as w ell as alter nati ve me dici ne (i. e., ac u p u nct ure or h y p n otic t h era p y). A n y pre vi o us 
t hera pies a n d m e dicati o ns as relate d t o s u bjects’ A D disease will be rec or de d i n t h e st u d y C R F.
Re q uire d s pecifi c s o urce d oc u me ntati o n s u p p orti n g t he ass ess me nt of i ncl usi o n a n d e xcl usi o n 
criteria re gar di n g hist or y of A D dia g n osis a n d treat me nts will be t h e f oll o wi n g:
A c hr o nic A D dia g n osis f or at least 3 years (I ncl usi o n Criteria # 3) s h o ul d be c o nfir me d b y 
hist orical me dical rec or ds fr o m a der m at ol o gist, aller gist, or i m m u n ol o gist, or via c urre nt 
d oc u me ntati o n fr o m a st u d y der mat ol o gist, aller gist, or i m m u n ol o gist.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 6 9 of 1 3 5 
C o nfi d e nti al  
 
Me dical rec or ds d oc u m e nti n g t he t o pical A D treat m e nts a n d reas o n f or disc o nti n uati o n are 
re q uire d f or I ncl usi o n Criteria # 4. N otes fr o m p atie nt i nter vie w al o ne f or pre vi o us treat m e nt 
are n ot s ufficie nt. 
 
Der m at ol o gist or st u d y d oct or’s n otes re gar di n g A D treat me nt hist or y are n ee de d f or 
assessi n g I ncl usi o n criteria # 9 a n d E xcl usi o n Criteria # 2. 
M ore d etails are pr o vi de d i n t he i nstr ucti o n of t he Eli gi bilit y C R F pa ge. 
1 2. 2. 7  
Vit al Si g ns
Vital si g ns i n cl u di n g s yst olic a n d diast olic bl o o d press ure, p uls e, b o d y t e m perat ure, a n d 
res pirat or y rate will be ta ke n after t he s u bject
bl o o d dra w (e x ce pt f or p ost- S C i njecti o n w he n vital si g ns will be o btai ne d as descri be d b el o w).  
Vital si g ns will be meas ure d at scree ni n g, o n D a y 8 ( ± 3), o n all f oll o w- u p d a ys or 1 4, 5 6, a n d 8 4 
( ± 5) da ys after last d ose if E T, a n d o n all d osi n g d a ys wit hi n 3 0 mi n utes pre d ose, 
1 5 ( ± 5) mi n utes after c o m pleti o n of t he S C i njecti o n, a n d j ust pri or t o disc har g e. 
A d diti o nal vital si g ns meas ure me nts ma y be c ollecte d at t he I n v esti gat or’s discreti o n if a n I R R 
occ urs. Vital si g ns i ncl u di n g s yst oli c 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 m eas ure d after t h e s u bject 
bl o o d dra ws ha ve b ee n o btai n e d ( u nless c ollecte d f or a n I R R). 
Please refer t o t he sc he d ule of assess me nts i n  Ta bl e 1.  
1 2. 3
Cli nic al L a b or at or y Me as ure me nts  
Bl o o d a n d uri ne sa m ples f or cli nical safet y la b orat or y tests will be c ollecte d at t h e ti m e p oi nts 
descri b e d b el o w. I n vesti gat ors ma y ha ve a d diti o nal la b orat or y tests perf or me d f or t he p ur p os e of 
pla n ni n g treat me nt a d mi nistrati o n or f oll o wi n g A E or a b n or mal la b orat or y 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 yze bl o o d a n d uri n e sa m ples a n d pr o vi d e res ults f or t he 
cli nical safet y la b orat or y tests.  
Cli nical la b orat or y t esti n g ma y be perf or me d l ocall y, if necessar y, wit h pri or a p pr o val fr o m 
Alla k os. T he site will stri ve t o use t he ce ntral la b orat or y w he n e ver p ossi ble. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 0 of 1 3 5 
C o nfi d e nti al  
F or a n y l a b orat or y test v al ue o utsi d e t h e refere nce ra n ge, t h e I n vesti g at or will deter mi ne cli nical 
si g nifica n ce: N ot Cli nicall y Si g nifica nt ( N C S) or Cli nicall y Si g nifica nt ( C S). A n a b n or mal 
la b orat or y val u e s h o ul d be d ee me d C S if a n y of t h e f oll o wi n g c o n diti o ns are met: 
T he a b n or malit y s u g gests a disease a n d/ or or ga n t o xicit y t h at is ne w or has w ors e ne d fr o m 
baseli n e. 
 
T he a b n or malit y is of a d e gree t h at re q uires a d diti o nal acti ve ma na g e me nt, e. g., c ha n g e of 
st u d y dr u g d ose, disc o nti n uati o n of t he st u d y dr u g, cl ose o bser vati o n, m ore fre q ue nt 
f oll o w- u p assess me nts, or f urt her di a g n ostic i n vesti gati o n. 
T heref ore, a cli nicall y si g nifica nt la b orat or y v al u e is a la b test val ue t h at i n dicates a ne w disease 
pr ocess, a n e xacer b ati o n or w orse ni n g of a n e xisti n g c o n diti o n, or re q uires f urt her acti o n t o be 
ta ke n.  
F or a n y l a b orat or y test v al ue o utsi d e t h e refere nce ra n ge t h at t h e I n vesti g at or c o nsi d ers cli nicall y 
si g nifica nt, t he I n vesti gat or will:
 
Re peat t h e 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 h at: 
 T he I n vesti gat or c o nsi ders cli nicall y si g nifica nt. 
 Re q uires a s u bject t o be disc o nti n ue d fr o m t he st u d y. 
 Re q uires a s u bject t o recei ve treat m e nt.
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 2. 1. 9.
1 2. 3. 1
Bl o o d C he mistr y Pr ofile 
Bl o o d f or c he mistr y, i ncl u di n g h C G a n d F S H ( o nl y f or scree ni n g), will be c oll ecte d. O nl y 
s u bjects of c hil d beari n g p ote nti al a n d p ost me n o pa usal w o me n are re q uire d t o ha ve h C G or F S H 
testi n g (as descri be d i n S ecti o n 1 2. 3. 2). P ost me n o pa usal stat us m ust be c o nfir me d b y testi n g of 
F S H pri or t o t h e first d os e of st u d y dr u g re g ar dless of t he s u bject’s a g e. 
Bl o o d f or c he mistr y will be o btai ne d pre d os e o n all d osi n g da ys, as well as d uri n g scree ni n g, a n d 
o n Da ys 9 9, 1 4 1, a n d 1 6 9 or 1 4, 2 8, 5 6, a n d 8 4 ( ± 5) da ys after last d ose if 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 t he La b orat or y M a n u al 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 y ze t h e ser u m sa m ple a n d pr o vi de 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 1 of 1 3 5 
C o nfi d e nti al  
res ults f or c he mistr y tests i ncl u di n g s o di u m, p otassi u m, c hl ori de, bicar b o nate, gl uc ose, bl o o d 
urea nitr o g e n, creati ni ne, creati ne ki n ase, calci u m, p h os p h or us, ma g nesi u m, t otal a n d direct 
bilir u bi n, t otal pr otei n, al b u mi n, as partate a mi n otra nsferase ( A S T), ala ni ne a mi n otra nsferase 
( A L T), al k ali ne p h os p hat ase, ga m ma- gl uta m yl tra nsferas e ( G G T), a n d lact ate d e h y dr o g e nase.
1 2. 3. 2  
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 ( h C G le vel) will be c o m pl ete d f or all fe male s u bjects of c hil d beari n g 
p ote ntial at scree ni n g. W o me n w h o are s ur gicall y sterile (t u bal li g ati o n, partial or t otal 
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 m e n o pa us al 
f or at least 1 year wit h F S H le vel > 3 0 mI U/ m L are n ot c o nsi dere d t o b e of c hil d beari n g p ote ntial. 
At scree ni n g, F S H le vels will be teste d o n fe m ale s u bjects t o c o nfir m p ost m e n o pa usal stat us. 
B ot h F S H a n d h C G sa m ples will be pr ocesse d b y t he ce ntr al la b orat or y.
S u bject
mI U/ m L will be c o nsi dere d t o be of c hil d beari n g p ote ntial. Bl o o d 
will b e c ollecte d f or ser u m pre g na nc y test at scree ni n g. Uri ne will be c ollecte d f or di pstic k 
pre g n a nc y t est o n all d osi n g da ys, Da y 8, a n d all f oll o w- u p da ys ( 1 4, 5 6, a n d 8 4 da ys after last 
d ose of st u d y dr u g if E T) f or all s u bjects of c hil d b eari n g p ote ntial. Test kits will be s u p pli e d b y 
t he ce ntral la b orat or y. T ests will be c o m plete d o n site a n d e val uate d pri or t o eac h S C i njecti o n. If
a s u bject has a p ositi ve pre g na nc y t est, d osi n g will i m me diatel y be dis c o nti n ue d. 
T o e ns ure s u bject safet y, eac h pre g na n c y i n a s u bj ect t hat recei v e d st u d y dr u g m ust be re p orte d 
wit hi n 2 4 h o urs of lear ni n g of its occ urre nce. If t h e s u bject recei ve d lire nteli ma b S C, t h e 
pre g n a nc y s h o ul d b e f oll o we d t o deter mi ne o utc o me, i ncl u di n g s p o nta ne o us or v ol u ntar y 
ter mi nati o n, details of t he birt h, a n d t h e prese nce of a bse nc e of a n y birt h defects, c o n ge nit al 
a b n or malities, or mater nal a n d/ or ne w b or n c o m plicati o ns. If t h e s u bject recei ve d 
lire nteli ma b S C, a n y S A E e x p erie n ce d d uri n g pre g na nc y m ust be re p orte d o n t he S A E Re p ort 
F or m.  
1 2. 3. 3  
Effecti v e Met h o ds of C o ntr ace pti o n f or All a k os St u di es 
T his secti o n a p plies t o st u d y s u bjects w h o are w o me n of c hil d beari n g p ote nti al ( W O C B P) a n d 
male st u d y s u bjects w h ose se x ual part ners are W O C B P.
A p plic a ble f or St u d y Sites i n t he U nite d St ates: 
A bsti ne nce is t he o nl y birt h c o ntr ol met h o d t hat is 1 0 0 % effecti v e i n pre ve nti n g pre g n a nc y. F or 
s u bjects w h o d o n ot practice a bsti ne nce, Alla k os re q uires t h at st u d y s u bjects use hi g hl y effecti v e
met h o ds of c o ntrace pti o n, w hic h i ncl u de:
Per ma ne nt Sterilizati o n: T u bal li gati o n, vasect o m y – 9 9 % effecti ve 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 2 of 1 3 5 
C o nfi d e nti al  
 
L o n g- Acti n g Re versi ble C o ntrace pti v es ( L A R C):  
 I U D – 9 9 % effecti v e  
 I m pla nta ble r o d ( matc hstic k size d r o d t hat c o nt ai ns pr o g esti n h or m o ne i m pla nte d u n der 
t he s ki n of t he u p per ar m; pre ve nts o v ulati o n) – 9 9 % effecti ve 
 
C o ntrace pti ve I njecti o n: 
 I ntra m usc ular or s u bc uta ne o us i njecti o n of pr o gesti n h or m o ne e ver y 3 m o nt hs – 
9 6 % effecti v e  
 
S h ort- Acti n g H or m o nal Met h o ds:  
 Oral c o ntrace pti ves or patc h – 9 1 % effecti v e  
 Va gi nal c o ntrace pti v e ri n g (releases 2 h or m o nes, pr o gesti n a n d estr o ge n, t o pre ve nt 
o v ulati o n) – 9 1 % effecti ve  
N ote:  Effecti v e ness rates o btai ne d fr o m t he Birt h C o ntr ol G ui de o n t he F D A we b sit e 
( F D A, 2 0 2 1).  
Barrier a n d ot her m et h o ds n ot liste d a b o ve w he n us e d t o get her as d u al met h o ds s uc h as a 
c o n d o m + dia p hra g m or c o n d o m + s per mici d e are less effecti ve met h o ds, t heref ore t h ese d ual 
met h o ds are n ot rec o m me n de d as t h e y c o ul d i ncrease t he ris k of b ec o mi n g pre g na nt d uri n g t he 
st u d y or f oll o w- u p peri o d. W he n usi n g d ual met h o ds, at least 1 of t h e met h o ds s h o ul d be a 
hi g hl y effecti ve m et h o d of c o ntrace pti o n.  
A p plic a ble f or St u d y Sites i n Ger m a n y: 
Met h o ds t hat ca n ac hie ve a fail ure rate of less t ha n 1 % p er year w h e n use d c o nsiste ntl y a n d 
c orrectl y are c o nsi dere d as hi g hl y effecti ve birt h c o ntr ol met h o ds. Alla k os re q uires t h at st u d y 
s u bjects use hi g hl y effecti ve m et h o ds of c o ntrace pti o n, w hic h i n cl u de: 
 
C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o n1: Oral, i ntra va gi n al, or tra ns d er mal
 
Pr o gest o ge n- o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n 1: Oral, 
i njecta ble, or i m pla nta ble2  
 
I ntra uteri ne d e vice (I U D)2  
 
I ntra uteri ne h or m o ne-releasi n g s yste m (I U S)2  
 
Bil ateral t u bal occl usi o n 2


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 3 of 1 3 5 
C o nfi d e nti al  
 
Vasect o mis e d p art ner 2, 3
 
Se x ual a bsti ne nce 4
1) 
H or m o nal c o ntrace pti o n ma y be s usce pti ble t o i nteracti o n wit h t he st u d y dr u g, w hic h ma y 
re d u ce t h e efficac y of t h e c o ntrace pti o n met h o d. 
2) 
C o ntrace pti o n met h o ds t hat i n t he c o nte xt of t his g ui da nce are c o nsi d ere d t o ha ve l o w user 
de pe n de n c y.  
3) 
Vasect o mise d part ner is a hi g hl y effecti ve birt h c o ntr ol met h o d pr o vi de d t h at part ner is t he 
s ole se x ual part ner of t h e W O C B P trial parti ci pa nt a n d t hat t he vasect o mise d part ner h as 
recei v e d me dical assess me nt of t he s ur gical s ucc ess.  
4) 
I n t he c o nte xt of t his g ui da nce se x u al a bsti ne nce is c o nsi d ere d a hi g hl y effecti ve met h o d 
o nl y if defi n e d as refrai ni n g fr o m heter os e x ual i nterc o urs e d uri n g t he e ntir e peri o d of ris k 
ass ociate d wit h t he st u d y treat me nts. T he relia bilit y of se x ual a bsti ne nce nee ds t o be 
e val uate d i n relati o n t o t he d urati o n of t h e cli nical trial a n d t h e preferre d a n d us ual lifest yle 
of t he s u bject. 
N ote: 
Rec o m me n dati o ns relate d t o c o ntrace pti o n a n d pre g n a nc y testi n g i n cli nical trials 
( versi o n 1. 1) b y t h e Cli nical Trials Facilit ati o n a n d C o or di nati o n Gr o u p ( C T F G, 2 0 2 0).
1 2. 3. 4  
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 f oll o w- u p Da ys 9 9 a n d 1 6 9 ( 1 4 a n d 
8 4 [ ± 5] da ys f oll o wi n g last d ose if E T), a n d s y m pt o m- base d, as n ecess ar y. T he uri ne sa m ple will 
be pr ocess e d a n d s hi p pe d i n acc or da nce wit h t h e L a 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 y ze t h e uri ne sa m ple f or s p ecific gra vit y, p H, pr otei n, 
gl uc ose, ket o nes, bl o o d, a n d le u k oc yte esteras e.  
1 2. 3. 5  
Ser ol o g y 
Bl o o d will be o btai ne d at scree ni n g f or ser ol o g y tests i n cl u di n g he patitis B s urface a nti ge n 
( H Bs A G), he patitis C a nti b o d y, he patitis B c ore a nti b o d y (a nti- H B c), a n d h u ma n i m m u n o-
deficie nc y vir us ( HI V). T he bl o o d sa m ple will be pr ocess e 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 t he L a 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 or res ol ve d disease or e x p os ure) will e xcl u de t h e 
s u bject fr o m e nr oll me nt (A p pe n di x 1 0) .
1 2. 3. 6  
A nti- Lire nteli m a b A nti b o di es
Bl o o d f or deter mi n ati o n of A D A will be c ollecte d pre d ose o n d osi n g Da ys 1, 4 3, a n d 8 5 ( ± 5), o n 
Da y 8 ( ± 3), a n d o n f oll o w- u p Da ys 9 9 a n d 1 6 9 ( 1 4 a n d 8 4 [ ± 5] da ys after l ast d ose of st u d y dr u g 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 4 of 1 3 5 
C o nfi d e nti al  
if E T). T he A D A sa m ple will als o be c ollecte d a n y ti me a n i m m u n o ge nicit y-relate d A E occ urs.
A d diti o nal A D A sa m ples will be c oll ecte d at eac h d osi n g visit d uri n g t h e O L E peri o d. 
A n u nsc he d ule d bl o o d sa m ple 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 h e ser u m sa m ple will be c oll ecte d, pr ocesse d, a n d 
s hi p pe d i n acc or da nce wit h t he L a b orat or y M a n u al a n d l a b kit i nstr ucti o ns. A ce ntral la b orat or y 
will a nal yze t he sa m ple f or a nti-lire nteli ma b a nti b o dies usi n g a vali date d assa y m et h o d.
A d diti o nall y, t he ser u m sa m ples c ollecte d f or A D A will be retai n e d f or f ut ure testi n g i n t h e e ve nt 
t hat a n y ne w p ote nti al safet y or i m m u n o ge nicit y iss ues are i de ntifie d. 
1 2. 3. 7  
Bl o o d f or P h a r m ac o ki neti cs  
Bl o o d sa m ples f or ser u m P K ass ess me nts will be c ollecte d pre d ose o n d osi n g Da ys 1, 1 5, 2 9, 4 3, 
5 7, 7 1, a n d 8 5 ( ± 5) as w ell as o n Da y 8 ( ± 3) a n d d uri n g f oll o w- u p o n Da ys 9 9, 1 4 1, a n d 1 6 9 ( ± 5) 
or 1 4, 5 6, a n d 8 4 ( ± 5) d a ys after last d ose of st u d y dr u g if E T. T he ser u m sa m ples will be 
c ollecte d pre d ose a n d pr ocess e d a n d s hi p p e d fr oze n i n acc or da nce wit h t he La b orat or y M a n ual 
a n d la b kit i nstr ucti o ns. 
Lire nteli ma b 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 met h o d.  S pecific i nf or m ati o n o n P K sa m ple c oll ecti 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 la b orat or y ma n u al.  
1 2. 3. 8  
Bl o o d f or I g E 
Bl o o d will be c ollecte d f or deter mi nati o n of ser u m I g E le v els a n d se nt t o t h e ce ntr al la b orat or y 
f or pr ocessi n g. Bl o o d will be c ollecte d d uri n g s cree ni n g, pre d ose o n D a y 5 7 a n d Da y 8 5, a n d o n 
f oll o w- u p Da ys 9 9, 1 4 1, a n d 1 6 9 or 1 4, 5 6, a n d 8 5 ( ± 5) da ys after last d ose of st u d y dr u g if E T.  
1 2. 3. 9  
C O VI D- 1 9 Testi n g 
Testi n g f or C O VI D- 1 9 is n ot re q uire d f or t his st u d y b ut ma y be i m ple me nt e d b y t h e st u d y site at 
a n y ti me d uri n g t he st u d y d ue t o safet y re g ulati o ns or pr oce d ures. Testi n g f or C O VI D- 1 9 ma y b e 
i n di vi d uall y ma n date d b y facilities or b y state or c o u ntr y (e. g., Ger ma n y) re g ulati o n, a n d if 
re q uire d, t his will be c o nse nte d t hr o u g h t he site a n d n ot liste d i n t he A K 0 0 2- 0 1 8 I C F. Testi n g f or 
C O VI D- 1 9 ma y b e perf or me d acc or di n g t o t he tri al site st a n dar d pr oce d ures a n d safet y 
re g ulati o ns.  
T he ris k assess me nt relat e d t o o n g oi n g C o vi d- 1 9 pa n de mic will be re vi e w e d o n a c o nti n u o us 
basis, a n d meas ures re q uire d f or re d uci n g t h e ris k of i nfecti o n wit h t he n o v el c or o na vir us will be 
ta ke n, as a p pr o priate. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 5 of 1 3 5 
C o nfi d e nti al  
1 3.
E v al u ati o ns a n d P r oce d ures b y Visit
E val uati o ns a n d pr oce d ures b y visit are s h o w n i n Ta ble 1.  
Ge neral I nf or m ati o n: 
 
All rec or d e d cl oc k ti m es s h o ul d utilize a 2 4- h o ur cl o c k. 
 
Pr oce d ures f or scree ni n g ma y be perf or me d o ver t h e c o urse of m ulti ple visits pri or t o t h e 
first S C i njecti o n. 
 
D ose 1 is t he da y of t he first S C i njecti o n. D ose 1/ Da y 1 ca n o cc ur wit hi n a ± 3 da y wi n d o w, 
i.e., t he scre e ni n g peri o d ca n be a ma xi m u m of 1 7 da ys a n d a mi ni m u m of 1 1 da ys. D osi n g 
visits m ust be c o n d ucte d wit hi n t h e ± wi n d o ws sti p ulate d i n t he pr ot oc ol wit h t he f oll o wi n g 
re q uire me nts: 
 T he i nter val bet w ee n d osi n g visits m ust be at least 7 da ys a n d n o m ore t h a n 2 1 da ys 
fr o m t he pre vi o us d osi n g visit u nless directe d ot her wise b y Alla k os. T he i nt er val c o u nt 
starts t he da y aft er t he visit a n d i ncl u des t he da y of t he n e xt visit. 
 T he i nter val bet w ee n t he fi nal d osi n g visit a n d t he efficac y visit ( Da y 9 9) m ust be at 
least 1 1 da ys a n d n o m ore t h a n 1 7 da ys fr o m t he fi nal d osi n g visit u nless directe d 
ot her wise b y Alla k os. T h e i nter val c o u nt starts t he da y after t he visit a n d i n cl u des t he 
da y of t h e ne xt visit. 
 
F or D a y 8, t he visit ca n o cc ur wit hi n a ± 3 da y wi n d o w. 
1 3. 1  
Scree ni n g D a y ( ~ D a y - 1 4)/ Scree ni n g Peri o d 
1) 
O btai n writt e n i nf or me d c o nse nt. 
2) 
Assi g n t he partici pa nt a PI D. 
3) 
C oll ect d e m o gra p hics. 
4) 
O btai n me dical hist or y. 
5) 
Gat her a n d re vie w A D di a g n osis a n d detaile d pre vi o us treat me nt hist or y a n d c o nc o mita nts 
me dicati o ns ( Secti o n  1 2. 2. 6). 
6) 
C oll ect b o d y wei g ht (i n k g) a n d hei g ht (i n c m) al o n g wit h vital si g ns. 
7) 
Perf or m E C G. 
8) 
C o n d uct c o m plete p h ysical e xa mi nati o n. 
9) 
C oll ect vI G A, E A SI, 
.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 6 of 1 3 5 
C o nfi d e nti al  
1 0)
Acti vate dail y P R O a n d h a ve s u bject c o m plet e first P R O ( p p N R S) i n t he cli nic. T o e ns ure 
t here is s ufficie nt P R O d ata at baseli ne, a s u bject s h o ul d c o m plete at least f o ur dail y P R O 
q uesti o n naires per wee k f or a mi ni m u m peri o d of t he se ve n da ys pri or t o D a y 1.
1 1)
Ha ve s u bject c o m plete t h e  
q u esti o n naire a n d a ns wer 2  
 q u esti o ns.
1 2) 
C ollect bl o o d f or ser ol o g y, ser u m I g E, c he mistr y (i ncl u di n g h C G a n d F S H, if a p pli ca ble),
a n d C B C. Fe male s u bjects of c hil d beari n g p ote ntial are re q uire d t o ha ve h C G meas ure d. 
P ost me n o pa usal w o me n are re q uire d t o ha ve F S H meas ure d. If t he p ost me n o pa usal F S H 
. 
1 3) 
C ollect uri ne f or uri nal ysis. 
1 4) 
C o n d uct eli gi bilit y assess m e nt a n d c o nfir m s u bject is eli gi ble t o m o ve f or war d wit h 
scree ni n g. 
1 3. 2  
D a y 1 – R a n d o mi z ati o n/ D ose 1/ B aseli ne 
Pri or t o St u d y Dr u g A d mi nistrati o n: 
1) 
Assess t he s u bject f or S A E relate d t o scree ni n g pr o ce d ures. 
2) 
C o nfir m c o nti n ui n g eli gi bilit y a n d a vaila bilit y of all re q uire d me dical rec or ds a n d s o urce 
d oc u me nts. 
3) 
D oc u m e nt a n y c h a n ges t o healt h stat us. 
4) 
D oc u m e nt a n y c h a n ges t o me dical hist or y a n d c o nc o mita nt me dicati o ns. 
5) 
Assess  
 c o m plia nce. S u bject s h o ul d c o m plete at least f o ur d ail y P R O q uesti o n naires 
d uri n g t he se ve n da ys pri or t o Da y 1. 
6) 
Perf or m uri ne di pstic k pre g n a nc y test if s u bject is of c hil d beari n g p ote ntial. 
7) 
C oll ect b o d y wei g ht (i n k g). 
8) 
Perf or m s y m pt o m- direct e d p h ysical e xa m, if n ee d e d. 
9) 
C o m plete vI G A, E A SI, 
 
1 0) 
Ha ve s u bject c o m plete t h e  
 q u esti o n naire,  
 ( u nless alrea d y c o m plete d), a n d 
At o pic C o n diti o ns Q uesti o n naire. 
1 1) If c o nse nt is o btai ne d, c ollect bi o ps y (a p plica ble f or select e d U S sites o nl y).
1 2) 
Ra n d o mizati o n: 
a) 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 I n v esti gat or will d eter mi ne 
s u bject’s I G A s c ore a n d bi ol o gic- naï ve vs bi ol o gic-e x p ose d stat us i n or d er t o stratif y 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 7 of 1 3 5 
C o nfi d e nti al  
s u bject a n d si g n s o urce Eli gi bilit y F or m. T he st u d y c o or di nat or or d esi g nee will e nter 
I G A sc ore a n d bi ol o gic stat us i nt o t h e I R T o n St u d y Da y 1 t o stratif y t he s u bject.  
b)
T he I R T s yste m will t he n ra n d o ml y assi g n t he s u bject t o lire nteli m a b S C 3 0 0 m g or 
place b o S C i n a d o u ble- bli n d ma n ner a n d will se n d a n e mail t o t h e p har macist a n d/ or 
desi g nee detaili n g t h e kit n u m ber(s) t o use t o pre p are t he i njecti o n. See t h e P h ar m ac y 
Ma n ual f or detaile d S C i njecti o n pre parati o ns.
1 3) 
C ollect vit al si g ns wit hi n 3 0 mi n utes of t h e start of t he S C i njecti o n.
1 4) 
C ollect bl o o d f or C B C, c he mistr y, P K, a n d A D A j ust pri or t o S C i njecti o n. 
1 5) S C I njecti o n of St u d y Dr u g: 
a) S u bc uta ne o us d osi n g (lire nteli ma b S C or place b o S C) c o m prises 1 S C i njecti o n 
a d mi nistere d i n t he fr o nt of t h e t hi g h wit h a 2 7- ga u ge nee dle. M a xi m u m v ol u me 
a d mi nistere d per S C i njecti o n will be 2 m L. See t h e P h ar mac y M a n ual f or S C i njecti o n 
i nstr ucti o ns. 
b) C ollect vit al si g ns 1 5 ( ± 5) mi n utes after st u d y dr u g a d mi nistrati o n. 
1 6) P ost- S C I njecti o n:
a)
C ollect bl o o d f or C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after S C i njecti o n.
b) 
O bser ve t he s u bj ect f or at least 1 h o ur after st u d y dr u g a d mi nistrati o n. 
c) 
C ollect vit al si g ns j ust pri or t o disc har ge. 
If a n a p hyl axis is s us pecte d, a s a m ple of bl o o d s h o ul d be o bt ai ne d f or pl as m a hist a mi ne level a n d 
try pt ase wit hi n 1 – 2 h o urs of t h e o nset of sy m pt o ms. Als o, a n u nsc he d ule d A D A bl o o d s a m ple 
m ay b e o bt ai ne d if a n i m m u n o ge nicity-rel ate d A E is s us pecte d. 
1 3. 3
D a y 8 ( ± 3)  
1) 
Assess t he s u bject f or A E a n d S A E. 
2) 
D oc u m e nt a n y c h a n ges t o c o nc o mita nt me dicati o ns. 
3) 
Assess  
 c o m plia nce. 
4) 
C oll ect vital si g ns a n d b o d y wei g ht (i n k g).
5) 
C oll ect bl o o d f or P K a n d A D A
6) 
Perf or m uri ne di pstic k pre g n a nc y test if s u bject is of c hil d beari n g p ote ntial.
7) 
Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 8 of 1 3 5 
C o nfi d e nti al  
1 3. 4
D a y 1 5 ( ± 5) – D ose 2
1) 
Pri or t o S C I njecti o n:
a)
Assess t he s u bject f or A E a n d S A E. 
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)
Assess 
 c o m plia nce.
d)
C o m plete I G A, E A SI, 
 assess me nts.
e)
Ha ve s u bject c o m plete  
 a n d  
a n d 2 q u esti o ns o n t he  
 
q uesti o n naire.
f) 
C ollect b o d y wei g ht (i n k g). 
g) 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. 
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d. 
2) 
S C I njecti o n of St u d y Dr u g: 
a) E nter t h e visit i n t h e I R T a n d pre pare st u d y dr u g usi n g kit n u m ber(s) pr o vi de d b y t he 
I R T. See t h e P h ar mac y Ma n ual f or det aile d S C i njecti o n pre parati o ns. 
b) C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t h e start of t he S C i njecti o n. 
c) 
C ollect bl o o d f or C B C, c he mistr y, a n d P K j ust pri or t o t he S C i njecti o n. 
d) 
A d mi nister S C i njecti o n i n t h e fr o nt of t he t hi g h. 
e) 
C ollect vit al si g ns 1 5 ( ± 5) mi n utes after st u d y dr u g a d mi nistrati o n. 
3) 
P ost- S C I njecti o n: 
a) 
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e S C i njecti o n. 
b) 
O bser ve t he s u bj ect f or at least 1 h o ur after st u d y dr u g a d mi nistrati o n.  
c) 
C ollect vit al si g ns j ust pri or t o disc har ge. 
If a n a p hyl axis is s us pecte d, a s a m ple of bl o o d s h o ul d be o bt ai ne d f or pl as m a hist a mi ne level a n d 
try pt ase wit hi n 1 – 2 h o urs of t h e o nset of sy m pt o ms. Als o, a n u nsc he d ule d A D A bl o o d s a m ple 
m ay b e o bt ai ne d if a n i m m u n o ge nicity-rel ate d A E is s us pecte d. 
1 3. 5  
D a y 2 9 ( ± 5) – D ose 3 
1) 
Pri or t o S C I njecti o n: 
a) 
Assess t he s u bject f or A E a n d S A E. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 7 9 of 1 3 5 
C o nfi d e nti al  
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) 
Assess  
 c o m plia nce.
d)
Perf or m I G A, E A SI, 
assess me nts.
e)
Ha ve s u bject c o m plete  
 a n d  
a n d 2 q u esti o ns o n t he  
 
q uesti o n naire. 
f)
C ollect b o d y wei g ht (i n k g).
g) 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. 
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d. 
2) 
S C I njecti o n of St u d y Dr u g: 
a) E nter t h e visit i n t h e I R T a n d pre pare st u d y dr u g usi n g kit n u m ber(s) pr o vi de d b y t he 
I R T. See t h e P h ar mac y Ma n ual f or det aile d S C i njecti o n pre parati o ns. 
b) C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t h e start of t he S C i njecti o n. 
c) 
C ollect bl o o d f or C B C, c he mistr y, a n d P K j ust pri or t o t he S C i njecti o n. 
d) 
A d mi nister S C i njecti o n i n t h e fr o nt of t he t hi g h. 
e) 
C ollect vit al si g ns 1 5 ( ± 5) mi n utes after t h e st u d y dr u g a d mi nistrati o n. 
3) 
P ost- S C I njecti o n:
a)
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e S C i njecti o n. 
b) 
O bser ve t he s u bj ect f or at least 1 h o ur after st u d y dr u g a d mi nistrati o n. 
c) 
C ollect vit al si g ns j ust pri or t o disc har ge. 
If a n a p hyl axis is s us pecte d, a s a m ple of bl o o d s h o ul d be o bt ai ne d f or pl as m a hist a mi ne level a n d 
try pt ase wit hi n 1 – 2 h o urs of t h e o nset of sy m pt o ms. Als o, a n u nsc he d ule d A D A bl o o d s a m ple 
m ay b e o bt ai ne d if a n i m m u n o ge nicity-rel ate d A E is s us pecte d. 
1 3. 6  
D a y 4 3 ( ± 5) – D ose 4 
1) 
Pri or t o S C I njecti o n: 
a) 
Assess t he s u bject f or A E a n d S A E. 
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) 
Assess  
 c o m plia nce. 
d) Perf or m I G A, E A SI, 
 assess me nts. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 0 of 1 3 5 
C o nfi d e nti al  
e)
Ha ve s u bject c o m plete  
a n d  
 a n d 2 q uesti o ns o n t he  
 
q uesti o n naire.
f)
C ollect b o d y wei g ht (i n k g). 
g) 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. 
h)
Perf or m s y m pt o m- directe d p h ysical e xa m, as nee de d.
2) 
S C I njecti o n of St u d y Dr u g: 
a) E nter t h e visit i n t h e I R T a n d pre pare st u d y dr u g usi n g kit n u m ber(s) pr o vi de d b y t he 
I R T. See t h e P h ar mac y Ma n ual f or det aile d S C i njecti o n pre parati o ns. 
b) C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t h e start of t he S C i njecti o n. 
c) 
C ollect bl o o d f or C B C, c he mistr y, P K a n d A D A j ust pri or t o t he S C i njecti o n. 
d) 
A d mi nister S C i njecti o n i n t h e fr o nt of t he t hi g h. 
e) 
C ollect vit al si g ns 1 5 ( ± 5) mi n utes after st u d y dr u g a d mi nistrati o n. 
3) 
P ost- S C I njecti o n: 
a) 
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e S C i njecti o n. 
b) 
O bser ve t he s u bj ect f or at least 1 h o ur after st u d y dr u g a d mi nistrati o n.  
c)
C ollect vit al si g ns j ust pri or t o disc har ge.
If a n a p hyl axis is s us pecte d, a s a m ple of bl o o d s h o ul d be o bt ai ne d f or pl as m a hist a mi n e level a n d 
try pt ase wit hi n 1 – 2 h o urs of t h e o nset of sy m pt o ms. Als o, a n u nsc he d ule d A D A bl o o d s a m ple 
m ay b e o bt ai ne d if a n i m m u n o ge nicity-rel ate d A E is s us pecte d.
1 3. 7
D a y 5 7 ( ± 5) – D ose 5
1)
Pri or t o S C I njecti o n:
a)
Assess t he s u bject f or A E a n d S A E.
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)
Assess  
 c o m plia nce.
d)
C o m plete I G A, E A SI, 
assess m e nts.
e)
Ha ve s u bject c o m plete  
a n d  
 a n d 2 q uesti o ns o n t he  
 
q uesti o n naire.
f)
C ollect b o d y wei g ht (i n k g).


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 1 of 1 3 5 
C o nfi d e nti al  
g)
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.
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d. 
2)
S C I njecti o n of St u d y Dr u g:
a)
E nter t h e visit i n t h e I R T a n d pre pare st u d y dr u g usi n g t he kit n u m ber(s) pr o vi de d b y 
t he I R T. Se e t h e P h ar m ac y Ma n ual f or detaile d S C i njecti o n pre parati o ns. 
b)
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of t he S C i njecti o n.
c) 
C ollect bl o o d f or C B C, I g E, c he mistr y, a n d P K j ust pri or t o t he S C i njecti o n. 
d) 
A d mi nister S C i njecti o n i n t h e fr o nt of t he t hi g h. 
e) 
C ollect vit al si g ns 1 5 ( ± 5) mi n utes after st u d y dr u g a d mi nistrati o n.  
3) 
P ost- S C I njecti o n: 
a) 
C ollect bl o o d f or C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e S C i njecti o n. 
b) 
O bser ve t he s u bj ect f or at least 1 h o ur after t he e n d of t h e S C i njecti o n. 
c) 
C ollect vit al si g ns j ust pri or t o disc har ge. 
If a n a p hyl axis is s us pecte d, a s a m ple of bl o o d s h o ul d be o bt ai ne d f or pl as m a hist a mi ne level a n d 
try pt ase wit hi n 1 – 2 h o urs of t h e o nset of sy m pt o ms. Als o, a n u nsc he d ule d A D A bl o o d s a m ple 
m ay b e o bt ai ne d if a n i m m u n o ge nicity-rel ate d A E is s us pecte d.
1 3. 8  
D a y 7 1 ( ± 5) – D ose 6 
1) 
Pri or t o S C I njecti o n: 
a) 
Assess t he s u bject f or A E a n d S A E. 
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) 
Assess  
 c o m plia nce.
d) Perf or m I G A,  
 E A SI, a n d  
 assess m e nts.
e) 
Ha ve s u bject c o m plete  
a n d  
 a n d 2 q uesti o ns o n t he  
 
q uesti o n naire.
f)
C ollect b o d y wei g ht (i n k g). 
g) 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. 
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 2 of 1 3 5 
C o nfi d e nti al  
2)
S C I njecti o n of St u d y Dr u g:
a)
E nter t h e visit i n t h e I R T a n d pre pare st u d y dr u g usi n g t he kit n u m ber(s) pr o vi de d b y 
t he I R T. Se e t h e P h ar m ac y M a n ual f or detaile d S C i njecti o n pre parati o ns.
b)
C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t he start of t he S C i njecti o n.
c) 
C ollect bl o o d f or C B C, c he mistr y, a n d P K j ust pri or t o t he S C i njecti o n.
d) 
A d mi nister S C i njecti o n i n t h e fr o nt of t he t hi g h. 
e) 
C ollect vit al si g ns 1 5 ( ± 5) mi n utes after st u d y dr u g a d mi nistrati o n. 
3)
P ost- S C I njecti o n:
a)
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e S C i njecti o n.
b) 
O bser ve t he s u bj ect f or at least 1 h o ur after t he S C i njecti o n. 
c) 
C ollect vit al si g ns j ust pri or t o disc har ge. 
If a n a p hyl axis is s us pecte d, a s a m ple of bl o o d s h o ul d be o bt ai ne d f or pl as m a hist a mi ne level a n d 
try pt ase wit hi n 1 – 2 h o urs of t h e o nset of sy m pt o ms. Als o, a n u nsc he d ule d A D A bl o o d s a m ple 
m ay b e o bt ai ne d if a n i m m u n o ge nicity-rel ate d A E is s us pecte d.
1 3. 9  
D a y 8 5 ( ± 5) – D ose 7 
1) 
Pri or t o S C I njecti o n: 
a) 
Assess t he s u bject f or A E a n d S A E. 
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) 
Assess  
 c o m plia nce. 
d) Perf or m I G A, E A SI, 
 assess me nts.
e) 
Ha ve s u bject c o m plete  
a n d  
 a n d 2 q uesti o ns o n t he  
 
q uesti o n naire.
f)
C ollect b o d y wei g ht (i n k g). 
g) 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. 
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d. 
2) 
S C I njecti o n of St u d y Dr u g: 
a) E nter t h e visit i n t h e I R T a n d pre pare st u d y dr u g usi n g t he kit n u m ber(s) pr o vi de d b y 
t he I R T. Se e t h e P h ar m ac y Ma n ual f or detaile d S C i njecti o n pre parati o ns. 
b) C ollect vit al si g ns wit hi n 3 0 mi n utes pri or t o t h e start of t he S C i njecti o n.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 3 of 1 3 5 
C o nfi d e nti al  
c)
C ollect bl o o d f or C B C, I g E, c he mistr y, P K, a n d A D A j ust pri or t o t he S C i njecti o n.
d) 
A d mi nister S C i njecti o n i n t h e fr o nt of t he t hi g h. 
e)
C ollect vit al si g ns 1 5 ( ± 5) mi n utes after st u d y dr u g a d mi nistrati o n.
3)
P ost- S C I njecti o n:
a) 
C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e S C i njecti o n.
b)
O bser ve t he s u bj ect f or at least 1 h o ur after st u d y dr u g a d mi nistrati o n. 
c) 
C ollect vit al si g ns j ust pri or t o disc har ge. 
If a n a p hyl axis is s us pecte d, a s a m ple of bl o o d s h o ul d be o bt ai ne d f or pl as m a hist a mi ne level a n d 
try pt ase wit hi n 1 – 2 h o urs of t h e o nset of sy m pt o ms. Als o, a n u nsc he d ule d A D A bl o o d s a m ple 
m ay b e o bt ai ne d if a n i m m u n o ge nicity-rel ate d A E is s us pecte d.
1 3. 1 0  D a y 9 9 ( ± 5) or 1 4 D a ys P ost- D ose – F oll o w- u p Visit 1 
1) 
Assess t he s u bject f or A E a n d S A E. 
2) 
D oc u m e nt a n y c h a n ges t o c o nc o mita nt me dicati o ns. 
3) 
Assess  
 c o m plia nce. 
4) 
Perf or m I G A, E A SI, 
 assess m e nts. 
5) 
Ha ve s u bject c o m plete  
 a n d  
 t w o q u esti o ns o n t he  
 q uesti o n naire, 
a n d t he At o pic C o n diti o ns Q uesti o n naire. 
6) 
C oll ect b o d y wei g ht (i n k g). 
7) 
C oll ect uri ne f or uri nal ysis. 
8) 
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 nti al. 
9) 
C oll ect vital si g ns. 
1 0) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d. 
1 1) 
C ollect bl o o d f or C B C, c he mistr y, P K, a n d A D A.
1 2) 
C ollect bl o o d f or t otal ser u m I g E. 
1 3) If c o nse nt is o btai ne d, c ollect bi o ps y (a p plica ble f or select e d U S sites o nl y).
If t h e s u bject el ects t o recei v e O L E d osi n g, t h e O L E peri o d of t h e st u d y m a y be gi n after all 
Da y 9 9 assess me nts of t h e d o u ble- bli n d peri o d ha ve b ee n c o m plete d. T he st art of O L E d osi n g 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 4 of 1 3 5 
C o nfi d e nti al  
ma y be d ela y e d f or u p t o 7 da ys after c o m pleti o n of t he D a y 9 9 visit. T he s u bject is i n t he 
d o u ble- bli n d peri o d of t h e st u d y u ntil t he first O L E d ose of lire nteli m a b is a d mi nistere d.
1 3. 1 1
D a y 1 4 1 ( ± 5) or 5 6 D a ys P ost- D os e – F oll o w- u p Visit 2
1) 
Assess t he s u bject f or A E a n d S A E. 
2)
D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns.
3)
Assess  
 c o m plia nce.
4)
Perf or m I G A, E A SI, 
assess m e nts.
5)
Ha ve s u bject c o m plete  
a n d  
 a n d 2 q uesti o ns o n t he  
 q uesti o n naire.
6) 
C oll ect b o d y wei g ht (i n k g). 
7) 
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 nti al. 
8) 
C oll ect vital si g ns. 
9) 
Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d. 
1 0) 
C ollect bl o o d f or C B C, I g E, c he mistr y, a n d P K. 
1 3. 1 2  D a y 1 6 9 ( ± 5)/ E n d of St u d y or 8 4 D a ys P ost- D ose – F oll o w- u p Visit 3 
1) 
Assess t he s u bject f or A E a n d S A E. 
2) 
D oc u m e nt a n y c h a n ges t o c o nc o mita nt me dicati o ns. 
3) 
Assess  
 c o m plia nce. 
4)
Perf or m I G A, E A SI, 
 assess me nts.
5)
Ha ve s u bject c o m plete  
a n d  
 a n d 2 q uesti o ns o n t he  
 q uesti o n naire.
6)
C ollect b o d y wei g ht (i n k g).
7)
C ollect uri ne f or uri nal ysis.
8)
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.
9)
Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
1 0)
C ollect bl o o d f or C B C, c he mistr y, P K, a n d A D A.
1 1)
C ollect bl o o d f or t otal ser u m I g E.
1 2)
C ollect vit al si g ns.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 5 of 1 3 5 
C o nfi d e nti al  
F or E arl y Ter mi n ati o n ( E T): Perf or m t he visit 1 4, 5 6, or 8 4 ( ± 5) da ys aft er t h e last d ose of 
st u d y dr u g or pri or t o t his, if necess ar y, t o e ns ure c o m plia nce wit h t he visit. 
1 3. 1 3
E n d of St u d y Defi niti o n
T he e n d of t he d o u bl e- bli n d, place b o-c o ntr olle d peri o d of t h e st u d y is defi ne d as t he c o m pleti o n 
of t he last f oll o w- u p visit of t he last e nr olle d s u bject w h o elects n ot t o parti ci p ate i n t he O L E 
peri o d of t he st u d y. 
F or s u bjects electi n g t o e nter t h e O L E peri o d of t h e st u d y, t he e n d of t he O L E peri o d of t he st u d y 
is defi ne d as t he c o m pleti o n of t h e last f oll o w- u p visit f or t he l ast s u bject. 
T he e nr oll m e nt of t h e last s u bject i n t he d o u ble- bli n d peri o d of t he st u d y is a nti ci pate d t o occ ur
i n t h e first half of 2 0 2 3. T he last s u bject’s last f oll o w u p visit will be a p pr o xi matel y 2 4 wee ks 
after t he d ate of e nr oll m e nt if O L E is n ot electe d, or u p t o 3 8 wee ks after t h e date of e nr oll m e nt 
if t he O L E is elect e d. 
Please refer t o Secti o n 1 4. 1 2 f or t h e st u d y e n di n g pre m at urel y.  
1 4.
A d verse E v e nt R e p orti n g a n d D oc u me nt ati o n
1 4. 1
A d v erse E ve nts 
I n acc or da n ce wit h 2 1 C o de of Fe deral Re g ulati o n ( C F R) 3 1 2. 3 2( b) a n d I nter nati o nal 
C o nfere nce o n Har m o nizati o n (I C H) G ui d a nce E 2 A, a n A E is a n y u nt o war d me dical occ urre nce 
i n a cli nical i n vesti gati o n of a s u bject a d mi nistere d a p har mace uti cal pr o d u ct a n d t hat d oes n ot 
necessaril y ha ve a ca us al relati o ns hi p wit h t h e treat me nt. 
A n A E is t heref ore a n y u nfa v ora bl e a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or dis ease te m p orall y ass o ciate d wit h t h e 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 uct. A n u ne x p ect e d A E is o ne of a 
t y pe n ot i de ntifie d i n nat ure, se verit y, or fre q ue nc y i n t h e c urre nt I n v esti gat or’s Br oc h ure or of 
greater s e verit y or fre q u e nc y t h a 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 xa m ples of a n A E i n cl u de: 
Si g nifica nt w orse ni n g or e xacer 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 xa ms, vital si g ns, or la b orat or y tests. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 6 of 1 3 5 
C o nfi d e nti al  
T he f oll o wi n g e xa m ples are n ot c o nsi dere d A E:
 
Me dical or s ur gical pr oce d ure, alt h o u g h t he c o n diti o n lea di n g t o t he pr oce d ure is us uall y 
a n A E. 
 
A ntici pate d da y-t o- d a y fl u ct 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 baseli n e d oes n ot occ ur.
 
Si g ns or s y m pt o ms of t he dis or der bei n g st u die d u nless t he y bec o me m ore se vere or occ ur 
wit h greater fre q u e nc y t h a n occ urri n g at baseli ne.
All A E, w het her elicite d b y q uesti o ns fr o m st u d y staff, v ol u nteer e d, or n ot e d o n p h ysical 
e xa mi n ati 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 ass esse 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 t he first a d mi nistrati o n of st u d y dr u g i n t he d o u ble- bli n d 
peri o d of t he st u d y a n d e n di n g at t he ti me of st u d y c o m pleti o n or E T of t h e d o u ble- bli n d peri o d 
or t he O L E peri o d, w hic he ver is later. 
F or s u bjects p arti ci pati n g i n t he O L E peri o d, A E will be rec or d e d i n t he C R F of t h e A K 0 0 2- 0 1 8 
d o u ble- bli n d treat me nt p eri o d data bas e u p u ntil t h e first a d mi nistrati o n of lire nteli ma b i n t he 
O L E peri o d a n d rec or de d i n t he C R F of t h e A K 0 0 2- 0 1 8 O L E peri o d d ata base be gi n ni n g fr o m 
t he ti me of first a d mi nistrati o n of lire nteli ma b e n di n g at t h e ti me of st u d y c o m pleti o n or E T of 
t he O L E p eri o d.
1 4. 2
Seri o us A d verse E v e nts 
A S A E is defi ne d as a n A E t hat m eets t hat o ne of t h e f oll o wi n g criteria: 
 
Deat h 
 
A life-t hreate ni n g A E t hat places t h e s u bject at ris k of deat h at t h e ti me of t he e ve nt. It d oes 
n ot refer t o a n e ve nt t h at h y p ot 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 pacit y. 
 
A c o n ge nit al 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 d ere d a S A E w he n, bas e d o n a p pr o priate 
me dical j u d g me nt, t he y je o p ar diz e t he s u bject or re q uire i nter v e nti o n t o pre ve nt a n y of t h e 
o utc o mes liste d a b o ve. 
Seri o us a d verse e ve nts will b e assesse d a n d rec or de d be gi n ni n g after t he first a d mi nistrati o n of 
st u d y dr u g i n t h e d o u ble- bli n d peri o d a n d e n di n g at t he ti me of st u d y c o m pleti o n or E T of t h e 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 7 of 1 3 5 
C o nfi d e nti al  
d o u ble- bli n d peri o d or t h e O L E peri o d, w hic he ver is later. If t he S A E is relate d t o a scree ni n g 
pr oce d ure, it will b e ca pt ure d fr o m t he d ate of t he scree ni n g pr o ce d ure.  
1 4. 3
A d v erse E ve nts of S peci al I nterest 
A d vers e E v e nts of S pecial I nt erest ( A E SI) f or t his st u d y i n cl u de:  
Mali g na ncies c o nfir me d b y hist o pat h ol o gical re p ort. ( Mast cells a n d e osi n o p hils are part of 
t he n or mal i m m u ne res p o nse. B y decreasi n g t heir f u ncti o n, lire nteli m a b c o ul d t h e oreticall y 
i ncreas e t he ris k of m ali 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 beli e ve d 
t o be i n v ol ve d i n pr otecti n g t he b o d y fr o m parasitic i nfecti o ns. D ecreasi n g t h eir f u ncti o n 
c o ul d t he oreti call y i ncrease t he ris k of parasitic a n d o p p ort u nistic i nfecti o ns.)
 
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 v e cli nical la b orat or y test. 
 
I njecti o n-rel ate d reacti o ns a n d h y perse nsiti vit y reacti o ns, i ncl u di n g a na p h yla xis. 
A d vers e E v e nts of S pecial I nt erest will be ass esse d be gi n ni n g after t he ti m e of first 
a d mi nistrati o n of st u d y dr u g a n d e n di n g at t h e ti m e of st u d y c o m pleti o n or E T of t he d o u ble-
bli n d peri o d or t h e O L E peri o d, w hic he v er is later. 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 b e rec or de d i n t h e A E e C R F a n d desi g nate d as a n “ A E of 
s pecial i nterest.” 
1 4. 4
I njecti o n- Rel ate d Re acti o ns
All A E c o nsi dere d b y t h e I n v esti gat or t o be rel ate d t o t h e 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 h e S C i njecti o n of st u d y dr u g s h o ul d be ca pt ure d as 1 I R R. 
C o m m o n s y m pt o ms of I R R ma y i ncl u de b ut are n ot e xcl usi ve t o: 
Fl us hi n g
Na us ea
C hills
V o miti n g
 
Bac k or a b d o mi nal pai n 
 
S w eati n g 
 
C hest dis c o mf ort or ti g ht ness 
 
Fe ver 
 
Dizzi ness 
 
Urticaria 
 
S h ort ness of breat h 
 
Pr urit us 
 
Hea d ac he 
 
Br o nc h os pas m 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 8 of 1 3 5 
C o nfi d e nti al  
 
H y p ote nsi o n or h y perte nsi o n 
All s y m pt o ms e x perie nce d b y a s u bject d uri n g a n I R R will be liste d i n t he e C R F u n der 1 I R R, 
u nless t he I n vesti gat or belie ves a s y m pt o m is n ot part of t he I R R, i n w hic h c ase 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 ti me of t h e I R R will be ca pt ure d as t h e e n d ti me of t h e last s y m pt o m.  
1 4. 5
I njecti o n Site R e acti o ns
All A E c o nsi dere d b y t h e I n v esti gat or t o be rel ate d t o t he S C a d mi nistr ati o n of t he bi ol o gical 
s u bsta nce at t h e i njecti o n site  a n d occ urri n g wit hi n 2 4 h o urs of t he start of t he i njecti o n s h o ul d 
be ca pt ure d as o ne i njecti o n sit e reacti o n (I S R). 
C o m m o n s y m pt o ms of I S R i ncl u de, b ut are n ot e xcl usi v e t o: 
 
Re d ness at t h e i njecti o n sit e 
 
Itc hi n g at t he i njecti o n site 
 
Pai n at t he i njecti o n site 
 
S w elli n g at t h e i njecti o n site ( be y o n d t he b u m p ca use d b y t he v ol u me of dr u g i njecte d 
u n der t h e s ki n) 
 
Br uisi n g at t h e i njecti o n site 
 
B ur ni n g at t he i njecti o n site 
All s y m pt o ms e x perie nce d b y t he s u bject d uri n g a n I S R will be liste d i n t he e C R F u n der 1 I S 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 S R, i n w hic h c ase it will be 
rec or d e d se paratel y. T h e start ti me of t he I S R will be ca pt ure d as t he start ti me of t h e first 
s y m pt o m, a n d t he e n d ti me of t h e I S R will be ca pt ure d as t h e e n d ti me of t h e last s y m pt o m. 
1 4. 6  
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 tr eate 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 m e 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 m es d uri n g t h e 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 E of s us pecte d 
a na p h yla xis will be e val u ate d usi n g Sa m ps o n’s Criteria f or A n a p h yla xis ( A p pe n di x 9) . T he 
assess me nt of a n A E will be d o ne p urs ua nt t o defi niti o ns set f ort h b y I C H G o o d Cli nical Practi ce 
( G C P) g ui deli nes a n d a p plica ble re g ulat or y re q uire me nts.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 8 9 of 1 3 5 
C o nfi d e nti al  
If a s u bject e x peri e nces si g ns or s y m pt o ms of a na p h yla xis, t he y s h o ul d be treate d wit h sta n dar d 
of care, s uc h as di p h e 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 h er 
s u p p orti ve meas ures al o n g wit h cess ati o n of t h e S C i njecti o n. 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 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 n e d if a n i m m u n o ge nicit y-relate d A E is 
s us pecte d.
1 4. 7
E v al u ati n g A d verse E ve nts a n d Seri o us A d verse E v e nts 
1 4. 7. 1
Est a blis hi n g Di a g n osis 
W he ne v er p ossi ble, dia g n oses s h o ul d be gi ve n w he n si g ns a n d s y m pt o ms are d ue t o a c o m m o n 
eti ol o g y (e. g., d ys uria, uri nar y 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 E. T he I n vesti gat or ( or q ualifie d S u bi n 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 ( Ta ble 3, T a ble 4, a n d Ta ble 5) a n d is res p o nsi ble f or 
e ns uri n g t his i nf or mati o n is rec or de d i n t he s o urce d oc u m e ntati o n. 
1 4. 7. 2  
Assess me nt of I nte nsit y 
I n v esti gat ors will use t heir cli nical j u d g me nt as w ell as t he g ui deli n es l ai d o ut i n t he N CI 
C T C A E ( versi o n 5. 0 or m ost c urre nt versi o n) t a bles ( Ta ble 3 a n d  A p pe n di x 8) t o assess t he 
i nte nsit y of eac h A E a n d S A E. 
T a bl e 3  
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 ostic o bser v ati o ns o nl y; i nter ve nti o n 
n ot i n dicate d. 
2  
M o d erate; mi ni mal, l o cal, or n o ni n vasi v e 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 acti vities of d ail y li vi n g ( A D L). 
3  
Se v ere 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 g e nt i nter ve nti o n i n dicate d. 
5  
D eat h relate d t o A E. 
* C T C A E v. 5. 0: Gra de refers t o t h e se v erit y of t h e A E. T h e C T C A E dis pla ys Gra des 1 – 5 wit h u ni q u e cli nical 
d escri pti o ns of se verit y f or eac h A E b ase d o n t his g e neral g ui d eli ne. 
T he ter m “se v ere” is a m eas ure of i nte nsit y, a n d a se vere A E is n ot necess aril y a S A E. W he n t he 
i nte nsit y of a n A E c ha n g es wit hi n t he sa me da y, t he ma xi m u m se verit y f or t he e ve nt s h o ul d be 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 0 of 1 3 5 
C o nfi d e nti al  
e ntere d i nt o t he 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 g es s h o ul d 
be rec or de d s e paratel y (i. e., as ha vi n g disti nct o nset dates). 
1 4. 7. 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 4 t o ass ess 
t he relati o ns hi p bet wee n st u d y dr u g a n d A E. 
T a bl e 4  
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 h ere is clear e vi de nce t h at t he e ve nt is relate d t o t h e use of st u d y dr u g (e. g., c o nfir mati o n 
b y p ositi v e re-c halle n ge test, if p ossi ble). A n ot h er eti ol o g y is c o nsi d era bl y less li k el y. 
P ossi ble  
T h e e v e nt ca n n ot b e e x plai n e d b y t h e s u bject’s m e dical c o n diti o n, c o nc o mita nt t h era p y, or 
ot h er ca uses, a n d t h ere is a pla usi ble te m p oral relati o ns hi p bet wee n t he e v e nt a n d st u d y dr u g 
a d mi nistrati o n.  
U nli k el y/ Re m ote 
A n e ve nt f or w hic h a n alter nati v e e x pla nati o n is m ore li k el y (e. g., c o n c o mita nt me dicati o ns 
or o n g oi n g m e dical c o n diti o ns) or t h e 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 g ests t h at a ca usal relati o ns hi p is u nli k el y. ( F or re p orti n g p ur p oses, 
U nli k el y/ Re m ote will be gr o u pe d t o get h er wit h N ot Relate d.)  
N ot Relate d  
T he e v e nt ca n b e rea dil y e x plai n e d b y t h e s u bject’s u n derl yi n g m e dical c o n diti o n, 
c o n c o mita nt t h era p y, or ot h er ca uses, a n d t h eref ore, t h e I n vesti gat or b elie v es n o relati o ns hi p 
e xists bet wee n t he e v e nt a n d st u d y dr u g.  
1 4. 7. 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 5 t o assess 
t he relati o ns hi p bet wee n st u d y pr oce d ure a n d A E. Assess m e nt of ca us alit y t o st u d y pr oce d ure 
s h o ul d i n cl u de ca usalit y t o s uc h ite ms as bl o o d dra w (as a p pr o priate), or ot h er.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 1 of 1 3 5 
C o nfi d e nti al  
T a bl e 5  
A d verse E ve nt R el ati o ns hi p t o St u d y P r oce d ure
Rel ati o ns hi p t o 
St u d y P r oce d ure
C o m me nt 
Relate d  
T h ere is clear e vi de nce t h at t he e ve nt is relate d t o a st u d y pr o ce d ure. 
P ossi ble  
T h e e v e nt ca n n ot b e e x plai n e d b y t h e s u bject’s m e dical c o n diti o n, c o nc o mita nt t h era p y, or 
ot h er ca uses, a n d t h ere is a pla usi ble te m p oral relati o ns hi p bet wee n t he e v e nt a n d a st u d y 
pr o ce d ure.  
U nli k el y/ Re m ote
A n e v e nt f or w hic h a n alter n ati v e e x pla nati o n is m ore li k el y (e. g., c o n c o mita nt m e dicati o ns 
or o n g oi n g m e dical c o n diti o ns) or t h e 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 g ests 
t h at a ca usal relati o ns hi p is u nli k el y ( F or re p orti n g p ur p oses, U nli kel y/ Re m ote will be 
gr o u p e d t o get h er wit h N ot Relate d).  
N ot Relate d  
T he e v e nt ca n b e rea dil y e x plai n e d b y t h e s u bject’s u n derl yi n g m e dical c o n diti o n, 
c o n c o mita nt t h era p y, or ot h er ca uses, a n d t h eref ore, t h e I n vesti gat or b elie v es n o relati o ns hi p 
e xists bet wee n t he e v e nt a n d a st u d y pr oce d ure.  
1 4. 7. 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 cate g orize d as n o ne, st u d y dr u g per 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 parti ci pati o n will be cate g orize d as n o ne, wit h dra wal fr o m 
st u d y partici pati o n, or ot her (s pecif y).  
Acti o n ta ke n wit h res p ect t o treat m e nt of a n A E will b e cate g orize d as n o ne, c o nc o mit a nt 
me dicati o n, c o nc o mita nt pr oce d ure, or ot h er (s pecif y).  
1 4. 7. 6  
Assess me nt of O utc o me 
E ve nt o utc o me at res ol uti o n or ti me of last f oll o w- u p will be rec or de d as: rec o vere d, rec o veri n g, 
n ot rec o vere d, rec o vere d wit h se q u elae, f atal, or u n k n o w n.  
1 4. 8  
A d verse E ve nt R e p o rti n g Pr oce d ures  
1 4. 8. 1  
All A d verse E v e nts 
A n y cli nicall y si g nifica nt A E t h at is o n g oi n g at t he ti me of st u d y c o m pleti o n or E T will be 
f oll o we d b y t he I n vesti g at or u ntil e ve nt res ol uti o n, t he A E is ot her wise e x pl ai ne d, n ot c o nsi dere d 
cli nicall y si g nifica nt b y t he I n vesti gat or, or t h e s u bject is l ost t o f oll o w- u p. 
All A E i de ntifie d, w het h er 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 first a d mi nistrati o n of st u d y dr u g i n t he d o u ble- bli n d peri o d of t he st u d y a n d e n di n g at 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 2 of 1 3 5 
C o nfi d e nti al  
t he ti me of st u d y c o m pleti o n or E T of t he d o u ble- bli n d peri o d or t h e O L E p eri o d, w hic he v er is 
later. S eri o us a d verse e ve nts c o nsi dere d relate d t o scree ni n g pr o ce d ures will be rec or de d i n t h e 
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 ( versi o n 
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 E ( A p pe n di x 8).
1 4. 8. 2  
Seri o us A d v erse E ve nt Re p orti n g  
I n t he e ve nt of a n y S A E re p orte d or o bs er v e d d uri n g t h e st u d y, w het her or n ot attri b uta ble t o t he 
st u d y dr u g, site pers o n nel m ust re p ort it i m me diatel y ( wit hi n 2 4 h o urs of b ec o mi n g a w are of 
t he S A E) b y fa x or e mail t o t h e S p o ns or, All a k os I nc.  
T he 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 sit e t o assist i n c ollecti n g, 
or ga nizi n g, a n d re p orti n g S A E, a n d f or ms m ust be c o m plete d wit h as m u c h i nf or mati o n as is 
a vaila ble a n d s h o ul d be s u b mitte d t o t h e S p o ns or wit hi n 2 4 h o urs of b ec o mi n g a ware of t he 
S A E. Seri o us a d verse e v e nts m ust als o be rec or de d o n t h e A E e C R F a n d d esi g nate d as “s eri 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 h e 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 h e ca usalit y is use d t o deter mi ne t h e ti mi n g of 
re g ulat or y re p orti n g re q uire me nts. If t he I n v esti gat or or desi g nee is n ot a v aila ble t o si g n t h e S A E 
re p ort o n i nitial s u b missi o n, t he y s h o ul d be c o ntacte d b y tele p h o ne a n d t h eir 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 
ma y c ha n ge t h eir ca us alit y ass ess me nt base 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 ort f or m. All eff orts will be ma de t o o btai n acc urate a n d c o m plete me dical rec or ds f or 
t he S A E. All eff orts t o o btai n i nf or mati o n s h o ul d be d oc u me nte d i n t he s u bject’s s o urce 
d oc u me nts. 
T he site will n otif y t he I n de pe n de nt Et hics C o m mittee (I E C)/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 he I n vesti gat or or d esi 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 h e 
s u bject will be as k e d t o ret ur n t o t h e st u d y site f or f urt her f oll o w u p. If t he c o n diti o n is still 
o n g oi n g at t he ti me t he s u bject e xits t he st u d y, e ver y eff ort will be ma de t o c o nti n ue t o f oll o w- u p 
wit h t h e s u bject f or a reas o na bl e 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 h ere 
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 
a vaila ble, s uc h as h os pital disc har g e n otes a n d s u bj ect me dical rec or ds, t he I n v esti gat or will be 
n otifie d a n d pr o vi d e d wit h all rele va nt i nf or mati o n.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 3 of 1 3 5 
C o nfi d e nti al  
All S A E 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 h at h a ve n ot res ol v e d o n 
disc o nti n uati o n of t he s u bject’s p artici 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 h e 
f oll o wi n g occ urs: 
 
T he e ve nt res ol ves.  
 
T he e ve nt sta bilizes. 
T he e ve nt ret ur ns t o baseli ne if a baseli ne v al ue is a vaila ble. 
T he e ve nt ca n be attri b ute d t o a ge nts ot her t h a n t h e i n vesti g ati 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 diti o nal i nf or mati o n, l ost t o f oll o w- u p after de m o nstrati o n 
of d ue dili ge nce wit h f oll o w- u p eff orts). 
Seri o us A E m ust be re p orte d wit hi n 2 4 h o urs t o:  
  
Fa x: 
+ 1- 8 8 8- 2 3 7- 7 4 7 5 
  
E mail: 
S A E @all a k os.c o m 
1 4. 8. 3  
Pre g n a nc y Re p orti n g 
Pre g na ncies are ca pt ure d if t he y occ ur i n fe male s u bjects or i n t he se x ual p art 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 a n d e n di n g at t he 
ti m e of st u d y c o m pleti o n or E T of t he d o u ble- bli n d peri o d or t h e O L E p eri o d, w hi c he ver is later.  
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 m e diatel y if t he y b ec o me pre g na nt d uri n g t he st u d y. Male s u bjects m ust i nf or m t he 
I n v esti gat or i m me diatel y if t heir part ner bec o m es pre g n a nt d uri n g t h e 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 All a k os wit hi n 2 4 h o urs of bec o mi n g a ware of it 
usi n g t h e pr o vi de d pre g n a nc y re p orti n g f or ms. Fe male s u bjects 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 nc y will n ot be c o nsi d ere d a n A E or 
S A E, b ut all pre g na ncies i n s u bjects w h o rec ei ve d lire nteli ma b will be f oll o we d t hr o u g h t er m. 
F or male s u bjects wit h fe male p art n ers w h o bec o m e pre g na nt, t h e site will as k t he fat h er (t he 
st u d y s u bject) t o pr o vi de i nf or mati o n a b o ut t he o utc o m e of t he pre g na n c y a n d i nf or mati o n a b o ut 
t he ba b y. If d etaile d healt h i nf or mati o n a b o ut t he m ot h er is re q ueste d b y Alla k os, a Pre g n a nt 
Part ner I nf or mati o n Release F or m will be pr o vi de d t o t he site f or t h e m ot her t o si g n.
A n y c o n ge nit al 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 
lire nteli ma b will be re p orte d as a S A E. If t h e s u bject recei v e d lire nteli ma b, t he o utc o me of a n y 
pre g n a nc y a n d t he prese nce or a bs e nce of a n y c o n ge nit al a b n or malit y will be rec or de d i n t he 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 4 of 1 3 5 
C o nfi d e nti al  
s o urce d oc u m e ntati o n a n d re p orte d t o t he Me di cal M o nit or a n d S p o ns or via t he pre g na n c y 
re p orti n g f or m.  
1 4. 8. 4
A E SI Re p orti n g
Be gi n ni n g fr o m t he ti me of first S C i njecti o n of st u d y dr u g a n d e n di n g at t he ti me of st u d y 
c o m pleti o n or E T of t h e d o u ble- bli n d peri o d or t h e O L E peri o d, w hic he ver is later, a n y ne w 
A E SI ( or ne w i nf or mati o n rel ate d t o a pre vi o usl y re p orte d A E SI) m ust be rec or de d i n t he A E 
e C R F a n d desi g nate d as a n “ A E of s p ecial i nterest.” 
F or s u bjects p arti ci pati n g i n t he O L E peri o d, A E SI will be assesse d a n d rec or de d i n t he C R F of 
t he A K 0 0 2- 0 1 8 d o u ble- bli n d treat m e nt peri o d data base u p u ntil t he st art of t he first O L E 
i njecti o n after t h e Da y 9 9 visit a n d rec or de d i n t he C R F of t he A K 0 0 2- 0 1 8 O L E peri o d data b ase 
be gi n ni n g fr o m t he start of t h e first O L E i njecti o n after t h e D a y 9 9 visit.
A n A E SI t h at als o q ualifi es as a S A E ( p er Secti o n 1 4. 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 4. 8. 2.  A d vers e e ve nts of s peci al i nterest t hat are als o S A E m ust be 
rec or d e d i n t he A E e C R F a n d desi g nate d as b ot h “seri o us” a n d as a n “ A E 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 orte d t o t he 
S p o ns or wit hi n 2 4 h o urs of site a ware ness. 
1 4. 9
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 ber a n d/ or e mail 
a d dress bel o w t o re p ort me dical c o ncer ns or f or q uesti o ns re g ar di n g safet y. 
All a k os Me dic al M o nit or
All a k os B ac k u p Me dic al M o nit or
 
, M D 
, M D 
  
P h o ne: 
 
P h o ne: 
 
E mail: 
E mail: 
 
Me dic al M o nit or f o r Ger m a n y
, M D, P h D 
  
P h o ne: 
 
E mail:
 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 5 of 1 3 5 
C o nfi d e nti al  
1 4. 1 0
I n d e pe n de nt D at a M o nit ori n g C o m mittee
A n i n de pe n de nt D ata 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 (as per t he i D M C c harter) 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 necessitate d b y data a n d/ or s afet y re vie ws.  
1 4. 1 1
St u d y Wit h dr a w al Criteri a
A s u bject’s partici p ati o n i n t h e st u d y will be disc o nti n ue d i n t he e ve nt t h at:
Occ urre n ce of a n e xcl usi o n criteri o n, w hic h is cli nicall y rel e va nt a n d affects t h e 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/
L i n s u bjects w h o e ntere d t h e st u d y wit h 
e osi n o p hil le vels > 1 5 0 0/ L a n d w h os e e osi n o p hil c o u nts were i nitiall y s u p presse d after 
st u d y dr u g, as assesse d b y t he S afet y M o nit or, m a y be wit h dra w n fr o m t he st u d y at t h e 
i nstr ucti o n of t h e Me dical M o nit or. 
 
Ser u m tra nsa mi n ases ( 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 re peat) wit h o ut a n alter nati ve e x pl a 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 orse ni n g of s y m pt o ms felt b y t he I n v esti gat or t o be p ote ntiall y rel ate d t o h e patic 
i nfla m mati o n, s uc h as fati g ue, na usea, v o miti n g, ri g ht u p per q ua dra nt pai n or te n der n ess, 
fe ver, a n d ras h. 
1 4. 1 2  St u d y St o p pi n g R ules 
T he st u d y ma y be dis c o nti n ue d pre mat urel y i n t h e 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 m e nt.  
 
Ne w i nf or mati o n le a 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 d ecisi o n t hat c o nti n uati o n of t he st u d y is u nj ustifia ble f or me dical or et hical 
reas o ns.  
 
Disc o nti n uati o n of de vel o p me nt of t he S p o ns or’s st u d y dr u g.  
 
A p pr o val of t he n ati o nal c o m pete nt a ut h orit y (i.e. Pa ul- E hrlic h-I nstit ut or P EI) or t he 
Fa v ora bl e O pi ni o n/ A p pr o val of I E C/I R B f or t h e c o n d uct of t he cli nical trial is wit h dra w n. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 6 of 1 3 5 
C o nfi d e nti al  
 
T he re q uir e d m o dificati o n of t he m a xi m u m i ns ure d s u m is n ot p ossi ble f oll o wi n g a
ne gati v e c h a n ge i n t he assess m e nt of t h e be nefit-ris k rati o, if a p pli ca ble (i.e., f or Ger ma n y) 
Healt h A ut h orities a n d I E C/I R B will be i nf or me d a b o ut t he disc o nti n uati o n of t he st u d y i n 
acc or d a nce wit h a p plica ble re g ulati o ns. T he st u d y 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. 
St u d y st o p pi n g f or a n i n di vi d ual site or i n vesti gat or ma y occ ur i n t he e ve nt of n o nc o m plia nce 
wit h t h e pr ot oc ol or la pse of g o o d cli nical practice. 
1 5.
Disc o nti n u ati o n a n d R e pl a ce me nt of S u bjects
1 5. 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 6 9 visit will be cate g orize d as ha vi n g 
c o m plete d t he d o u ble- bli n d peri o d of t h e st u d y. 
A s u bject w h o c o m pletes visits t hr o u g h t he Da y 9 9 visit a n d e nters t he O L E peri o d of t h e st u d y 
will b e cate g orize d as h a vi n g c o m plete d t he d o u ble- bli n d peri o d of t he st u d y. 
A s u bject w h o c o m pletes visits t hr o u g h t he O L E Da y 1 6 9 visit will be cate g orize d as ha vi n g 
c o m plete d t he O L E p eri o d of t h e st u d y. 
T he st u d y is c o nsi dere d c o m plete d w he n t he last s u bject c o m pletes t he l ast st u d y visit. 
1 5. 2  
E arl y Disc o nti n u ati o n of St u d y Dr u g  
A s u bject m a 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 g at 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 m e nt disc o nti n uati o n: 
 
S u bject wit h dra ws c o nse nt.  
 
A n A E t hat i n t he o pi ni o n of t he I n vesti gat or res ults i n it bei n g i n t he best i nterest of t he 
s u bject t o disc o nti n ue st u d y treat m e nt.  
Pr ot oc ol de viati o n re q uiri n g disc o nti n uati o n of st u d y treat m e nt.  
 
Partici pati o n i n a n y ot her st u d y d uri n g t he d urati o n of t his st u d y.  
 
Use of a n o n- per mitte d c o nc o mita nt dr u g, w hic h ma y a d vers el y affect data i nter pretati o n i n 
t he o pi ni o n of t he Me dical M o nit or. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 7 of 1 3 5 
C o nfi d e nti al  
 
L oss of a bilit y t o freel 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 
or treat m e 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 h e a b n or mal para m eter 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 m e 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 1 2- wee k f oll o w- u p peri o d i n Ta ble 1,
if p ossi ble.  
Reas o na ble atte m pts will be ma de b y t h e I n v esti g at or t o pr o vi de reas o ns f or s u bject wit h dra wals. 
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 urce d o c u me nts.  
1 6.
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 n es t h e st atistical met h o ds t o be use d f or t he a nal ysis of t he data fr o m t he st u d y. 
A se parate S A P, w hic h m ust be d oc u me nte d as c o m plete d pri or t o u n bli n di n g t he st u d y, will 
descri b e d ata h a n dli n g a n d statisti cal t ec h ni q ues i n f ull detail.  
U nless s pecifie d ot her wise, baseli ne will be defi ne d as t h e last wee k of scree ni n g bef ore t he first 
S C i njecti o n of st u d y dr u g. All s u bject data will be liste d. W he n a p pr o priat e, s u m m ar y st atistics 
of n u m ber of n o n- missi n g val ues, mea n, me di a n, sta n dar d de viati o n, mi ni m u m, a n d ma xi m u m 
will b e 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 de n ce i nter v als ( CI) will be pr o vi d e d 
f or t h e m ea n a n d pr o p orti o n. N o f or mal statisti cal i nfere n ces will be ma d e f or safet y para meters.  
1 6. 1
S a m ple Size
A p pr o xi matel y 1 3 0 e val u a ble s u bjects wit h m o derate-t o-se v ere A D will be e nr olle d. It is 
h y p ot hesize d t hat t h e per ce nta ge of s u bjects w h o ac hie ve E A SI- 7 5 at Wee k 1 4 are 4 4 % f or 
lire nteli ma b a n d 1 5 % f or place b o. T o det ect t he treat m e nt differe nce of 2 9 %, t he n u m ber of 
s u bjects re q uire d f or 9 0 % p o wer is 5 5. H o w e ver, t o acc o u nt f or 1 0 % dr o p o ut rate, t he sa m ple 
size will be i n crease d t o 6 5 per treat me nt gr o u p. 
E nr oll me nt will be m o nit ore d t o li mit t he i m pact of ra n d o mi zi n g a dis pr o p orti o natel y lar ge 
n u m ber of s u bjects wit h a n E A SI s c ore i n t he l o w er ra n g e, reflecti n g m ore m o derate disease o nl y 
(i.e., E A SI sc ore < 2 2). T his will als o pr o vi de a s u bject p o p ulati o n wit h a f ull ra n g e of E A SI 
sc ores c o nsiste nt wit h t he i nte nt t o st u d y lire nt eli m a b i n m o derate-t o-s e vere A D dis ease.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 8 of 1 3 5 
C o nfi d e nti al  
1 6. 2
A n al ysis P o p ul ati o ns
T he S afet y p o p ul ati o n  is defi ne d as all s u bje cts w h o are ra n d o mi ze d a n d ha ve recei ve d at least 
1 S C i njecti o n of t h e st u d y dr u g. 
T he pri mar y efficac y a nal ysis p o p ulati o n is t he m o difie d I nte nt-t o- Tre at ( mI T T) p o p ul ati o n , 
defi ne d as all ra n d o mize d s u bjects w h o ha ve recei ve d at least 1 S C i njecti o n of st u d y dr u g a n d
ha d n o maj or pr ot oc ol vi olati o ns base d o n ke y i ncl usi o n a n d e xcl usi o n criteria defi ni n g t he 
p o p ulati o n of i nterest (i.e., defi ne d as n ot meeti n g a n y of t he k e y i n cl usi o n crit eria n u m ber 3, 4, 
6, 7, 8 or meeti n g e xcl usi o n criteria n u m ber 8 i n t his st u d y).
T he sec o n d ar y efficac y a nal ysis p o p ulati o n is t h e Per Pr ot oc ol ( P P) p o p ul ati o n , defi ne d as 
mI T T s u bjects w h o ha ve recei v e d all 7 i njecti o ns of st u d y dr u g a n d di d n ot ha ve maj or pr ot o c ol 
vi olati o ns p ossi bl y i nterferi n g wit h i nter pretati o n of efficac y a n d safet y fi n di n gs.  
T he mI T T p o p ulati o n will be use d f or all effic ac y a nal ysis. T he P P p o p ulati o n will be use d f or 
t he pri mar y e n d p oi nt a n d select sec o n d ar y e n d p oi nt a nal yses t o e val u ate t he r o b ust ness of t h e 
effic ac y fi n di n gs. T he Safet y p o p ulati o n will be use d f or all safet y a nal ysis. 
T he st u d y statisti cia 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 xcl u de d fr o m t he P P p o p ulati o n a nal ysis.  
1 6. 3  
S u bject Dis p ositi o n 
S u bject dis p ositi o n a n d reas o n f or earl y disc o nti n uati o n will be ta b ulate d. S u bject de m o gra p hics, 
baseli n e c haracteristi cs, a n d treat m e nt e x p os ure will be s u m marize d. 
1 6. 4  
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 de m o gra p hic a n d baseli ne v aria bles will be s u m m arize d: 
 
De m o gra p hics 
 
Me dical hist or y 
 
C o m plete p h ysical e xa 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
Neit her t he s u bject’s i nitials n or t h e f ull date of birt h will b e d oc u me nte d i n t he C R F or i n t he 
q uesti o n naires.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa g e 9 9 of 1 3 5 
C o nfi d e nti al  
1 6. 5
St u d y Dr u g E x p os ure
N u m ber a n d p erce nt ( n a n d %) of s u bjects w h o h a ve recei ve d 1, 2, 3, 4, 5, 6, or 7 S C i njecti o ns
will b e prese nte d. 
1 6. 6  
Effic ac y A n al ysis 
1 6. 6. 1  
Pri m ar y Effic ac y E n d p oi nt A n al ysis 
F or all efficac y v ari a bles, t he a nal ysis will b e c o m paris o n of lire nteli ma b S C a n d t h e place b o 
treat me nt gr o u ps. T he f oll o wi n g n ull a n d alter nati ve h y p ot heses f or t h e pri m ar y e n d p oi nt will be 
teste d f or lire nteli ma b S C gr o u p a n d t he place b o gr o u p:
H 0: N o treat me nt differe nce bet w ee n lire nt eli m a b S C a n d place b o.
H 1: T here is a treat m e nt differe n ce b et wee n lire nt eli m a b S C a n d place b o. 
Baseli ne disease se v erit y i n de x [ m o derate (I G A = 3) a n d se vere (I G A = 4)] a n d pri or bi ol o gic 
e x perie n ce ( bi ol o gic- naï ve a n d bi ol o gic-e x p os e d) will b e t he 2 stratificati o n fact ors f or s u bject 
ra n d o mizati o n a n d will b e acc o u nte d f or i n t he statisti cal m o deli n g f or effic ac y. I n a d diti o n, if it 
is e vi de nt t hat t he pri mar y e n d p oi nt is c o nf o u n de d b y st u d y e ntr y c haracteristi cs [e. g., t he 
met h o d of I G A a n d/ or E A SI sc ore assess me nt b y A D s pecialist ( defi ne d as t he PI a n d or S u b-I 
bei n g eit her a n aller gist, i m m u n ol o gist or der mat ol o gist) as c o m p are d t o n o n- A D s peci alist, 
c ha n ge i n perce nt B S A great er t h a n 2 0 % at t h e e n d of t he L ea d-i n P h ase ( Da y - 1 4 t o Da y - 8) 
c o m pare d t o t he e n d of t he B aseli ne P hase ( Da y - 7 t o Da y - 1)), t h e n t he pri m ar y efficac y 
a nal ysis will be c o n d ucte d a dj usti n g f or t he effects of t h e bac k gr o u n d c haracteristi cs.  
T he pri mar y res p o n der e n d p oi nt will be a nal yze d usi n g t he C oc hra n- Ma ntel- Hae nszel test 
a dj uste d b y baseli ne disease se verit y i n de x [ m o derate (I G A = 3) a n d se vere (I G A = 4)], pri or 
bi ol o gic e x perie nce ( bi ol o gic- n aï ve a n d bi ol o gic-e x p ose d), a n d c o u ntr y ( U S A a n d Ger ma n y) at 
Wee k 1 4. T h e Ma ntel- Fl eiss ( M F) criteri o n will be perf or me d, a n d if it is n ot met w hile usi n g t he 
o pti o n C M H ( M F) i n S A S pr oce d ure P R O C F R E Q, a nal yses i ncl u di n g eac h fact or se paratel y i n 
C M H test will be c o n d ucte d. S h o ul d ass u m pti o n per t he M F criteri o n n ot b e satisfie d, t he 
c o m paris o n will be base d o n a Fis her’s e xa ct test after c olla psi n g acr oss le v els of t h e 
stratificati o n fact or a n d c o u ntr y. 
F or t he a nal ysis descri be d a b o ve, s u bjects w h o pre mat urel y dis c o nti n ue t h e ra n d o mize d 
treat me nt or i niti ate a n y treat me nt a dj ust me nts (e. g., use of pr o hi bite d/resc ue me dicati o n/resc ue 
treat me nt f or A D s y m pt o ms) will be ha n dle d as des cri b e d bel o w: 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 0 of 1 3 5 
C o nfi d e nti al  
 
If a s u bject wit h dra ws fr o m t h e st u d y, t his s u bject will be c o u nte d as a n o n-res p o n der f or 
t he ti me p oi nts after wit h dra w al. 
 
T o acc o u nt f or t h e i m pact of pr o hi bite d/resc ue m e dicati o n/resc ue treat me nt f or A D 
s y m pt o ms o n t he efficac y effect: if resc u e me dicati o n/resc ue treat m e nt f or A D s y m pt o ms is 
use d, t he s u bject will be s pecifie d as a n o n-res p o n d er fr o m t he ti me t he resc ue 
me dicati o n/resc ue treat m e nt is use d. 
 
If t h e s u bject has t h e missi n g val ue at Wee k 1 4, it will be c o u nte d as a n o n-res p o n der at 
Wee k 1 4.
T he pri mar y efficac y a nal ysis will b e perf or me d o n mI T T p o p ulati o n, as w ell as P P p o p ulati o n 
as a s u p p orti n g a nal ysis. I n a d diti o n, f or c o m plete ness p ur p oses, res ults i ncl u di n g all s u bjects 
a n d e xcl u di n g t h e s u bjects w h o ha d maj or pr ot o c ol de viati o ns o n t h e basis of ke y i ncl usi o n a n d 
e xcl usi o n crit eria d efi ni n g t he p o p ulati o n of i nterest will be prese nte d. T he differe n ces b et wee n 
t hese res ults will be n ote d, a n d t he i m pact of s uc h differe nces will be disc usse d i n t he cli nical 
st u d y re p ort.
1 6. 6. 2  
Sec o n d ar y Effic ac y E n d p oi nt A n al ysis
T he bi nar y sec o n dar y efficac y e n d p oi nt will be a n al yze d usi n g t he sa me a p pr oac hes as t hat are 
use d f or t he a nal ysis of t h e pri mar y e n d p oi nt. 
Mi xe d M o del f or Re peate d Meas ures ( M M R M) a n al yses will b e perf or me d o n c o nti n u o us 
e n d p oi nts t o miti gate t he i m pact of missi n g data. T his a p pr oac h ass u mes missi n g o bser vati o ns 
are missi n g at ra n d o m a n d b orr o ws i nf or m ati o n fr o m s u bjects i n t he sa me treat m e nt gr o u p ta ki n g 
i nt o acc o u nt t he missi n g ness of data t hr o u g h t he c orrel ati o n of t h e re p eate d meas ure me nts.  
All c o nti n u o us e n d p oi nts will utilize M M R M after a p pl yi n g t he pri m ar y ce ns ori n g r ule, i.e., t he 
r ule will ce ns or dat a aft er per ma ne nt st u d y dr u g disc o nti n uati o n or aft er res c ue t hera p y. T his 
ce ns ori n g r ule is e q ui v ale nt t o usi n g all t h e data u p t o disc o nti n uati o n or resc ue. 
T he M M R M m o del will i ncl u de fi xe d effects f or b aseli ne val ue, disease se v erit y gr o u p, bi ol o gic-
naï ve vs bi ol o gic-e x p ose d, c o u ntr y, treat me nt, st u d y wee k, t h e tr eat m e nt- b y- wee k i nteracti o n, 
a n d t he b aseli ne- b y- wee k i nteracti o n a n d all o w f or ra n d o m s u bject effects. Treat me nt a n d wee k 
will eac h be fitte d as cate g orical vari a bles. T he m o del will ass u me u nstr uct ure d c o varia nce 
str uct ure. If t h e m o del wit h u nstr uct ure d c o varia nce d oes n ot c o n ver ge, t h e n ot her c o varia nc e 
str uct ures will be c o nsi dere d t o m o del t he wit hi n-s u bject err ors. T he K e n war d- R o gers a p pr oac h 
f or c o m p uti n g de n o mi nat or de grees of free d o m will b e use d t o acc o u nt a p pr o priatel y f or p o oli n g 
of wit hi n-s u bject a n d bet wee n-s u bject varia n ce esti m ates. Efficac y data o n s u bjects w h o 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 1 of 1 3 5 
C o nfi d e nti al  
pre mat urel y disc o nti n ue t he ra n d o mize d treat m e nt or i nitiate a n y treat m e nt a dj ust me nts (e. g., use 
of pr o hi bite d/resc u e me dicati o n/resc ue tr eat m e nt f or A D s y m pt o ms) will b e set t o missi n g at t he 
desi g nate d ti me p oi nts after wit h dra w al or after t h e start of s uc h treat me nt c ha n ges. T h e L S M 
a n d 9 5 % CI f or t h e differe nce b et wee n gr o u ps will be esti m ate d usi n g t he si m ple c o ntrast at eac h 
ti m e p oi nt.
1 6. 6. 3
E x pl or at or y A n al ysis
T he f oll o wi n g e x pl orat or y efficac y e n d p oi nts will b e a nal y ze d:
C ha n ge i n 
 at Wee k 1 4.
Ti me t o o nset of res p o ns e o n t he 
, w here 
res p o nse is defi n e d as i m pr o ve me nt (at least a  
 re d ucti o n fr o m baseli n e) of wee kl y 
a vera g e of d ail y  
 d uri n g t h e 1 4- wee k treat me nt peri o d. T he a n al ysis will be base d o n 
s u bjects w
 
C ha n ge fr o m baseli ne t o Wee k 1 4 i n  
 
 
Safet y a n d t olera bilit y of u p t o 7 d oses of lire nteli ma b S C or place b o S C i n s u bjects wit h 
m o derate-t o-s e vere A D. 
 
P D of lire nteli ma b S C i n s u bjects wit h A D as meas ure d b y c ha n g es fr o m b aseli ne i n 
. 
 
Ot her i n dices of effic ac y of lire nteli ma b S C i n s u bjects wit h A D. C h a n ges i n si g ns a n d 
s y m pt o ms (c o m p are d t o baseli ne) bet w ee n lire nt eli ma b a n d place b o will b e meas ure d b y:  
 C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
 
C ha n ge i n  
 fr o m baseli ne t o Wee k 1 4
 Pr o p orti o n of s u bjects w h o ac hie ve  
 
 Pr o p orti o n of s u bjects w h o ac hie ve  
 
 C ha n ge fr o m baseli ne t o Wee k 1 4 i n 
  
 C ha n ge fr o m baseli ne t o Wee k 1 4 i n  
  
 C ha n ge fr o m baseli ne o v er ti me i n 
 
Ha n dli n g of missi n g P R O data f or l ess t ha n f o ur data e ntries p er w ee k, ot her t h a n d uri n g 
Scree ni n g, will be a d dresse d i n t he S A P. 
1 6. 6. 4  
I nteri m A n al ysis 
A n i nteri m a nal ysis will n ot be c o n d ucte d f or t his st u d y. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 2 of 1 3 5 
C o nfi d e nti al  
1 6. 7
S afet y A n al ysis 
A d verse E ve nts:  All A E will be c o de d usi n g t he Me di cal Dicti o nar y f or R e g ulat or y Acti viti es 
( Me d D R A) a n d will be classifie d b y Me d D R A s yste m or ga n class ( S O C) a n d preferre d t er m. 
Listi n gs will i n cl u de all A E c oll ecte d o n st u d y. T he s u m maries of A E will be base d o n T E A E, 
defi ne d as a n A E re p orte d i n t he cli nical data base wit h a date of o nset ( or w orse ni n g) o n or after 
t he start date of t he first S C i njecti o n of st u d y dr u g.  
1 6. 7. 1
Tre at me nt E mer ge nt A d v erse E ve nts 
S u bject i n ci de nce ( N a n d %) of T E A E will be s u m marize d as f oll o ws: 
 
O ver vie w of T E A E t o i n cl u de 
 N u m ber ( %) of s u bjects w h o re p ort e d at least 1 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 s u bjects w h o re p ort e d at least 1 seri o us T E A E  
 N u m ber ( %) of s u bjects w h o re p ort e d at least 1 T E A E lea di n g t o treat m e nt 
disc o nti n uati o n  
 N u m ber ( %) of s u bjects w h o re p ort e d at least 1 T E A E of s p eci al i nterest ( T E A E SI) 
 
T E A E b y preferre d ter m 
 
T E A E b y S O C a n d preferre d ter m 
 
T E A E b y ma xi m u m se verit y, S O C, a n d preferre d t er m  
 
T E A E b y S O C a n d preferre d ter m a n d rel ati o ns hi p t o st u d y dr u g 
 
T E A E lea di n g t o wit h dra wal b y S O C a n d preferre d ter m  
 
Seri o us T E A E b y S O C a n d preferre d t er m  
 
T E A E SI b y S O C a n d preferre d ter m 
1 6. 7. 2  
A nti- Dr u g A nti b o di es
Sa m ples will be o btai ne d f or testi n g of A D A at ti m es i de ntifie d i n Secti o n  1 2. 3. 6.  
1 6. 7. 3  
Cli ni c al L a b or at or y Assess me nts 
Sa m ples will be o btai ne d f or t he cli nical la b orat or y tests i de ntifie d i n Secti o n  1 2. 3, a n d 
la b orat or y tests t o be s u m marize d i ncl u de c he mistr y, he mat ol o g y, uri nal ysis, a n d lire nteli ma b 
A D A. D escri pti ve statisti cs will be use d t o s u m marize la b orat or y res ults at baseli ne, eac h visit, 
a n d t he c ha n g e fr o m b aseli ne f or eac h visit. I n a d diti o n, s hift ta bles will s u m marize t he 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 3 of 1 3 5 
C o nfi d e nti al  
la b orat or y res ults relati v e t o n or mal refere n ce ra n g es at b aseli ne a n d eac h p ost- baseli ne 
ti m e p oi nt. 
1 6. 7. 4
Vit al Si g ns
Vital si g ns will be s u m marize d at baseli n e, eac h visit, a n d c ha n ge fr o m b aseli ne at eac h visit.  
1 6. 7. 5
E C G
S u bject i n ci de nce of t h e I n vesti gat or’s o verall 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 marize d.
1 6. 7. 6
P h ysic al E x a m
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 x a ms will be i ncl u de d i n t he 
b y-s u bject data listi n g.  
1 6. 7. 7  
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. 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 cl ass a n d preferre d t er m. 
1 6. 7. 8  
S u bject C o nfi de nti alit y 
O nl y t he PI D, a n d de m o gra p hics will be rec or d e d i n t he e C R F c o nsiste nt wit h c o u ntr y 
re g ulati o ns. If t he s u bject’s na me or ot her i de ntifiers (e. g., me dic al rec or d n u m ber or a d dress) 
a p pear o n a n y s o urce d oc u me nt c ollecte d ( e. g., h os pit al dis c har ge s u m m ar y), it m ust be re m o ve d 
fr o m t he d oc u me nt if t he d oc u me nt will b e vie we d b y t he S p o ns or, or a s p o ns or-c o ntracte d st u d y 
ve n d or n ot per mitte d access t o s u bject-i d e 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 dat a bases. T he 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 oriti es, a n d t he I E C/I R B t o i ns pect t h eir me dical rec or ds t o verif y t he 
i nf or mati o n c oll ecte d. S u bjects will be i nf or me d t h at all pers o nal i nf or m ati o n ma de a vaila ble f or 
i ns pecti o n will be ke pt c o nfi de ntial t o t he e xt e nt per mitte d b y all a p plica ble state, l ocal, a n d 
fe deral data pr ot ecti o n/ pri v ac y la ws a n d/ or re g ulati o ns a n d will n ot be ma de p u blicl y a vaila ble. 
If t h e res ults of t he st u d y are p u blis he d, t h e s u bject’s i de ntit y will re mai n c o nfi de ntial.  
At st u d y c hec k-i n t o t h e st u d y site, s u bjects will be a d vise d n ot t o s h are t h eir st u d y i nf or mati o n 
wit h ot h er s u bjects or o n s ocial me dia.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 4 of 1 3 5 
C o nfi d e nti al  
1 7.
D at a C ollecti o n, Rete nti o n, a n d M o nit ori n g 
1 7. 1
D at a C ollecti o n I nstr u m e 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 me ntati o n practi ces. D ata will be 
e ntere d i nt o t he e C R F usi n g s o urce d oc u m e nt data. S o urce d oc u me nts ma y i ncl u de b ut are n ot 
li mite d t o la b orat or y data, rec or 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 nce. 
1 7. 2
D at a M a n a ge me nt Pr oc e d ures 
T he data will be e nt ere d i nt o a vali d ate d data b ase. T he d ata ma n a ge me 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 ualit y ass ura nce pr oce d ures ha ve b ee n c o m plete d. 
All pr oce d ures f or h a n dli n g a n d a nal ysis of data will be c o n d ucte d usi n g g o o d c o m p uti n g 
practi ces m eeti n g F D A g ui deli nes f or ha n dli n g a n d a nal ysis of data f or cli nical st u dies. 
1 7. 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 data bas e, a s yste m of c o m p uterize d data v ali d ati o n 
c hec ks will be i m ple me nte d a n d a p plie d t o t he data base o n a re g ular basis. Q ueries are e nt ere d, 
trac ke d, a n d res ol v e 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 data base will 
be u p date d i n acc or d a nce wit h t h e res ol ve d q ueri es. All c ha n ges t o t he st u d y data base will be 
d oc u me nte d.  
1 7. 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 here will be 2 d ata base l oc ks f or t he d o u ble- bli n d treat me nt peri o d of t h e st u d y:
 
A pr o visi o nal data base l o c k aft er all s u bjects c o m plete t he Da y 9 9 visit t o all o w f or t he 
a nal ysis of safet y a n d efficac y t hr o u g h D a y 9 9.
 
A fi nal data bas e l oc k after all s u bjects c o m plete t h e st u d y t o all o w f or t h e a n al ysis of a n y 
safet y data c ollecte d after Da y 9 9. 
F or eac h dat a base l o c k, a p plica ble E D C data will be l oc ke d i n or der t o pr ot ect write access after 
t he f oll o wi n g prec o n diti o ns are f ulfill e d:
 
All rec or ds are e ntere d i n t h e data base. 
 
All A E are c o de d t o t he s atisfacti o n of t he C hief M e dical Officer or desi g nee. 
 
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 Offic er or desi g nee. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 5 of 1 3 5 
C o nfi d e nti al  
 
All data q ueries h a ve bee n res ol ve d. 
 
All decisi o ns ha ve bee n ma de re g ar 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 xcl usi o ns. 
 
Writte n a ut h orizati o ns t o l oc k t h e data base 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 M e dic al Officer. 
T he ra n d o mi zati o n c o de f or t his st u d y will n ot be re veal e 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 h e pr o visi o nal data base l oc k f or efficac y assess me nt is c o m plete.
After t h e d ata base l o c k, t h e ra n d o mizati o n c o d e will be ma de a vaila ble t o i n di vi d uals at Alla k os 
w h o are i n v ol ve d i n t he d ata a nal ysis. Data a nal ysis will c o m me nce aft er t h e data l oc k. I n 
a d diti o n, t h e P K a n d A D A data m a y be l o c ke d a n d assesse d se p aratel y. 
1 7. 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 base a n d relate d s oft ware files will be m ai ntai ne d. 
Data bases are b ac ke d u p b y t he data base a d mi nistrat or i n c o nj u ncti o n wit h a n y u p dates or 
c ha n ges t o t h e dat a base. At critical j u nct ures of t he pr ot o c ol (e. g., pr o d ucti o n of i nteri m re p orts 
a n d fi nal re p orts), data f or a nal ysis is l oc ke d a n d clea ne d per est a blis he d pr oce d ures.  
1 7. 6
A v ail a bilit y a n d Rete nti o n of I n v esti 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- V § 1 3 ( 1 0), I C H G C P E 6 ( R 2), a n d all ot her 
a p plica ble re g ulat or y re q uire me nts, all esse ntial d oc u me nts at t h e st u d y site, t he S p o ns or’s 
or ga nizati o n or t h e S p o ns or’s desi g nee s h o ul d be retai n e d u ntil at least 2 y ears after t h e l ast 
a p pr o v al of a n a p pli cati o n f or a mar keti n g a ut h ori zati o n i n a n I C H re gi o n, u ntil t here are n o 
pe n di n g or c o nte m plate d a p plicati o ns f or mar k eti n g a ut h orizati o n i n a n I C H re gi o n, a n d u ntil at 
least 2 years h a ve el a pse d si nce t he f or mal dis c o nti n uati o n of cli nical de vel o p me nt of t he teste d 
I M P a n d at least 1 0 years after t h e e n d of t he cli nical st u d y, w hic he ver peri o d is l o n ger. 
F urt her m ore, t h e ess e ntial d oc u me nts s h o ul d be retai ne d f or a l o n g er peri o d if re q uire d b y t h e 
a p plica ble re g ulat or y re q uire me nts or b y a n a gree me nt wit h t he S p o ns or. T he trial master file 
will b e creat e d d uri n g t he i m ple me ntati o n peri o d 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 h e pr oject, a n d c oll ate d at t he e n d of t he st u d y. T he files will c o ntai n 
f ol ders t h at ma y i ncl u de b ut are n ot li mit e 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 oc u m e nts 
 
I E C/I R B d oc u me nts


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 6 of 1 3 5 
C o nfi d e nti al  
 
Dr u g Acc o u nta bilit y d oc u me nts 
 
C orres p o n de nce 
 
Me dical Re p orts 
 
S u bject Data 
 
M o nit ori n g Visit Re p orts 
 
Sa m ple C R F a n d C R F G ui deli nes 
1 7. 7  
M o nit ori n g 
M o nit ori n g visits will b e 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/ or I C H G C P G ui d eli n e E 6. B y si g ni n g t his pr ot oc ol, t he I n vesti g at or 
gra nts per missi o n t o t h e S p o ns or ( or desi g nee) a n d a p pr o priate re g ulat or y a ut h 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, I E C/I R B re vie w a n d re g ulat or y i ns pecti o ns of all a p pr o priat e 
st u d y d oc u me ntati o n, pr o vi di n g direct access t o s o urce dat a a n d d oc u m e nts. M o nit ori n g of all 
a p pr o priate st u d y d oc u m e nt ati o n ma y o cc ur off-site, wit h re m ote access t o st u d y d oc u me nts if 
all o we d b y l ocal re g ulati o n, as per mitte d b y i n di vi d ual st u d y site re q uire m e nts.  
1 8.
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 his pr ot o c ol, t he Declarati o n of 
Helsi n ki ( 1 9 9 6 versi o n), I R B/I E C ( 2 1 C F R 5 6 a n d/ or 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/ or I C H E 6), Directi v e 2 0 0 1/ 2 0/ E C ( A pril 4, 2 0 0 1) as well as 
ot her a p pli ca ble l o cal re g ulati o ns i ncl u di n g Ger ma n y’s Me dici nal Pr o d ucts Act ( A M G), 
Ger m a n y’s G C P Or di n a nce ( G C P- V), etc. T h e S p o ns or, t he I n vesti g at ors, a n d all s u bc o ntracte d 
or ga nizati o ns i n v ol ve d i n t he st u d y c o n d uct m ust als o c o m pl y wit h all a p plica ble pri vac y 
re g ulati o ns (e. g., HI P A A, G D P R). T he st u d y ca n be i nitiate d o nl y after o bt ai ni n g c o m p ete nt 
a ut h orit y a p pr o val a n d I R B a n d/ or I E C fa v ora bl e o pi ni o n. If t he c o m p ete nt a ut h orit y wit h dra ws 
t he C T A a p pr o val or if t h e I R B wit h dra ws t he fa v ora ble o pi ni o n o n t he C T A, t he c o n d uct of t he 
st u d y will be ter mi n ate d i m m e diatel y. 
1 8. 1  
Pr ot oc ol A me n d m e nts  
A n a me n d me nt m ust be a gree d t o i n writi n g b y Alla k os I nc. a n d s u b mitte d t o t he healt h a ut h orit y 
as a n I n vesti gati o nal N e w Dr u g (I N D) a me n d me nt. A n a me n d me nt w hic h is c o nsi dere d 
s u bsta ntial acc or di n g t o t he E C C T- 1 g ui deli nes, m ust be s u b mitt e d f or re vie w t o t he c o m p ete nt 
a ut h orit y a n d t he res p o nsi ble I E C/I R B a n d ca n n ot be i m ple me nte d wit h o ut pri or writt e n 
c o m pete nt a ut h orit y a p pr o val a n d t he I E C/I R B fa v ora ble o pi ni o n. Writte n a p pr o val of a pr ot o c ol 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 7 of 1 3 5 
C o nfi d e nti al  
a me n d me nt is n ot re q uire d pri or t o i m ple me nt ati o n of c ha n ges t o t he pr ot oc ol t hat eli mi nate 
i m m e diate h azar d t o t h e s u bject; h o we ver, a p pr o v al m ust be o btai ne d as s o o n as p ossi ble 
t hereafter. E ac h pr ot oc ol a me n d me nt m ust als o be si g ne d b y t he I n vesti gat or. 
1 8. 2
I n de pe n de nt Et hics C o m mittees/I nstit uti o n al Re vie w B o ar ds
T he pr ot o c 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 he I E C/I R B of eac h partici 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 
site. All S A E, re gar dless of ca usalit y, will be re p orte d t o t he I E C/I R B i n acc or da nce wit h t he 
sta n dar d o perati n g pr oce d ures a n d p olicies of t h e I E C/I R B, a n d t h e I n v esti g at or will k ee p t h e 
I E C/I R B i nf or me d as t o t h e pr o gress of t h e st u d y. T he I n vesti g at or or a desi g nee will o btai n 
ass ura nce of I E C/I R B c o m plia nce wit h re g ulati o ns.  
A n y d oc u m e nts t hat t he I E C/I R B m a y nee d t o f ulfill its res p o nsi biliti es (s uc h as pr ot o c ol, 
pr ot oc ol a me n d me nts, I n vesti gat or’s Br oc h ure, I C F, i nf or mati o n c o n cer ni n g s u bject recr uit me nt, 
pa y me nt or c o m pe ns ati o n pr oce d ures, or ot her perti ne nt i nf or mati o n) will be s u b mitte d t o t he 
I E C/I R B. T he I E C/I R B’s writte n u nc o n diti o nal a p pr o val of t he st u d y pr ot o c 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 g at or bef ore t h e st u d y is i niti ate d. T he I E C/I R B’s a p pr o v al of 
t he i n vesti gati o nal site m ust be a vaila bl e t o Alla k os pri or t o s hi p me nt of st u d y s u p plies t o t h e 
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.  
T he I E C/I R B m ust be i nf or me d of re visi o ns t o ot h er d oc u me nts ori gi nall y s u b mitte d f or re vie w; 
seri o us a n d/ or u ne x p ecte d a d verse e x perie nces o cc urri n g d uri n g t h e st u d y i n acc or d a nce wit h t he 
sta n dar d o perati n g pr oce d ures a n d p olicies of t h e I E C/I R B; ne w i nf or m ati o n t hat ma y a d vers el y 
affect t he safet y of s u bjects or t he c o n d uct of t h e st u d y; a n a n n ual u p date a n d/ or re q uest f or 
rea p pr o v al; a n d w he n t h e st u d y has bee n c o m plete d.  
1 8. 3  
I nf or me d C o nse nt F or m 
Pri or t o st u d y e nr oll m e nt, all s u bjects m ust c o nse nt t o partici pate i n writi n g. T he pr ocess of 
o btai ni n g t h e i nf or me d c o nse nt will c o m pl y wit h all fe d eral re g ulati o ns, I C H re q uire me nts, a n d 
l ocal la ws.  
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 h e y 
w o ul d li k e t h eir pri mar y care p h ysi cia n n otifie d of t heir st u d y partici pati o n. If yes, t h e pri mar y 
care p h ysi cia n s h o ul d 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 oes n ot wis h t o discl ose s uc h i nf or mati o n.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 8 of 1 3 5 
C o nfi d e nti al  
T he I n vesti gat or or d esi 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 ntial s u bject. T he 
re vie w will i ncl u de t h e 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 parti ci 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 date t he I C F after 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, i.e., bef ore a n y st u d y-s p ecific pr oce d ures are c o n d uct e d. 
T he s u bject will rec ei ve a c o p y of t he si g ne d a n d d ate d f or m, a n d t h e ori gi nal will be retai ne d i n 
t he site’s st u d y files. T he I n v esti gat or or d esi g nee m ust e m p hasize t o t he s u bject t hat st u d y 
partici pati o n is e ntirel y v ol u ntar y a n d t h at c o nse nt re g ar di n g st u d y partici pati o n ma y be 
wit h dra w n at a n y ti me wit h o ut pe nalt y or l oss of be nefits t o w hic h t he s u bject is ot her wise 
e ntitle d.  
1 8. 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 bli cati o n of ma n uscri pts c o ntai ni n g t he st u d y res ults will be 
i n acc or d a nce wit h a pr o cess deter mi ne d b y m ut u al writt e n a gree me nt a m o n g t he st u d y S p o ns or 
a n d res p ecti v e sit e(s). T h e p u blicati o n or pres e ntati o n of a n y st u d y res ults will c o m pl y wit h all 
a p plica ble pri v ac 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 of 1 9 9 6 a n d t he E U G e neral D ata Pr otecti o n Re g ulati o n ( G D P R).  
1 8. 5
Cli nic al St u d y Re gistr ati o n
T his cli nical st u d y will be re gistere d o n t he Cli nical Trial Re gistr y We bsites, 
w w w. Cli nical Trials. g o v a n d w w w.cli nic altrialsre gister.e u.
1 8. 6
P a y me nt t o S u bjects 
All s u bjects m a y be 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 da nce wit h t he pa y me nt 
a m o u nts per st u d y da 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 I E C/I R B. I n 
acc or d a nce wit h Secti o n 4. 8. 3 I C H E 6 ( R 2), fi na n cial c o m pe nsati o n fr o m t he s p o ns or t o 
partici pati n g s u bjects s hall be li mite d t o t he rei m b urse me nt of a n y tra vel e x pe nses i nc urre d 
( Ger ma n y o nl y). 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 last st u d y visit, t he 
s u bject will be c o m pe nsate d f or eac h c o m plete d st u d y visit o n a pr o rata basis, as state d i n t he 
s u bject’s I C F. Be gi n ni n g wit h d osi n g Da y 1, s u bjects will be c o m pe nsate d f or eac h c o m plete d 
wee k of d ail y q uesti o n naires as l o n g as at le ast 4 q uesti o n naires per wee k are c o m plete d. 
S u bjects m a y be rei m b urse d f or e x p e nses ass o ciat e 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 h at is state d i n t he I C F is per mitte d.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 0 9 of 1 3 5 
C o nfi d e nti al  
1 8. 7
I n vesti g at or R es p o nsi bilities 
B y si g ni n g t he I n vesti gat or Pr ot o c ol A gre e me nt pa ge, t h e I n v esti 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 o c ol a n d o nl y ma ke c ha n g es after n otif yi n g 
t he S p o ns or ( or d esi g nee), e xce 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 h e st u d y. 
3) 
E ns ure t h at t h e re 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 E C/I R B re vie w 
a n d a p pr o val meet c o u ntr y re q uire me nts. 
4) 
Re p ort t o t he S p o ns or or desi g nee a n y A E t hat occ ur i n t he c o urse of t he st u d y, i n 
acc or d a nce wit h 2 1 C F R Part 3 1 2. 6 4 a n d/ or I C H G ui deli ne E 2 A.  
5) 
E ns ure t h at all ass ociat es, c ollea g ues, a n d e m pl o yees 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 he a b o ve c o m mit m e 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/ or 
I C H G ui d eli ne E 6 a n d t o ma ke 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 d esi g nee).  
7) 
E ns ure t h at a n I E C/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/ or I C H 
G ui deli ne E 6 as a p plica ble will be res p o nsi ble f or i niti al a n d c o nti n ui n g re vie w a n d 
a p pr o v al of t he cli nical st u d y.  
8) 
Pr o m ptl y re p ort t o t he I E C/I R B a n d t h e S p o ns or ( or desi g nee) all c ha n g es i n t he researc h 
acti vit y a n d all u na nti ci pate d pr o ble ms i n v ol vi n g ris ks t o s u bjects or ot h ers (t o i n cl u de 
a me n d me nts a n d I N D s afet y re p orts).  
9) 
See k I E C/I R B a p pr o val bef ore a n y c ha n ges are m a de i n t he res ear c h st u d y, e xce pt w h e n 
necessar y t o eli mi nate h azar ds t o t h e s u bjects. 
1 0) 
C o m pl y wit h all ot her re q uire me nts re gar di n g t he o bli g ati o ns of cli nical I n vesti gat ors a n d 
all ot her perti ne nt re q uire me nts liste d i n 2 1 C F R Part 3 1 2 a n d/ or I C H G ui d eli ne E 6.  


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 0 of 1 3 5 
C o nfi d e nti al  
1 9.
Refere nces 
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.
Castr o
M, C orre n J, Pa v or d I, Mas per o J, We n zel S, Ra be K, et al. D u pil u ma b efficac y a n d 
safet y i n m o derat e-t o-se v ere u nc o ntr olle d ast h ma. N E n gl J
Me d, 2 0 1 8; 3 7 8: 2 4 8 6 – 9 6.
Cli nical Trials Facilitati o n a n d C o or di nati o n Gr o u p ( C T F G). R ec o m m e n dati o ns relate d t o 
c o ntrace pti o n a n d pre g n a nc y testi n g i n cli nical trials, versi o n 1. 1. 2 1 Se p 2 0 2 0, accesse d 
2 8 J u n 2 0 2 2, htt ps://le ge mi d del ver ket. n o/ D oc u me nts/ G o d kje n ni n g/ Kli nis k % 2 0 ut pr % 
C 3 % B 8 vi n g/ 2 0 1 4 _ 0 9 _ H M A _ C T F G _ C o ntrace pti o n _ g ui da nce % 2 0 Versi o n % 2 0 1. 1. p df.
C orre n J, Par nes J, Wa n g L, M o M, R oseti S, Griffit hs J, va n der Mer we R. Teze p el u ma b i n 
a d ults wit h u nc o ntr olle d ast h ma. N E n gl J Me d, 2 0 1 7; 3 7 7: 9 3 6 – 4 6.
Eic he nfiel d L, T o m W, C ha mli n S, Fel d ma n S, Ha nifi n J, Si m ps o n E, et al. G ui deli nes of care 
f or t h e m a na g e me nt of at o pic der m atitis: Part 1. Dia g n osis a n d assess m e nt of at o pic 
der matitis. J A m Aca d D er m at ol, 2 0 1 4; 7 0: 3 3 8 – 5 1.
F o o d a n d Dr u g A d mi nistrati o n. Birt h C o ntr ol C h art fr o m F D A. g o v/c o ns u mers/free- p u bli cati o ns-
w o me n/ birt h-c o ntr ol. F D A. g o v/c o ns u mers/free- p u blicati o ns- w o me n/ birt h-c o ntr ol, 
2 1 J u n 2 0 2 1, retrie ve d 2 7 Fe b 2 0 2 2, fr o m htt ps:// w w w.f da. g o v/c o ns u mers/free-
p u blicati o ns- w o m e n/ birt h-c o ntr ol.
F o o d a n d Dr u g A d mi nistrati o n. E 9 ( R 1) Statisti cal Pri nci ples f or cli nical trials: a d de n d u m: 
esti ma n ds a n d se nsiti vit y a nal ysis i n cli nical trials. G ui da nce f or i n d ustr y, I C H, Ma y 
2 0 2 1.
F u xe nc h Z, Bl oc k J, B o g u nie wicz M, B o yle J, F o nacier L, Gelfa n d J, et al. At o pic der matitis i n 
A merica st u d y: A cr oss-s ecti o nal st u d y e xa mi ni n g t he pre vale n ce a n d disease b ur de n of 
at o pic der matitis i n t he U S a d ult p o p ulati o n. J I n v est Der mat ol, 2 0 1 9; 1 3 9: 5 8 3 – 9 0. 
Sa m ps o n H, M u n oz- F url o n g A, Ca m p bell R, A d ki ns o n Jr N, B oc k S, Bra n u m A, et al. S ec 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 yla xis: s u m mar y re p ort-- Sec o n d 
Nati o nal I nstit ute of Aller g y a n d I nfecti o us Disease/ F o o d Aller g y a n d A na p h yla xis 
Net w or k s y m p osi u m. J Aller g y Cli n I m m u n ol 2 0 0 6; 1 1 7( 2): 3 9 1 – 7 
Sil ver ber g J, Si m ps o n E, T h ysse n J, G o o der h a m M, C ha n G, Fee ne y C, Bis was P, et al. Efficac y 
a n d safet y of a br ociti ni b i n patie nts wit h m o derate-t o-se vere at o pic d er matitis: Res ults 
fr o m t he P hase 3 J A D E M O N O- 2 St u d y. A bstract 1 4 8 p oster, R A D 2 0 2 0. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 1 of 1 3 5 
C o nfi d e nti al  
Si m ps o n E, Fl o hr C, Eic he nfiel d L, Bie ber T, S ofe n H, Taïe b A, et al. Efficac y a n d safet y of 
le bri kiz u ma b (a n a nti-I L- 1 3 m o n ocl o nal a nti b o d y) i n a d ults wit h m o derate-t o-se vere 
at o pic der matitis i na de q u atel y c o ntr olle d b y t o pical c orti c oster oi ds: A ra n d o mi ze d, 
place b o-c o ntr olle d p hase II trial ( T R E B L E). J A m Aca d D er m at ol, 2 0 1 8; 7 8: 8 6 3 – 7 1. 
Si m ps o n E, Paller A, Si e gfrie d E, B o g u nie wicz M, S her L, G o o der h a m M, et al. Efficac y a n d 
safet y of d u pil u ma b i n a d olesce nts wit h u nc o ntr olle d m o derate t o s e vere at o pic 
der matitis: A p hase 3 ra n d o mize d cli nical trial. J A M A Der mat ol, 2 0 2 0; 1 5 6: 4 4 – 5 6. 
Si m ps o n E, Par nes J, S h e D, Cr o uc h S, Rees W, M o M, va n der Mer we R. Teze pel u ma b, a n 
a nti-t h y mic str o mal l y m p h o p oieti n m o n ocl o nal a nti b o d y, i n t he treat m e nt of m o derate t o 
se vere at o pic der m atitis: A ra n d o mize d p h ase 2a cli nical trial. J A m Aca d D er mat ol, 
2 0 1 9; 8 0: 1 0 1 3 – 2 1.
W olle n ber g A, H o well M, G utt ma n- Yass k y E, Sil ver ber g J, K ell C, Ra na de K, et al. Treat me nt 
of at o pic der m atitis wit h tral o ki n u ma b, a n a nti-I L- 1 3 m A b. J Aller g y Cli n I m m u n ol, 
2 0 1 9: 1 4 3: 1 3 5 – 4 1.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 2 of 1 3 5 
C o nfi d e nti al  
2 0.
A p pe n di ces 
2 0. 1 
A p pe n di x 1: 
At o pic Der matitis: A merica n Aca de m y of D er mat ol o g y C o nse ns us Criteria 
2 0. 2 
A p pe n di x 2: 
Vali date d I n vesti gat or Gl o bal Assess me nt
2 0. 3 
A p pe n di x 3: 
Ecze m a Area a n d Se v erit y I n d e x  
2 0. 4 
A p pe n di x 4: 
2 0. 5 
A p pe n di x 5: 
2 0. 6 
A p pe n di x 6: 
2 0. 7 
A p pe n di x 7: 
At o pic C o n diti o ns Q uesti o n naire 
2 0. 8 
A p pe n di x 8: 
C o m m o n Ter mi n ol o g y Criteria f or A d vers e E ve nts v. 5. 0 
2 0. 9 
A p pe n di x 9: 
Sa m ps o n’s Criteria of A n a p h yla xis 
2 0. 1 0 
A p pe n di x 1 0: He patitis B a n d He p atitis C Ser ol o gic Testi n g Details
2 0. 1 1 
A p pe n di x 1 1: O pe n La b el E xt e nsi o n Peri o d ( O pti o nal) 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 3 of 1 3 5 
C o nfi d e nti al  
2 0. 1
A p p e n di x 1:
At o pic Der m atitis – A meric a n Ac a de m y of Der m at ol o g y 
 
C o ns e ns us Criteri a
A da pt e d fr o m G ui d eli nes of C are f or t h e M a na ge me nt of At o pic D er m atitis: Part 1. Dia g n osis 
a n d Ass ess me nt Of At o pic Der matitis, , J o ur nal of t h e A merica n Aca d e m y of Der mat ol o g y 
( Eic he nfiel d, 2 0 1 4).


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 4 of 1 3 5 
C o nfi d e nti al  
2 0. 2
A p p e n di x 2:
V ali d ate d I n v esti g at or Gl o b al Assess me nt 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 5 of 1 3 5 
C o nfi d e nti al  
2 0. 3
A p p e n di x 3:
Ecze m a Are a a n d Se verit y I n de x 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 6 of 1 3 5 
C o nfi d e nti al  
2 0. 3
A p p e n di x 3:
Ecze m a Are a a n d Se verit y I n de x c o nt.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 7 of 1 3 5 
C o nfi d e nti al  
2 0. 3
A p p e n di x 3:
Ecze m a Are a a n d Se verit y I n de x c o nt.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 8 of 1 3 5 
C o nfi d e nti al  
2 0. 3
A p p e n di x 3:
Ecze m a Are a a n d Se verit y I n de x c o nt.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 1 9 of 1 3 5 
C o nfi d e nti al  
2 0. 3
A p p e n di x 3:
Ecze m a Are a a n d Se verit y I n de x c o nt.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 2 0 of 1 3 5 
C o nfi d e nti al  
2 0. 3
A p p e n di x 3:
Ecze m a Are a a n d Se verit y I n de x c o nt.


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 2 1 of 1 3 5 
C o nfi d e nti al  
2 0. 3
A p p e n di x 3:
Ecze m a Are a a n d Se verit y I n de x c o nt.








Pr ot o c ol A K 0 0 2- 0 1 8
A me n d m e nt 6
Date: 0 8 Se pte m b er 2 0 2 3
Alla k os I nc.
Pa ge 1 2 5 of 1 3 5
C o nfi d e nti al
2 0. 7
A p p e n di x 7:
At o pic C o n diti o ns Q u esti o n n aire




Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 2 7 of 1 3 5 
C o nfi d e nti al  
2 0. 9
A p p e n di x 9: 
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 yla xis (cli nical defi niti o n) is t he ac ute o nset of 
ill n ess ( mi n utes t o se veral h o urs) w hic h i n v ol ves S KI N, M U C O S A L TI S S U E , or B O T H  (e. g., 
ge neralize d hi ves, pr urit us or fl us hi n g, s w olle n li ps-t o n g ue u v ula) wit h 1 O R m ore of t he 
f oll o wi n g ( Sa m ps o n, 2 0 0 6):
R E S PI R A T O R Y : Air wa y c o m pr o mise (e. g., d ys p nea, w heeze, or br o n c h os pas m, stri d or, 
re d u ce d P E F, h y p o xe 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 ncti o n (e. g., h y p ot o nia, s y nc o pe) 
O R
2 or M O R E of t h e 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 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 ncti o n (e. g., h y p ot o nia, s y nc o pe) 
 
G A S T R OI N T E S TI N A L : Persiste nt gastr oi ntesti 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 o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 2 8 of 1 3 5 
C o nfi d e nti al  
2 0. 1 0
A p p e n di x 1 0:
He p atitis B a n d He p atitis C Ser ol o gic T esti n g Det ails 
He p atitis B T esti n g Det ails 
H Bs A g p ositi ve s u bjects are e x cl u de d. H o we ver, i n cas e of p ast i nfecti o ns/ vacci n ati o ns i n or der 
t o q ualif y, t he s u bject’s t esti n g stat us nee ds t o ali g n wit h t he i nf or mati o n i n Ta ble 6. 
T a bl e 6  
He p atitis B Testi n g
P ast I nfecti o n ( Res ol v e d) 
Or 
V a cci n ate d 
H Bs A g 
Ne g ati v e 
H Bs A g 
Ne gati v e 
A nti- H Bc
P ositi v e
A nti- H Bc
N e g ati v e
A nti- H Bs
P ositi v e
A nti- H Bs
P ositi v e
He p atitis C Testi n g Det ails 
A nti- H C V p ositi v e a n d H C V- R N A p ositi ve are e xcl u de d. I n or der t o q ualif y f or e nr oll m e nt, t he 
s u bject’s testi n g stat us nee ds t o ali g n wit h t he i nf or mati o n i n Ta ble 7. 
T a bl e 7  
He p atitis C Testi n g 
N o n- R e acti ve 
Or 
P ast I nfecti o n ( Res ol v e d)
A nti- H C V 
N e gati v e 
A nti- H C V 
P ositi v e 
H C V R N A 
N e g ati v e 
 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 2 9 of 1 3 5 
C o nfi d e nti al  
2 0. 1 1
A p p e n di x 1 1: 
O pe n L a bel E xte nsi o n Peri o d ( O pti o n al)
2 0. 1 1. 1  S u m m ar y of t he O pe n- L a bel E xte n de d D osi n g Peri o d 
S u bjects w h o c o m plete t he d o u ble- bli n d, place b o-c o ntr olle d treat me nt peri o d (i ncl u di n g t he 
Da y 9 9 st u d y visit) a n d meet t h e o pe n-la b el e xte n de d d osi n g eli gi bilit y criteria will be gi v e n t h e 
o pti o n t o recei ve 7 d oses of 3 0 0 m g lire nteli ma b S C t hr o u g h t he o pe n-la bel e xte n de d ( O L E) 
d osi n g peri o d. 
O n Da y 9 9 ( ± 5 da ys) of t he d o u ble- bli n d peri o d, eli gi ble s u bjects partici pati n g i n t he O L E peri o d 
will b e gi n f oll o wi n g t he O L E S c he d ule of E v e nts ( Ta ble 8) a n d will n o l o n ger f oll o w t h e d o u ble-
bli n d peri o d Sc he d ule of E ve nts ( Ta ble 1). If O L E Da y 1 is c o m plete d o n t he sa me da y as 
Da y 9 9, alrea d y c o m plet e d assess me nts (f or Da y 9 9) d o n ot nee d t o be re p eate d (f or O L E 
Da y 1), as l o n g as t h e y are perf or me d wit hi n ti m e fra mes n ote d i n t he  T a ble 8 n otes. 
T he O L E d osi n g peri o d is s u m marize d as f oll o ws: 
 
T he I n vesti gat or will e v al u ate w het her t h e s u bject is eli gi ble f or O L E. If eli gi ble, t he 
s u bject will be gi ve n t he o pti o n t o partici pate i n t h e O L E peri o d a n d recei v e 7 d oses of 
o pe n-la bel 3 0 0 m g lire nt eli ma b S C a d mi nistere d e ver y 2 w ee ks starti n g o n Da y 9 9 of t h e 
d o u ble- bli n d peri o d, w hi c h will be c o nsi dere d Da y 1 of t h e O L E peri o d. O L E d osi n g ma y 
be dela ye d f or u p t o 7 da ys after c o m pleti o n of t h e Da y 9 9 visit. 
 
O n Da y 9 9, after c o m pleti n g all Da y 9 9 assess me nts, eli gi ble s u bjects w h o c h o ose t o 
partici pate i n t he O L E p eri o d will be gi n f oll o wi n g t he O L E Sc he d ule of E v e nts ( Ta ble 8). 
 
Da y 1 of t h e O L E ca n o c c ur u p t o 7 da ys f oll o wi n g Da y 9 9 of t h e d o u ble- bli n d peri o d. I n 
case D a y 1 of t h e O L E is n ot t he sa me as Da y 9 9 of t h e d o u ble- bli n d peri o d, a p pli ca ble 
s u bjects ( w o m e n of c hil d beari n g p ote ntial) will ha ve a uri ne di pstic k pre g n a nc y test. 
After O L E Da y 1, s u bse q ue nt d oses will be gi ve n o n O L E Da ys 1 5, 2 9, 4 3, 5 7, 7 1, a n d 8 5 
( ± 5 da ys).  
All differe ntial bl o o d c o u nts will be bli n de d t o t he S p o ns or a n d t h e sit e u ntil aft er O L E Da y 
1 d osi n g. 
S u bjects will re mai n at t he site f or at least 1 h o ur of o bser v ati o n after e ac h d ose. I n t he 
e ve nt of a n I R R, t he s u bj ect ma y re q uire pr ol o n ge d o bser vati o n ( > 1 h o ur or u ntil t he 
s y m pt o ms res ol v e), as per I n vesti gat or discreti o n.  
S u bjects will be f oll o we d f or a p pr o xi matel y 1 2 w ee ks after t h e last d ose. F oll o w- u p visits 
will o cc ur o n O L E D a ys 9 9, 1 4 1, a n d 1 6 9 ( 1 4, 5 6, a n d 8 4 [ ± 5] da ys) f oll o wi n g t he last d ose 
of o pe n-la b el st u d y dr u g. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 3 0 of 1 3 5 
C o nfi d e nti al  
 
If 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 b y t he O L E D a y 1 6 9 
visit (last f oll o w- u p visit), s u bjects will ret ur n a p pr o xi m atel y e ver y 2 8 da ys f or e xte n d e d 
f oll o w- u p u ntil c o u nts ha ve rec o v ere d.
2 0. 1 1. 2  O L E O bjecti v e 
T he o bjecti ve of t h e O L E peri o d is t o e val uate l o n g-ter m safet y a n d t olera bilit y of u p t o 7 d oses 
of o pe n-la b el A K 0 0 2 i n s u bjects wit h A D. T he Me dical M o nit or will re vie w data fr o m t he O L E 
peri o d relati n g t o safet y a n d t olera bilit y t hr o u g h o ut t he c o urse of O L E d osi n g. 
2 0. 1 1. 3  O L E Eli gi bilit y Criteri a 
F oll o wi n g c o m pleti o n of t h e ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d treat m e nt peri o d 
(i ncl u di n g t he Da y 9 9 visit), eli gi ble s u bjects will ha ve t he o pti o n t o recei v e 7 d oses of 
o pe n-la bel 3 0 0 m g lire nt eli ma b S C t hr o u g h partici pati o n i n t h e O L E peri o d. 
S u bjects w h o are n ot eli gi ble or w h o c h o ose n ot t o partici pate i n t he O L E p eri o d, will re m ai n i n 
t he d o u ble- bli n d st u d y a n d c o nti n ue t o f oll o w t he d o u ble- bli n d peri o d Sc he d ule of E ve nts 
( Ta ble 1). 
2 0. 1 1. 4  O L E I ncl usi o n Criteri a 
S u bjects are eli gi ble t o p artici p ate i n t he O L E p eri o d if all t he f oll o wi n g criteria are met: 
1) 
S u bject c o m plete d t he ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d treat m e nt peri o d, 
defi ne d as h a vi n g recei ve d all 7 S C i njecti o ns of st u d y dr u g (lire nteli ma b or place b o), a n d 
c o m plete d t he D a y 9 9 visit pr oce d ures. 
2) 
S u bject is willi n g a n d a ble t o c o m pl y wit h t he O L E peri o d Sc he d ule of E ve nts ( Ta ble 8),
i ncl u di n g recei vi n g t he first o pe n-la bel 3 0 0 m g lire nteli m a b S C at t he Da y 9 9 visit w hic h is 
1 4 da ys f oll o wi n g t he last d ose of st u d y dr u g i n t h e d o u ble- bli n d peri o d or u p t o 7 da ys 
after t he c o m pleti o n of t h e Da y 9 9 visit. 
3) 
S u bject de m o nstrates c o nti n ue d eli gi bilit y per a p plica ble i n cl usi o n criteria ( Secti o n  8. 4) a n d 
e xcl usi o n crit eria ( Secti o n  8. 5) of t he pr ot o c ol. “ Scree ni n g ” i n Secti o n 1 3. 1. refers o nl y t o 
t he scree ni n g peri o d c o m plete d pri or t o e nr oll me nt i n t he d o u ble- bli n d treat m e nt peri o d of 
t he st u d y a n d is n ot a p plica ble t o t he O L E p eri o d. 
2 0. 1 1. 5  O L E E xcl usi o n Criteri a 
S u bjects are n ot per mitte d t o partici pate i n t he O L E p eri o d if a n y of t h e f oll o wi n g criteria are
met:


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3  
Alla k os I nc. 
Pa ge 1 3 1 of 1 3 5 
C o nfi d e nti al  
1) 
Pre vi o us a d mi nistrati o n of t h e st u d y dr u g (lire nteli ma b or place b o) w as p o orl y t olerate d b y 
t he s u bject, i n t he o pi ni o n of t he I n vesti gat or. 
2) 
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 m a kes t he 
s u bject u ns uita ble f or partici pati o n i n t h e O L E peri o d. 
Acce pt a ble d oc u me ntati o n re q uire d t o c o nfir m i ncl usi o n a n d e xcl usi o n crit eria will be f urt h er 
e x plai n e d i n t he St u d y Refere nc e Ma n ual.
2 0. 1 1. 6  O L E Tre at me nt 
F or m ulati o n, st ora g e, pre parati o n, a n d a d mi nistrati o n of t h e o pe n-la b el lire nteli ma b S C f or O L E 
will b e c o nsiste nt wit h Secti o n  1 0. of t he pr ot o c ol a n d t he A K 0 0 2- 0 1 8 P har mac y Ma n u al. 
T he first O L E st u d y dr u g a d mi nistrati o n of o pe n-l a bel 3 0 0 m g lire nteli ma b S C will be d o ne o n 
Da y 9 9 of t h e d o u ble- bli n d peri o d. T his will be c o nsi dere d Da y 1 of t he O L E peri o d. O L E 
d osi n g ma y be dela ye d f or u p t o 7 da ys after t he c o m pleti o n of t he Da y 9 9 visit. T he s u bse q ue nt 
i njecti o ns will occ ur o n Da ys 1 5, 2 9, 4 3, 5 7, 7 1, a n d 8 5 ( ± 5 da ys). 
T he s u bject will be o bser ve d f or at least 1 h o ur ( or l o n ger as per I n vesti gat or discreti o n) after t h e 
e n d of t h e i njecti o n. I n t h e e ve nt of a n I R R, t h e s u bject ma y re q uir e pr ol o n ge d o bser vati o n 
( > 1 h o ur or u ntil s y m pt o ms res ol ve), as p er I n v esti gat or discreti o n. S u bjects will als o be 
i nstr ucte d t o i m m e diatel y c o ntact t he st u d y d oct or if a n y reacti o ns occ ur aft er dis c har g e. 
2 0. 1 1. 7  O L E Pr oce d ures a n d G ui deli nes 
T he O L E peri o d will be c o n d ucte d i n acc or d a nce wit h  Ta ble 8 ( Sc he d ule of Assess me nts: 
O pe n- La bel E xte nsi o n Peri o d) a n d t h e pr ot oc ol. T his i n cl u des pr o hi bite d me dicati o ns, st u d y 
dr u g pre p arati o n a n d a d mi nistrati o n, st u d y assess me nt a n d pr oce d ure g ui d eli n es, A E re p orti n g, 
wit h dra wal crit eria a n d st o p pi n g r ul es, data c oll ecti o n a n d ma na ge me nt, a n d et hical a n d 
re g ulat or y re q uire me nts. 
T he I n vesti gat or will e v al u ate w het her t h e s u bject is eli gi ble f or t h e O L E p eri o d. O n Da y 9 9, 
eli gi ble s u bjects t h at c h o ose t o parti ci pate i n t he O L E peri o d will be gi n f oll o wi n g t he O L E
Sc he d ule of E ve nts ( T a bl e 8)  a n d will recei v e t h e first o pe n-la bel d ose of lire nteli ma b. 






Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3 
Alla k os I n c.
Pa g e 1 3 4 of 1 3 5
C o nfi d e nti al
T a ble 8 N otes c o nt. 
3) 
E O S visits s h o ul d be c o n d ucte d 1 4 ( ± 5) d a ys after t he last d ose of O L E or pri or t o t his, if necessar y, t o e ns ure c o m plia n ce wit h t h e visit. If a s u bject disc o nti n u es t he st u d y 
> 1 4 d a ys after last d ose of st u d y dr u g, t h e E O S visit s h o ul d b e c o n d u cte d as s o o n as p ossi ble. 
4) 
B o d y wei g ht (i n k g) will b e meas ure d o n all d osi n g a n d f oll o w- u p da ys ( 1 4, 5 6, a n d 8 4 d a ys after t he last d ose of st u d y dr u g if E T). 
5) 
Vital si g ns will b e meas ure d o n all d osi n g a n d f oll o w- u p d a ys ( 1 4, 5 6, a n d 8 4 da ys after t he last d ose of st u d y dr u g if E T). O n all d osi n g d a ys: wit hi n 3 0 mi n utes pre d ose, 
1 5 ( ± 5) mi n utes after a d mi nistrati o n of st u d y dr u g S C i njecti o n, a n d j ust pri or t o disc h ar g e. A d diti o n al vital si g n meas ure me nts ma y be c ollecte d at t h e I n v esti g at or’s 
discreti o n if a n I R R o cc urs. Vital si g ns i n cl 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 p erat ure, a n d res pirat or y rate will b e meas ure d after t h e s u bject h as 
a n d b ef ore a n y bl o o d dra ws h a ve b ee n o btai n e d ( u nless c ollecte d f or a n I R R). 
6) 
A s y m pt o m- directe d p h ysical e xa m (i n cl u di n g assess me nt of p ossi ble i njecti o n site reacti o ns) will b e perf or me d b y t h e I n v esti gat or or d esi g nee, as n ee d e d, if a n y s y m pt o ms 
are re p orte d. 
7) 
T h e vI G A, E A SI, 
 will be ca pt ure d t hr o u g h o ut t h e O L E peri o d. S u bjects e nteri n g i nt o t h e O L E peri o d of t h e st u d y s h o ul d c o nti n u e c o m pleti n g 
t he P R O d ail y. T h e P R O s h o ul d b e c o m plete d ar o u n d t h e sa me ti me eac h d a y.  
8) 
S u bjects will b e pr o m pte d t o a ns wer a d diti o n al q u esti o ns a b o ut s y m pt o ms relate d t o ast h ma, aller gic r hi nitis, a n d aller gic c o nj u n cti vitis ( At o pic C o n diti o ns Q u esti o n n aire). 
9) 
Bl o o d sa m ples f or t otal ser u m I g E will b e c ollecte d d uri n g pre d ose o n O L E Da ys 1, 5 7, a n d 8 5 a n d o n f oll o w- u p Da ys 9 9, 1 4 1, a n d 1 6 9 or 1 4, 5 6, a n d 8 4 ( ± 5) d a ys after last 
d ose of st u d y dr u g if E T. 
1 0) 
Bl o o d f or c h e mistr y will b e o btai n e d pre d ose o n d osi n g d a ys a n d f oll o w- u p d a ys ( 1 4, 5 6, a n d 8 4 [ ± 5] d a ys after t he last d ose of st u d y dr u g if E T).  
1 1) 
Bl o o d f or C B C wit h differe ntial will b e o btai n e d j ust pri or t o eac h S C i njecti o n, 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of eac h S C i njecti o n as well as o n all f oll o w- u p da ys 
( 1 4, 5 6, a n d 8 4 [ ± 5] d a ys after last d ose if E T).  
1 2) 
Bl o o d f or P K will b e o btai n e d pre d ose o n d osi n g d a ys a n d o n f oll o w- u p d a ys ( 1 4, 5 6, a n d 8 4 d a ys after t h e last d ose of st u d y dr u g if E T). 
1 3) 
Bl o o d f or A D A will b e c ollecte d pre d ose o n O L E d osi n g Da ys 1, 4 3, a n d 8 5 ( ± 5), o n f oll o w- u p O L E Da ys 9 9 a n d 1 6 9 ( 1 4 a n d 8 4 [ ± 5] d a ys after t he last d ose of st u d y dr u g if 
E T. T h e A D A sa m ple will als o b e c ollecte d a n y ti m e a n i m m u n o ge nicit y-relate d A E occ urs. 
1 4) 
Uri n e will b e c ollecte d f or di pstic k pre g na n c y test o n all d osi n g d a ys a n d f oll o w- u p d a ys ( 1 4, 2 8, 5 6, a n d 8 4 da ys after t h e last d ose of st u d y dr u g if E T) f or all s u bjects of 
c hil d beari n g p ote ntial. Test kits will b e s u p plie d b y t h e ce ntral la b orat or y. T ests will b e c o m plete d o n site a n d e v al u ate d pri or t o eac h S C i njecti o n. If t h e Da y 1 O L E visit 
d oes n ot occ ur o n Da y 9 9 of t he d o u ble- bli n d p eri o d, t h e n a di pstic k uri ne pre g n a n c y test will ha v e t o be d o n e. Da y 1 ca n occ ur u p t o 7 da ys after t h e Da y 9 9 visit of t h e 
d o u ble- bli n d peri o d. 
1 5) 
Uri n e f or sta n d ar d uri n al ysis will be o btai n e d o n O L E Da y 1 a n d f oll o w- u p Da ys 9 9 a n d 1 6 9 ( 1 4 a n d 8 4 d a ys [ ± 5] if E T) a n d s y m pt o m- b ase d, as n ecessar y. 
1 6) 
S u bjects will re mai n u n d er o bser v ati o n at t he site f or at least 1 h o ur after t h e e n d of eac h S C i njecti o n. I n t he e v e nt of a n I R R, t h e s u bject m a y re q uire pr ol o n ge d o bser v ati o n 
( > 1 h o ur or u ntil t h e s y m pt o ms res ol v e), as per t h e I n v esti gat or’s discreti o n. S u bjects will als o be i nstr u cte d t o i m me diatel y c o ntact t h e st u d y d o ct or if a n y reacti o ns o cc ur 
after disc har g e. 


Pr ot o c ol A K 0 0 2- 0 1 8 
A me n d m e nt 6 
Date: 0 8 Se pte m b er 2 0 2 3 
Alla k os I n c.
Pa g e 1 3 5 of 1 3 5
C o nfi d e nti al
T a ble 8 N otes c o nt. 
1 7) 
T h e ca pt ure of S A E, n o n-seri o us A E, a n d A E SI will b e ca pt ure d t hr o u g h t h e O L E p eri o d u ntil O L E Da y 1 6 9 or E T. A d v erse e v e nts will b e assesse d a n d rec or d e d i n t h e C R F 
of t he A K 0 0 2- 0 1 8 O L E p eri o d d ata b ase b e gi n ni n g fr o m t h e start of t h e first o p e n-la bel S C i njecti o n d uri n g t h e O L E Da y 1 visit. 

SAP_001.pdf: 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and 
Safety of Subcutaneous Lirentelimab in Adult Subjects with Moderate-to-Severe Atopic 
Dermatitis Inadequately Controlled by Topical Treatments 
NCT Number: NCT05155085 
Document Date: 18 September 2023 






 
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Table of Contents 
Statistical Analysis Plan for Protocol AK002-018.......................................................................1 
Signature Page ................................................................................................................................2 
Table of Contents ...........................................................................................................................3 
List of In-Text Tables ..............................................................................................................7 
List of Abbreviations ...............................................................................................................8 
Revision History ...........................................................................................................................10 
1. 
Introduction .........................................................................................................................11 
2. 
Study Objectives ..................................................................................................................11 
2.1 
Primary Objective and Endpoint ...............................................................................11 
2.1.1 Eczema Area and Severity Index (EASI) ......................................................11 
2.2 
Secondary Objectives and Endpoints ........................................................................12 
2.2.1 
 .......................................................12 
2.3 
Exploratory Objectives and Endpoints ......................................................................12 
2.3.1 
 ....................................................................13 
2.3.2 
 .............................................................13 
2.3.3 
 .......................................14 
2.3.4 
 ...................................................................14 
2.4 
Safety Objectives and Endpoints ...............................................................................14 
3. 
Study Design .........................................................................................................................14 
3.1 
General Description ...................................................................................................14 
3.2 
Methods of Assigning Subjects to Treatment Groups ...............................................22 
3.3 
Treatment Blinding ....................................................................................................22 
3.4 
Determination of Sample Size ...................................................................................22 
4. 
Definitions ............................................................................................................................23 


 
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4.1 
Terminology and Definitions ....................................................................................23 
4.2 
Target of Estimation ..................................................................................................23 
4.2.1 Population Targeted by the Scientific Question ............................................24 
4.2.2 Variables of Interest (or Endpoint) to be Obtained for Each Subject 
that is Required to Address the Scientific Question ......................................24 
4.2.3 Treatment .......................................................................................................24 
4.2.4 Intercurrent Events ........................................................................................24 
4.2.5 Strategy for Handling Intercurrent Events ....................................................24 
4.2.6 Summary Measure of the Estimand ..............................................................26 
5. 
Statistical Methods ..............................................................................................................26 
5.1 
General Methodology ................................................................................................26 
5.2 
Visit Window and Unscheduled Assessments ..........................................................27 
5.3 
Adjustment for Covariates .........................................................................................28 
5.4 
Data Handling Conventions ......................................................................................28 
5.5 
Independent Safety Monitoring and Interim Data Analysis ......................................28 
5.6 
Timing of Data Analyses ...........................................................................................28 
5.7 
Multicenter Study ......................................................................................................29 
5.8 
Multiple Comparisons/Multiplicity Adjustment .......................................................29 
6. 
Statistical Analysis ...............................................................................................................30 
6.1 
Analysis Populations .................................................................................................30 
6.1.1 Safety Population ...........................................................................................30 
6.1.2 Intent-to-Treat Population .............................................................................30 
6.1.3 Modified Intent-to-Treat Population .............................................................30 
6.1.4 Per Protocol Population .................................................................................31 
6.2 
Disposition of Subjects ..............................................................................................31 
6.3 
Protocol Deviations and Violations ...........................................................................31 


 
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6.4 
Demographics and Baseline Disease Characteristics ................................................32 
6.5 
Medical History .........................................................................................................32 
6.6 
Electrocardiogram .....................................................................................................32 
6.7 
Pregnancy Test ..........................................................................................................32 
6.8 
Treatments .................................................................................................................32 
6.8.1 Treatment Compliance ..................................................................................32 
6.8.2 Prior, Concomitant, and Newly Initiated Medications ..................................33 
6.9 
Analyses of Efficacy Endpoints ................................................................................33 
6.9.1 Analysis of Primary Efficacy Endpoint .........................................................34 
6.9.2 Analysis of Secondary Efficacy Endpoints ...................................................35 
6.10 
Analysis of Exploratory Endpoints ...........................................................................36 
6.10.1 Change from Baseline in 
 .....36 
6.10.2 Time to Onset of Response on 
 ............36 
6.10.3 
 Responder Rate ...................37 
6.10.4 Percent and Change from Baseline in 
 .37 
6.10.5 Change from Baseline in 
 ..............................................................37 
6.10.6 Change from Baseline in 
 .37 
6.10.7 Change from Baseline in 
 .....................................................................38 
6.10.8 Proportion of Subjects who Achieve Improvement from Baseline in 
 .38 
6.10.9 Change from baseline in 
 ..........................................................38 
6.10.10 Change from Baseline in 
 ............38 
6.11 
Analysis of Pharmacokinetic Endpoint .....................................................................40 
6.12 
Safety Analyses .........................................................................................................40 
6.12.1 Adverse Events ..............................................................................................40 
6.12.2 Laboratory Test .............................................................................................41 
6.12.3 Vital Signs, Height and Weight, and Other Safety Measures .......................42 


 
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6.12.4 Electrocardiogram .........................................................................................42 
6.12.5 Physical Examination ....................................................................................42 
6.12.6 Analysis of Anti-Drug Antibodies .................................................................42 
7. 
Validation .............................................................................................................................42 
8. 
References ............................................................................................................................43 
9. 
Appendices ...........................................................................................................................44 
9.1 
Appendix 1: Intercurrent Events and Definitions of Prohibited Medication Use and 
Rescue Medication/Treatment for AD Symptoms ....................................................45 
9.2 
Appendix 2: List of Tables, Figures, and Listings ....................................................48 
 


 
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List of In-Text Tables 
Table 1 
Schedule of Assessments .......................................................................................17 
Table 2 
Terminology and Definitions .................................................................................23 
Table 3 
 ..............................................................38 
Table 4 
Meaning of 
 ............................................39 
Table 5 
 ...............................................................39 
 


 
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List of Abbreviations 
AD 
Atopic dermatitis 
ADA 
Anti-drug antibody 
ADaM 
Analysis Data Model  
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
ATC 
Anatomical Therapeutic Chemical (Classification System) 
BLOQ 
Below limit of quantification 
BMI 
Body mass index  
CBC 
Complete blood count 
CDISC 
Clinical Data Interchange Standards Consortium 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CSR 
Clinical study report 
DM 
Data management  
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture (system) 
ET 
Early Termination 
FDA 
Food and Drug Administration 
ICE 
Intercurrent events  
ICH 
International Conference on Harmonization 
ICF 
Informed Consent Form 
IRT 
Interactive Response Technology 
ITT 
Intent-to-treat (population) 
LLN 
Lower limit of normal 
LLOQ 
Lower limit of quantification 
LSM 
Least squares mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat (population) 
MMRM 
Mixed Model for Repeated Measures 
NRI 
Non-responder Imputation 


 
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p-value 
Probability value 
PD 
Pharmacodynamics 
PE 
Physical examination 
PK 
Pharmacokinetic(s) 
PP 
Per protocol (population) 
PT 
Preferred term 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical analysis system 
SC 
Subcutaneous 
SD 
Standard deviation 
SE 
Standard error(s) 
SDTM 
Study Data Tabulation Model 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event(s) 
TEAESI 
Treatment-emergent adverse event(s) of special interest 
TESAE 
Treatment-emergent serious adverse event(s) 
TLF 
Tables, listings, and figures 
ULN 
Upper limit of normal 
WHO 
World Health Organization 
WHODD 
World Health Organization Drug Dictionary 
 


 
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Revision History 
Version Date 
Version 
Number 
Description 
25 July 2023 
1 
Initial document 
18 September 2023
2 
Amendment 1 
 
 
 
 


 
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1. 
Introduction 
Lirentelimab (AK002) Subcutaneous (SC) is being studied in subjects with moderate-to-severe 
atopic dermatitis inadequately controlled by topical treatments. Atopic dermatitis (AD) is a 
chronic pruritic inflammatory dermatitis that affects approximately 16.5 million (7.3%) adults in 
the US, of which around 6.6 million (40%) have moderate-to-severe disease.  
The statistical analysis plan (SAP) describes a priori the data and variables to be summarized or 
analyzed, including specifications of the analytical methods to be performed. This SAP 
supersedes the statistical analysis methods described in the clinical protocol except for the 
standard pharmacokinetic (PK) data analyses. Significant deviations/changes from the planned 
analyses described in this SAP will be identified, with justification, in the appropriate section of 
the clinical study report (CSR). The SAP is based on Clinical Study Protocol AK002-018 
Amendment 6, dated 08 September 2023, and the associated electronic case report form (eCRF).  
2. 
Study Objectives  
2.1 
Primary Objective and Endpoint 
The primary objective of the study is to assess the efficacy of lirentelimab SC in subjects with 
moderate-to-severe AD as assessed by the difference in the proportion of subjects who achieve at 
least 75 percent improvement from baseline in the Eczema Area and Severity Index (EASI-75) at 
Week 14 when compared with placebo.  
In particular, the associated estimand for this objective is to measure the effect of therapy with 
lirentelimab SC as assessed by the proportion of subjects with EASI-75 response at Week 14 
assuming treatment response disappears after subjects are rescued or discontinue from the study 
or treatment. See Sections 4.2.5 and 6.9.1 on how this estimand handles outcomes after the 
occurrence of any intercurrent event through non-responder imputation (NRI). 
2.1.1 
Eczema Area and Severity Index (EASI) 
The EASI score is a tool used to measure the extent (area) and severity of atopic dermatitis with 
respect to erythema, excoriation, induration, and lichenification over the 4 anatomic regions of 
the body: lower and upper extremities, trunk, and head. The total EASI score will be in a range 
from 0 to 72 points (from no disease to maximum disease severity) and the assessment is 
conducted by the Investigator. An EASI score of 16 during screening is required to enroll in the 
study. The EASI will be determined by Investigators at the scheduled and unscheduled clinic 
visits according to Table 1. 


 
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Enrollment will be monitored to limit the impact of randomizing a disproportionately large 
number of subjects with an EASI score in the lower range, reflecting more moderate disease only 
(i.e., EASI score < 22). This will also provide a subject population with a full range of EASI 
scores consistent with the intent to study lirentelimab in moderate-to-severe AD disease. 
2.2 
Secondary Objectives and Endpoints 
The secondary objectives are to characterize further the efficacy of lirentelimab SC in subjects 
with moderate-to-severe AD as measured by:  
 
Percent change in EASI from baseline to Week 14 
 
Proportion of subjects with IGA of 0 or 1 and a 2-point improvement at Week 14 compared 
with baseline 
2.2.1 
Global Assessment (IGA) 
The Investigator  Global Assessment (IGA) is a 5-point scale that provides a global clinical 
assessment of AD severity ranging from 0 to 4 and assesses disease severity and clinical 
response using a 5-point scale: 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; and 
4 = severe. The score is determined by ranking the extent of erythema and papulation/infiltration. 
A decrease in score relates to an improvement in signs and symptoms. The IGA will be 
determined by Investigators at the scheduled and unscheduled clinic visits according to Table 1.  
2.3 
Exploratory Objectives and Endpoints 
The exploratory objectives are to evaluate the effect of lirentelimab SC in subjects with 
moderate-to-severe AD for the following parameters:  
 
Change in 
 
 at Week 14. 
 
Time to onset of response on the 
, where 
response is defined as improvement (at least a 
 reduction from baseline) of weekly 
average of daily 
 during the 14-week treatment period. The analysis will be based on 
subjects with a baseline 
 
 
Change from baseline to Week 14 in 
. 
 
Pharmacodynamics (PD) of lirentelimab SC in subjects with AD as measured by changes 
from baseline in 
 
 
Other indices of efficacy of lirentelimab SC in subjects with AD. Changes in signs and 
symptoms (compared to baseline) between lirentelimab SC and placebo will be measured 
by: 


 
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 Change from baseline to Week 14 in 
 
 Change in 
 from baseline to Week 14 
 Proportion of subjects who achieve 
 
 
 Proportion of subjects who achieve 
 
 
 Change from baseline to Week 14 in 
  
 Change from baseline to Week 14 in 
  
 Change from baseline over time in 
  
2.3.1 
 
The 
 is a clinical tool used to determine the 
. 
The 
 tool was developed by the 
 as a 
measure of 
. It includes assessment of the 
 by the Investigator in 
addition to patient-reported symptoms. Subjective assessment of 
 is recorded for 
each symptom by the patient on a 
 where 
 and 
 
. Total score ranges from 
 
. During screening, 
 will be determined, and a baseline will be established. In 
addition, 
 will also be determined predose on all dosing days and during follow-up on 
Days 99, 141, and 169 or ET. 
2.3.2 
 
The 
 is a validated 
, patient reported outcome (PRO) of 
 
 that will be completed by the subject on a daily basis, at approximately the same time 
every day. On dosing days, 
 should be completed while subject is at the site. 
During screening, 
 will be determined, and a baseline will be established. The 
 rating 
-hour period. The following question 
will be presented to subjects: 
Scale of 
 


 
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2.3.3 
 
The 
 is a simple measurement of the 
. At 
screening, the Investigator will determine the 
. The subject is 
 
 will be 
determined by the Investigator during screening, predose on all dosing days, and during follow-
up on Days 99, 141, and 169 or ET. 
2.3.4 
 
The 
 is a 
 questionnaire used to measure the impact of 
 
 of an affected person. The format is a simple response 
that assess 
 over the past week with an overall scoring 
system of 
 a high score is indicative of a 
 is a self-
administered- questionnaire. Subjects will complete this during screening, predose on all dosing 
days, and during follow-up on Days 99, 141, and 169 or ET. 
2.4 
Safety Objectives and Endpoints 
The safety objective of the study is to evaluate the study drug safety profile using the following 
safety endpoints:  
 
Treatment emergent adverse events (TEAE) including severity, relationship to study 
treatment, serious adverse events (SAE), and adverse events (AE) leading to study drug 
withdrawal 
 
Anti-drug (AK002) antibody (ADA)  
 
Changes in Laboratory tests 
 
Changes in Physical examination  
 
Changes in vital signs  
3. 
Study Design 
3.1 
General Description 
This Phase 2, proof-of-concept, randomized, double-blind, placebo-controlled study will 
investigate the efficacy and safety of lirentelimab SC in adult subjects with moderate-to-severe 
AD inadequately controlled by topical treatments. Approximately 130 subjects will be enrolled 
in approximately 70 sites in the US and Germany and will be randomized 1:1 to receive either 7 
SC injections of placebo or lirentelimab and then followed for 12 weeks after the last dose. 
Subjects will be given the option to enroll into an open-label extension (OLE) period of the study 
after completing the Day 99 visit of the double-blind period. Subjects choosing not to enter the 


 
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OLE period will continue to be followed in the double-blind period of the study for 12 weeks 
after the last dose. 
Based on the feedback from atopic dermatitis experts and completed feasibility assessments, it is 
expected that each site will be able to screen three subjects and enroll two of them in the duration 
of the enrollment period. Enrollment is competitive, and to ensure the enrollment goal is 
achieved in a timely manner, approximately 70 sites (approximately 55 in the US and 
approximately 15 in Germany) will be initiated. If study enrollment rate can be achieved with 
fewer sites to meet the study timeline, then fewer sites may be needed. 
Subjects will be consented and screened, and those who meet eligibility criteria can be enrolled 
in the study. Subjects who do not meet all eligibility criteria at screening or who qualify at 
screening but are not enrolled may be assigned a new patient identification number and 
rescreened once. Subjects rescreened within 30 days of signing the initial informed consent form 
(ICF) will not need to sign a new ICF if there have been no changes to the ICF. 
Subjects will be screened for approximately 2 weeks (-14 days) prior to dose administration. 
During screening and through various time points during the study, the EASI, IGA, BSA, peak 
pruritus Numeric Rating Scale (ppNRS), Scoring Atopic Dermatitis Index (SCORAD), and 
Dermatology Life Quality Index (DLQI) assessments will be completed. Additional questions 
will be asked about symptoms related to asthma, allergic rhinitis, and allergic conjunctivitis that 
subjects with the atopic condition(s) may have on Day 1, Day 99, and OLE Day 99 (Atopic 
Conditions Questionnaire). 
Certain medications are prohibited during the study. Use of systemic and/or topical 
corticosteroids, calcineurin inhibitors, JAK inhibitors, topical PDE4 inhibitors (crisaborole), 
dupilumab, or tralokinumab are prohibited during the study. Subjects who are on any topical 
corticosteroids, topical calcineurin inhibitors, topical JAK inhibitors, or PDE4 inhibitors at the 
time of screening must discontinue these at the first screening visit. 
Biologics or medications that may interfere with the study safety or efficacy assessments such as 
systemic immunosuppressive or immunomodulatory drugs or biologics and systemic 
corticosteroids must be discontinued prior to the first screening visit and are prohibited 
throughout the study. 
During the last 7 days prior to Day 1 (the first day of study drug dosing), the subject must have 
used, at least twice daily, only non-medicated topical therapy (i.e., emollient) without other 
active ingredients indicated to treat AD or other additives, which could affect AD (e.g., 
hyaluronic acid, urea, ceramide, or filaggrin degradation products). If a subject is not using any 


 
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emollient at the time of screening, a suitable non-medicated, non-prescription emollient will be 
recommended by the Investigator. 
Eligible subjects who meet selection criteria at screening and at baseline will receive the first 
dose of lirentelimab SC or placebo SC on Day 1. Subjects will receive 6 more doses on Days 15, 
29, 43, 57, 71, and 85. 
Subjects will be given the option of entering an OLE period of the study after completing the 
Day 99 visit of the double-blind period of the study, contingent on meeting defined study 
selection criteria. Subjects not entering the OLE period will be followed for 12 weeks after the 
last dose in the double-blind period.  
The primary endpoint will be assessed at Week 14, i.e., 2 weeks following the last dose in the 
double-blind period of the study. 
Randomization will be stratified based on IGA 3 vs. 4 and on biologic status as it pertains to 
previous treatment of atopic dermatitis, naïve vs. exposed. Approximately 40% of the study 
population will be subjects with an IGA of 4. 
Fresh biopsies of lesional and non-lesional skin may be collected from subjects predose and post-
dose at selected US sites. Providing biopsies is optional, and subjects will sign a separate consent 
form for biopsy collection. 
The overall schedule of procedures and assessments are presented in Table 1. 
 






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ADA: Anti-lirentelimab antibody 
EOS: End of Study  
IRT: 
Interactive Response Technology 
 
  
FSH: Follicle-Stimulating Hormone  
PK: 
Pharmacokinetics 
CBC: Complete Blood Count  
hCG: Human Chorionic Gonadotropin  
 
  
  
IgE: Immunoglobulin E 
  
EASI: Eczema Area and Severity Index 
IP: 
Investigational Product  
vIGA: 
Validated 
 
ECG: Electrocardiogram 
 
Table 1 Notes 
1) Dose 1 is the day of the first SC injection. Dose 1/Day 1 can occur within a ±3 day window, i.e., the screening period can be a maximum of 17 days and a minimum of 
11 days. Dosing visits must be conducted within the ± windows stipulated in the protocol. 
2) The EOS visits should be conducted 14, 56, and 84 (±5) days after the last dose of study drug or prior to this, if necessary, to ensure compliance with the visit. If the EOS visit 
occurs more than 56 days after the last dose of study drug, then perform the visit as soon as possible. The procedures listed under the 14-day post-study drug visit will be 
conducted unless otherwise directed by the Medical Monitor. For subjects participating in the OLE period, AE and concomitant medications should be collected and recorded 
in the AK002-018 double blind treatment period database up until the start of the first open-label SC injection after the Day 99 visit. 
3) Documentation of AD diagnosis and previous treatments should be noted in detail. This can be subject reported and/or based on medical records (details in protocol Section 
12.2.6). 
4) At screening, height (in cm) and weight (in kg) will be recorded. Body weight will be measured at every visit. 
5) Vital signs will be measured at every visit. On all dosing days: within 30 minutes predose, 15 (±5) minutes after administration of study drug SC injection, and just prior to 
jection-related reaction (IRR) occurs. Vital signs including systolic and 
diastolic blood pressure, pulse, body temperature, and respiratory rate will be measured after the subject has been at rest f
obtained (unless collected for an IRR). 
6) A 10-lead or 12-
5 minutes. 
7) A complete physical examination will be performed by either the Investigator or designee and include the following body system or organ assessments: skin; head, eyes, ears, 
nose, and throat; thyroid; lungs; cardiovascular; abdomen; extremities; lymph nodes; and a brief neurological examination. A symptom-directed physical exam (including 
assessment of possible injection site reactions) will be performed by the Investigator or designee, as needed, if any symptoms are reported. 
8) Activate PRO questionnaire and provide subject with unique username and password. PRO questionnaire should be activated for all subjects on screening Day 1. 
9) During screening, vIGA, EASI, 
 will be determined, and a baseline will be established. vIGA, EASI, 
 must be 
completed predose on dosing days. To ensure there is sufficient PRO data at baseline, a subject should complete at least four daily PRO questionnaires per week for a 
minimum period of the seven days prior to Day 1. 


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Table 1 Notes cont. 
10) Subjects will be prompted to answer additional questions about symptoms related to asthma, allergic rhinitis, and allergic conjunctivitis (Atopic Conditions Questionnaire). 
11) Blood samples for total serum IgE will be collected during screening, predose on Days 57 and 85, on follow-up Days 99, 141, and 169, or 14, 56, and 84 (±5) days after the 
last dose of study drug if early termination (ET). 
12) Blood for serology testing will be collected during screening and will include HBsAg, hepatitis C antibody, anti-HBc, and HIV. 
13) Female subjects of childbearing potential are required to have hCG measured. Postmenopausal women are required to have FSH me
negative serum hCG will be required during the screening period in order for subject to proceed to randomization. Blood for chemistry will be obtained predose on dosing 
days and follow-up days (14, 56, and 84 [±5] days after the last dose of study drug if ET).  
14) Blood for CBC with differential, including absolute blood eosinophil count, will be obtained at screening, just prior to each SC injection, 1 hour (±15 minutes) after the end of 
each SC injection, and on all follow-up days (14, 56, and 84 [±5] days after last dose if ET). All differential blood counts from Day 1 (post-dose) through the end of the 
-blind period will be blinded to the Sponsor and the site. An unscheduled CBC may be collected at the request of the Safety Monitor. 
15) Blood for PK will be obtained predose on all dosing days as well as on Day 8 (±3) and on follow-up days (14, 56 and 84 [±5] days after last dose of study drug if ET).  
16) Blood for ADA will be collected predose on dosing Days 1, 43, and 85 (±5), as well as on Day 8 (±3), and on follow-up Days 99 and 169 (14 and 84 [±5] days after last dose 
of study drug if ET). The ADA sample will also be collected any time an immunogenicity-related AE occurs. 
17) Urine will be collected for dipstick pregnancy test on all dosing days, Day 8, and all follow-up days (14, 56, and 84 days after last dose of study drug if ET) for all subjects of 
childbearing potential. Test kits will be supplied by the central laboratory. Tests will be completed on site and evaluated prior to each SC injection. 
18) Urine for standard urinalysis will be obtained at screening and on follow-up Days 99 and 169 (14 and 84 days [±5] if ET), and symptom-based, as necessary. 
19) Randomization will be conducted through the IRT system. Subjects will be randomized 1:1, lirentelimab SC 300 mg or placebo SC. They will be stratified based on biologic 
status and IGA score at baseline. 
20) The capture of non-serious AE and adverse events of special interest (AESI) will begin after the first dose of study drug has occurred. 
21) The reporting of serious adverse events (SAE) occurring after signing the ICF and prior to the first SC injection will be limited to those that relate to screening procedures. The 
capture of all SAE and AE that are not related to screening procedures will begin at the time of first SC injection of study drug. For subjects participating in the OLE period, 
AE will be assessed and recorded in the CRF of the AK002-018 double-blind treatment period database up until the start of the first OLE SC injection, after the Day 99 visit. 
The AE will be recorded in the CRF of the AK002-018 OLE period database beginning with the start of the first open-label SC injection after Day 99. 
22) Lesional and non-lesional biopsies will be collected at selected US sites and only for subjects who consent to this optional procedure. Biopsies may be collected at baseline 
predose on Day 1 and again on Day 99/Week 14. See Section 12.1.10 of the protocol. 
 


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Table 1 Notes cont. 
23) Open-label extension dosing may start on Day 99 after all Day 99 procedures are conducted or within 7 days after the Day 99 visit. Subjects who decide to enter the OLE 
period and meet the selection criteria for the OLE period, will follow the schedule of events in Appendix 11 of the protocol and do not need to repeat Day 99 procedures if 
OLE Day 1 visit is completed on the same day as Day 99 visit. 


 
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3.2 
Methods of Assigning Subjects to Treatment Groups 
Approximately 130 subjects with moderate-to-severe AD inadequately controlled by topical 
treatments will be randomized to lirentelimab SC, or placebo in a 1:1 ratio. Stratified permuted 
block randomization will be used. Randomization will be stratified based on IGA 3 vs. 4 and on 
biologic status, naïve vs. exposed. Approximately 40% of the study population will be subjects 
with an IGA of 4. An Interactive Response Technology System (IRT) will be used to perform the 
randomization. 
3.3 
Treatment Blinding 
This is a double-blind study. The identity of active and placebo treatments will not be known to 
Investigators, Sponsor (including safety monitor), research staff (including pharmacy), subjects, 
or the study monitor.  
3.4 
Determination of Sample Size 
It is hypothesized that the percentage of subjects who achieve EASI 75 at Week 14 are 44% and 
15% for lirentelimab SC and placebo SC, respectively.  
To detect a treatment difference of 29%, the number of subjects required for 90% power is 55. 
However, to account for an anticipated 10% dropout rate, the sample size will be increased to 65 
per treatment group.  
Enrollment will be monitored to limit the impact of randomizing a disproportionately large 
number of subjects with an EASI score in the lower range, reflecting more moderate disease only 
(i.e., EASI score <22). This will also provide a subject population with a full range of EASI 
scores consistent with the intent to study lirentelimab in moderate-to-severe AD disease. 
 
 


 
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4. 
Definitions  
4.1 
Terminology and Definitions 
Table 2 
Terminology and Definitions  
Terminology 
Definition 
Baseline 
Baseline for non-daily assessment (e.g., laboratory tests) is defined as 
the non-missing value collected most recently to and before the time 
of the very first dose of study drug. Baseline Patient Reported 
Outcome (PRO) data will be the average of the weekly PRO data 
collected in the last 7 days prior to Day 1. 
Concomitant 
Medications and 
Procedures 
Medications and procedures with a stop date before the treatment 
dosing date will be considered prior medications/procedures. 
Medications/procedures with a start or stop date on or after the 
treatment dosing date will be considered concomitant. All 
medications/procedures marked as ongoing are concomitant. 
Study Day  
Study Day 1 is defined as the date on which a subject received the 
first dose of study drug. For visits prior to the first dose of study drug, 
Study Day is calculated as Visit Date  Day 1 Date. For visits after 
the first dose, Study Day is calculated as Visit Date  Day 1 Date +1. 
Study Week 
Study Week for PRO analysis is defined as 7 days a week starting 
from the day of first dose (Day 1).  
 
4.2 
Target of Estimation 
The estimand for the AK002-018 study estimates the effect of treatment, while considering 
treatment adherence and response. The estimand will provide an answer to the question that is 
without adding any further drugs or exit the study prematurely, what improvement can I expect 
at 14 weeks
  
The sections below describe the attributes of the estimand consistent with the ICH E9 (R1) 
Addendum (FDA, 2021). 


 
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4.2.1 
Population Targeted by the Scientific Question 
The population targeted by the scientific question is defined via the inclusion and exclusion 
criteria as part of the study protocol. Subjects may be male or female and must have a clinical 
diagnosis of moderate-to-severe AD inadequately controlled by topical treatments of sufficient 
duration within the 6-month period prior to study entry as defined by the study inclusion criteria. 
4.2.2 
Variables of Interest (or Endpoint) to be Obtained for Each Subject 
that is Required to Address the Scientific Question 
The primary endpoint is the proportion of subjects who achieved EASI-75 in Week 14.  
4.2.3 
Treatment 
Lirentelimab SC or placebo SC administered to subjects on Days 1, 15, 29, 43, 57, 71, and 85. 
4.2.4 
Intercurrent Events 
The events below are considered intercurrent events (ICE) confounding with the efficacy 
outcomes. 
 
Premature discontinuation from the double-blind portion of the study  
 
Use of prohibited medications during the study 
 
Use of rescue medication for symptoms of AD 
4.2.5 
Strategy for Handling Intercurrent Events 
For subjects who experienced an ICE of premature discontinuation from the double-blind portion 
non-responder
be set to missing for continuous endpoints from the point when that ICE occurs. An appropriate 
method for handling missing data through statistical modeling (e.g., multiple imputation [MI]) 
will be used. 
For subjects that take prohibited medications during the double-blind portion of the study (see 
Appendix 1: Intercurrent Events and Definitions of Prohibited Medication Use and Rescue 
Medication/Treatment for AD Symptoms) for medically necessary reasons other than alleviating 
AD symptoms, the efficacy data will be handled as follows: 
 
The use of topical corticosteroids, topical calcineurin inhibitors, topical JAK inhibitors, 
topical PDE4 inhibitors or other prohibited topical medications for reasons other than for 
the treatment of AD for 5 or more days will result in all subsequent efficacy data being 
censored for purposes of analysis from the time of initiation of the prohibited therapy 
onwards. Use of prohibited topical therapies for a duration of less than 5 days will result in 


 
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all subsequent efficacy data being censored for purposes of analysis from the time of 
initiation of the prohibited therapy onwards only if the treatment occurs within 7 days of the 
Day 99 visit. 
 
The use of systemic corticosteroids for periods of 3 or more days or the use of depot 
injectable steroids for medical reasons other than the treatment of AD will result in all 
subsequent efficacy data being censored for purposes of analysis from the time of initiation 
of the prohibited therapy onwards. Use of systemic corticosteroids for a duration of less 
than 3 days will result in all subsequent efficacy data being censored for purposes of 
analysis from the time of initiation of the prohibited therapy onwards if the treatment occurs 
within 28 days of the Day 99 visit. 
 
The use of any other systemic immunomodulator (including JAK inhibitors), 
immunosuppressant or biologic therapy during the course of the study for the purpose of 
treating a medical condition other than AD will result in censoring of all efficacy data from 
the time of initiation of the prohibited therapy onwards.  
When applicable, the censoring rule will censor data after a subject experiences an ICE. This 
censoring rule is equivalent to using all the data up to the date of an ICE.  
For subjects that take prohibited medications during the double-blind portion of the study (see 
Appendix 1: Intercurrent Events and Definitions of Prohibited Medication Use and Rescue 
Medication/Treatment for AD Symptoms) described as either rescue therapy or taken for the 
purpose of alleviating AD symptoms the efficacy data will be handled as follows: 
The use of rescue therapy for the treatment of AD symptoms defined as either 1) use of topical 
corticosteroids, topical calcineurin inhibitors, JAK inhibitors, topical PDE4 inhibitors or other 
prohibited topical therapies at any point in the study, 2) the use of phototherapy for AD, 3) the 
use of systemic corticosteroids (including injectables) for the treatment of AD or 4) the use of 
any systemic immunomodulator (including JAK inhibitors), immunosuppressant or biologic 
therapy at any point in the study will result in that subject being considered as having an ICE and 
efficacy data will be imputed as a non-responder from the time of initiation of the rescue therapy 
onwards.  
Blinded adjudication of all potential ICE due to either prohibited medication use for any medical 
reason or use of rescue medications for symptoms of AD will be implemented before database 
locks. 


 
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4.2.6 
Summary Measure of the Estimand 
Percent (and 95% CI) of subjects achieving EASI-75 at Week 14 in the lirentelimab SC and 
Placebo treatment groups and the absolute difference (and 95% CI) in the percent response 
between treatments. 
5. 
Statistical Methods 
5.1 
General Methodology  
All statistical analyses will be conducted using SAS v9.4 or later version on the Microsoft 
Windows Operating System.  
All eCRF data (raw data) will be converted into SDTM (Study Data Tabulation Model) datasets, 
which will be used to create ADaM (Analysis Data Model) data sets. The creation of the SDTM 
and ADaM data sets will follow the CDISC (Clinical Data Interchange Standards Consortium) 
standards and the FDA Study Data Technical Conformance Guide. All analysis tables and 
listings will be created from the ADaM data sets. 
Continuous data will be summarized using n  (number of subjects with non-missing 
observations), mean, median, standard deviation (SD), minimum value, and maximum value. 
Categorical data will be summarized using the frequency count and percentage (n, %) of subjects 
in each category. Number of subjects with non-missing values or number of subjects with 
missing values (e.g., Not Done) will be presented, where appropriate. Subjects with missing 
values will not contribute to the denominator for percentage calculations, unless specified 
otherwise. Counts of 0 in any category will be presented without percentage. All summaries will 
be presented for individual treatment groups. In addition, for summary of disposition and subject 
baseline characteristics, the presentation will include both treatment groups combined.  
The precision rules for the presentation of summary statistics will be: 
 
Sample size (n, N) and number of missing responses (if displayed): Integer 
 
Mean, confidence interval, and median: Same number of decimal places as 
reported/collected 
 
Standard deviation: Same number of decimal places as reported/collected 
 
Percentiles, minimum, maximum: Same number of decimal places as reported/collected 
 
Odds Ratio: 2 decimal places 


 
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Percentage: 1 decimal place generally, or 2 decimal places for <0.1%, or no decimal places 
 
 
P-value: 4 decimal places 
 
WBC: 2 decimal places as 0.01 × 109/L 
 
Height/Weight/BMI: 1 decimal place 
The data summaries will be accompanied by individual subject data listings. All data available 
from questionnaires, eCRF, and external transfer (labs) will be listed and will include relevant 
subject information, e.g., treatment group and study day. The listings will be sorted in the order 
of treatment group, subject ID, assessment name and date/time.  
Dates will be presented in the ISO-8601 format YYYY-MM-DD. Times will be displayed in 
24-hour clock format. Numbering for tables, figures and listings will follow ICH E3 Guideline 
(ICH, 1996). 
Alternative methods of analysis of the data may be considered prior to database lock, and reason 
for departure from the planned methods will be documented in an amendment to the SAP or in 
the CSR. 
5.2 
Visit Window and Unscheduled Assessments 
Data collected for study assessments provide information on the status of the subject at a given 
time point. Assessments will be slotted into analysis windows to allow summaries to be 
performed for subjects with similar study drug exposure. The analysis windows are described in 
Table 1 by the target study days (see Table 2) of the planned visits. For example, for visit 
description Day 8, the window is ±3 days of the visit description. 
In the event of multiple values from unscheduled or early termination assessments within a 
single analysis window, the value closest to the scheduled visit target study day will be used for 
analyses. If 2 values tie as closest to the time point (for example, 1 value is before and the other 
value is after the time point), then the later value will be selected. Data collected at all visits will 
be included in the data listings with visit presented as reported by the site. 
eDiary daily results (ppNRS) will be summarized by Study Week as outlined in Table 2. 


 
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5.3 
Adjustment for Covariates 
Efficacy analyses will be adjusted for baseline values and randomization strata using ANCOVA, 
MMRM, or Cochran-Mantel-Haenszel tests, where applicable.  
5.4 
Data Handling Conventions 
This section includes the methods for missing data imputation for some summary analyses, if 
necessary. 
Adverse events with incomplete start or stop dates (i.e., either day or month is missing) will be 
considered treatment-emergent adverse events (TEAE) unless the partial start date or the stop 
date confirms the AE started or ended prior to Study Day 1 (e.g., the day of the AE start date is 
unknown but the month and year indicate that the AE starts prior to Study Day 1). Adverse 
events with missing relationship to study drug 
summary tables and footnoted. Adverse events with missing severity will not be included in the 
by-severity summary table but will be footnoted in the table. 
When there is incomplete information regarding dosing dates for prior and concomitant 
medication, the medication will be considered as a concomitant medication unless it contradicts 
with the stop date. For example, a medication will be considered a prior medication if the month 
and year of the end date indicates a date before Study Day 1 even though the start date could be 
missing.  
5.5 
Independent Safety Monitoring and Interim Data Analysis 
An independent Data Monitoring Committee (iDMC) has been convened for this study. The 
iDMC will meet at established intervals (as per the iDMC charter) throughout the study and will 
also convene as necessitated by data and/or safety reviews.  
No interim analysis will be conducted for this study. 
5.6 
Timing of Data Analyses 
The database lock will occur after all 
 complete participation in the double-blind period 
of the study.  
For the database lock, applicable EDC data will be locked to protect write access after the 
following preconditions are fulfilled: 
 
All records are entered in the database. 
 
All AE are coded to the satisfaction of the Chief Medical Officer. 


 
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All medications are coded to the satisfaction of the Chief Medical Officer. 
 
All data queries have been resolved.  
 
All decisions have been made regarding all protocol violations and ITT population 
exclusions. 
 
Written authorizations to lock the database are obtained from Allakos Clinical Data 
Management and the Chief Medical Officer.  
The randomization code for this study will not be revealed until the previous preconditions are 
fulfilled, and documentation of the database lock is complete. After the database lock, the 
randomization code will be made available to individuals at Allakos who are involved in the data 
analysis. Data analysis will commence after the data lock. In addition, the PK and ADA data 
may be locked and assessed separately. 
5.7 
Multicenter Study 
The study will have approximately 70 sites in the US and Germany. For efficacy analysis, sites 
within countries will be pooled together. 
5.8 
Multiple Comparisons/Multiplicity Adjustment 
To control for the family-wise type-I error rate, the following testing procedures will be 
implemented: 
Test primary efficacy endpoint at 2-sided =0.05 level.  
 
If p 0.05 for primary endpoint, then reject the null hypothesis that lirentelimab SC is no 
different from placebo and accept the alternative hypothesis that lirentelimab SC is superior 
to placebo in improving EASI score.  
 
If 
y endpoint, the hypothesis tests for the secondary endpoints will 
proceed in the prespecified order (see Section 2.2). If at any point during the analysis of the 
secondary endpoints, the statistical test is not significant at 2-
hypothesis testing procedure will stop. Lirentelimab SC will be deemed superior to placebo 
for all endpoints prior to the stop. 
5.9 
Examination of Subgroups 
Key endpoints will be summarized by subgroup to assess the consistency of the treatment effect 
across each of these subgroups. For any subgroup, if there are zero subjects within a stratification 
stratum in any treatment group, the statistical model will not be adjusted by the stratification 
factors. Subgroups to be considered are: 


 
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Sex (Male, Female) 
 
Age group (<65, 65) 
 
Race (White, Non-White) 
 
Age of disease onset (<18 years, 18 years) 
 
Baseline disease severity index [moderate (IGA=3) and severe (IGA=4)] 
 
Baseline EASI severity index [moderate (EASI score <22) and severe (EASI score 22)] 
 
Body Surface Area (BSA) (
- <16
16%-<40%
40%) 
 
Prior biologics experience for the treatment of atopic dermatitis (biologic-naïve and 
biologic-exposed) 
6. 
Statistical Analysis 
6.1 
Analysis Populations 
screened subject
comprises subjects who signed the informed consent 
(ICF). 
6.1.1 
Safety Population 
The safety population comprises randomized subjects who have received at least 1 dose of the 
study drug.  
6.1.2 
Intent-to-Treat Population 
The intent-to-treat (ITT) population is defined as subjects who were randomized to treatment. 
6.1.3 
Modified Intent-to-Treat Population 
The modified intent-to-treat (mITT) population will be defined as all randomized subjects who 
received at least one SC injection of study drug and had no major protocol violations based on 
key inclusion and exclusion criteria defining the population of interest (i.e., defined as not 
meeting any of the key inclusion criteria number 3, 4, 6, 7, 8 or meeting exclusion criteria 
number 8 in this study). 
To assess the impact of excluding subjects from the efficacy analyses, results including all 
subjects (this population will be referred to as All Subjects All Data) and excluding the subjects 
who had any major protocol violation based on key inclusion and exclusion criteria defining the 
population of interest will be presented. The differences between these results will be noted, and 
the impact of such differences will be discussed in the clinical study report. 


 
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6.1.4 
Per Protocol Population 
The per protocol (PP) population will include the subjects in the mITT population who do not 
have any major protocol deviations or violations and who receive all 7 injections of study drug 
(see Section 6.3 for list of protocol deviations and violations).  
6.2 
Disposition of Subjects 
Subject demographics and reasons for screening failure will be summarized for screen-failed 
subjects. Subjects (n and %) who completed or discontinued from the study will be tabulated by 
treatment group and for both treatment groups combined. The primary reasons for study 
discontinuation will be included in the tabulation. The primary reasons may include, but are not 
limited to, any of the following: 
 
Subject withdrew consent 
 
Lost to follow-up 
 
Administrative reason 
 
Adverse event  
 
Investigator decision 
 
Failure to follow required study procedures 
 
Other 
Subject disposition will be summarized for the ITT population. Subject counts for the Safety, 
mITT, and PP populations will be included in the table. A data listing for subject disposition will 
be presented for the ITT population.  
6.3 
Protocol Deviations and Violations 
Protocol deviations will include, but are not limited to 
 
Non-compliance with scheduled study visit  
 
Non-compliance with study treatment  
 
Received prohibited medications (see Protocol Section 8.5) 
 
Any major violations of efficacy-related entry inclusion or exclusion criteria (defined as not 
meeting inclusion criteria number 3, 4, 6, 7, 8 or meeting exclusion criteria number 8)  
 
Non-compliance with study assessment procedures  
Subjects with major protocol deviations will be listed. The listing will include a brief description 
of the deviation, deviation category, and if applicable, study day when deviation occurred along 


 
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with other pertinent information. If warranted by the sample size, subjects (n and %) with major 
protocol deviations will be tabulated by treatment group and by deviation category. 
Subjects who are excluded from the mITT and PP population will be listed with reasons for 
exclusion.  
6.4 
Demographics and Baseline Disease Characteristics 
The following demographic and baseline characteristics variables will be summarized: 
 
Demographic variables: Age at screening (year), age group, sex, ethnicity, race, baseline 
weight (kg) with grouping (<60 kg, 60 kg), BMI (kg/m2) with grouping (<20, 20) 
 
Baseline characteristics: Age of disease onset with grouping (<18 years, 18 years), peak 
pruritus numerical rating scale (ppNRS), 
 Global Assessment (IGA) score, 
Eczema Area and Severity Index (EASI) score, SCORing Atopic Dermatitis (SCORAD) 
score, Body Surface Area (BSA) affected by AD, Dermatology Life Quality Index (DLQI) 
Descriptive statistics for these variables will be presented for all populations, by treatment group, 
and both treatment groups combined. Continuous variables will be summarized with n, mean, 
SD, and median. Categorical variables will be summarized with n and % of subjects for each 
category for the mITT, and PP populations.  
6.5 
Medical History 
Subject incidence (n and %) of medical history (and current medical condition before signing the 
informed consent) will be tabulated by the Medical Dictionary for Regulatory Activities 
(MedDRA), version 21.0) System Organ Class (SOC) and Preferred Term (PT). 
6.6 
Electrocardiogram 
A listing of electrocardiograms (ECG) overall interpretation at screening visit will be provided. 
6.7 
Pregnancy Test 
A listing of pregnancy test results will be provided. 
6.8 
Treatments 
6.8.1 
Treatment Compliance  
Summaries of treatment compliance will be based on the safety population. 
The compliance with study treatment will be calculated as follows: 


 
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Treatment Compliance = (Number of study drug injections during exposure period)/ (Number of 
planned study drug injections during exposure period) x 100%. 
The treatment compliance will be presented by the following specific ranges for each treatment 
 
In addition, an overall compliance that includes adherence to treatment administration schedule 
and any interruptions will be included in the data listing. 
6.8.2 
Prior, Concomitant, and Newly Initiated Medications  
Prior medications and concomitant medications will be extracted from the Prior/Concomitant 
Medication CRF. Medications taken prior to Study Day 1 will be considered as prior 
medications, medications taken on or after Study Day 1 will be considered as concomitant 
medications, and newly initiated medication refers to any medication with a start date 
 Study Day 1. We note that a Prior Medication may also be a Concomitant Medication if the 
start date is prior to Study Day 1 and the end date is on/after Study Day 1. Medications will be 
coded using the WHO Drug Dictionary (WHODD March 2018 release) for preferred term (PT) 
and Anatomical Therapeutic Chemical (ATC) classification.  
Medications will be tabulated separately based on the Safety population. The number (n and %) 
of subjects taking at least 1 medication and the number (%) of subjects taking each medication at 
the preferred term level will be tabulated by ATC4, and PT. Subjects taking the same PT 
medication twice will only be counted once. 
A subject data listing will be provided to include the reported medication name, the WHODD 
PT, ATC4, study day and pertinent subject information.  
6.9 
Analyses of Efficacy Endpoints 
For all efficacy variables, the analysis will be comparison of lirentelimab SC and the placebo 
treatment groups. The following null and alternative hypotheses for the primary endpoint will be 
tested for lirentelimab SC group and the placebo group: 
H0: No treatment difference between lirentelimab SC and placebo 
H1: There is a treatment difference between lirentelimab SC and placebo 
Baseline disease severity index [moderate (IGA=3) and severe (IGA=4)] and prior biologic 
experience (biologic-naïve and biologic-exposed) will be the 2 stratification factors for subject 
randomization and will be accounted for in the statistical modeling for efficacy. In addition, if it 


 
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is evident that the primary endpoint is confounded by study entry characteristics [e.g., the 
method of IGA and/or EASI score assessment by AD specialist (defined as the PI and or Sub-I 
being either an allergist, immunologist or dermatologist) as compared to non-AD specialist, 
change in percent BSA greater than 20% at the end of the Lead-in Phase (Day -14 to Day -8) 
compared to the end of the Baseline Phase (Day -7 to Day -1)], then the primary efficacy 
analysis will be conducted adjusting for the effects of the background characteristics.  
6.9.1 
Analysis of Primary Efficacy Endpoint 
The primary responder endpoint will be analyzed using the Cochran-Mantel-Haenszel test 
adjusted by baseline disease severity index [moderate (IGA=3) and severe (IGA=4)], prior 
biologic experience (biologic-naïve and biologic-exposed), and country (USA and Germany) at 
Week 14. A sample SAS code is as follows: 
 
* COMPUTES CMH P-VALUE AND NEWCOMBE COMMON RISK DIFFERENCE ; 
ods output CMH=PVAL(where=(althypothesis='Row Mean Scores Differ')) 
CommonPdiff=DIFF; 
proc freq data=ADEF ; 
 
tables DISEASE_INDEX*BIOLOGIC_EXPERIENCE*COUNTRY*TRTP*RESP / 
cmh(MF) commonriskdiff  
(cl=NEWCOMBE) ; 
run ; 
The Mantel-Fleiss (MF) criterion will be performed, and if it is not met while using the option 
CMH (MF) in SAS procedure PROC FREQ, analyses including each factor separately in CMH 
test will be conducted. Should assumption per the MF criterion not be satisfied, the comparison 
will be based on a Fisher
 across levels of the stratification factor and 
country. 
Below is an example of the SAS code for the 
: 
 
* COMPUTE 95% EXACT CONFIDENCE INTERVAL FOR %RESPONSE FOR INDIVIDUAL 
TREATMENT ; 
ods output BinomialCLs=CL ; 
proc freq data=ADEF ; 
 
table RESP / out=CNTS bin(cl=midp) ; 
 
by TRTP ; 
run; 
 
For the analysis described above, subjects who prematurely discontinue the randomized 
treatment or initiate any treatment adjustments (e.g., use of prohibited/rescue medication/rescue 
treatment for AD symptoms) will be handled as described below: 


 
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If a subject withdraws from the study, this subject will be counted as a non-responder for 
the time points after withdrawal 
 
To account for the impact of prohibited/rescue medication/rescue treatment for AD 
symptoms on the efficacy effect: if rescue medication/rescue treatment for AD symptoms is 
used (see Appendix 1: Intercurrent Events and Definitions of Prohibited Medication Use 
and Rescue Medication/Treatment for AD Symptoms for definitions of ICE and listings of 
prohibited medications and rescue medications/therapies), the subject will be specified as a 
non-responder from the time the rescue medication/rescue treatment is used 
 
If the subject has the missing value at Week 14, it will be counted as a non-responder at 
Week 14 
The primary efficacy analysis will be performed on the mITT population, as well as PP 
population as a supporting analysis. In addition, for completeness purposes, results including all 
subjects and excluding the subjects who had major protocol deviations on the basis of key 
inclusion and exclusion criteria defining the population of interest will be presented. The 
differences between these results will be noted, and the impact of such differences will be 
discussed in the clinical study report. 
6.9.2 
Analysis of Secondary Efficacy Endpoints 
The binary secondary efficacy endpoint will be analyzed using the same approaches as that are 
used for the analysis of the primary endpoint. 
Mixed Model for Repeated Measures (MMRM) analyses will be performed on continuous 
endpoints to mitigate the impact of missing data. This approach assumes missing observations 
are missing at random and borrows information from subjects in the same treatment group, 
taking into account the missingness of data through the correlation of the repeated 
measurements.  
All continuous endpoints will utilize MMRM after applying the primary censoring rule, i.e., the 
rule will censor data after permanent study drug discontinuation or after rescue therapy. This 
censoring rule is equivalent to using all the data up to discontinuation or rescue. 
The MMRM model will include fixed effects for baseline value, disease severity group, biologic-
naïve vs biologic-exposed, country, treatment, study week, the treatment-by-week interaction, 
and the baseline-by-week interaction and allow for random subject effects. Treatment and week 
will each be fitted as categorical variables. The model will assume unstructured covariance 
structure. If the model with unstructured covariance does not converge, then other covariance 


 
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structures will be considered to model the within-subject errors. The Kenward-Rogers approach 
for computing denominator degrees of freedom will be used to account appropriately for pooling 
of within-subject and between-subject variance estimates. Efficacy data on subjects who 
prematurely discontinue the randomized treatment or initiate any treatment adjustments (e.g., use 
of prohibited/rescue medication/rescue treatment for AD symptoms) will be set to missing at the 
designated time points after withdrawal or after the start of such treatment changes. The LSM 
and 95% CI for the difference between groups will be estimated using the simple contrast at each 
time point. Below is an example of the SAS code for the MMRM: 
 
proc mixed data=EASI method=reml; 
   class TRTP USUBJID AVISITN COUNTRY DISEASE_INDEX 
BIOLOGIC_EXPERIENCE; 
   model PCHG= B_EASI TRTP AVISITN COUNTRY DISEASE_INDEX 
BIOLOGIC_EXPERIENCE TRTP*AVISITN B_EASI*AVISITN / DDFM=KR; 
REPEATED AVISITN / SUBJECT=USUBJID (TRTP) TYPE=UN; 
RANDOM COUNTRY; 
LSMEANS TRTP*AVISITN / PDIFF CL; 
RUN; 
Where TRTP = planned treatment group in numeric (1 = placebo, 2 = lirentelimab SC); 
AVISITN = time point (i.e., Weeks 2, 4, 6, 8, 10, 12, and 14). 
6.10 
Analysis of Exploratory Endpoints  
6.10.1 
Change from Baseline in 
 
The endpoint will be analyzed using the same approaches as that are used for the analysis of the 
secondary efficacy continuous endpoint of percent change in EASI.  
6.10.2 
Time to Onset of Response on 
  
Time to onset of effect on 
 as measured by proportion of subjects with 
 
 of weekly average of daily 
 during the 14-week 
treatment period will be calculated for each subject as the date of having the first event - the first 
study drug dose date + 1 day. Subjects not having any event during the treatment period will 
have their time censored at the end of the treatment period. Time to onset of effect on 
 
will be analyzed using the Cox proportional hazards model including treatment, randomization 
strata, and country as factors. The hazards ratio  95% confidence interval and p-value will be 
reported. Kaplan-Meier curves will be provided. A sample of the SAS code is provided below: 
 
proc phreg data=
 
  class TRTP (ref='1') DISEASE_INDEX (ref='1')BIOLOGIC_EXPERIENCE (ref='1'); 
  model aval*cnsr(1) = DISEASE_INDEX BIOLOGIC_EXPERIENCE TRTP /     
ties=exact rl; 


 
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  strata COUNTRY; 
run; 
quit; 
Where TRTP = planned treatment group in numeric (1 = placebo, 2 = lirentelimab SC); 
DISEASE_INDEX = baseline disease severity index [1 = moderate (IGA=3) and 2 = severe 
(IGA=4)]; BIOLOGIC_EXPERIENCE = prior exposure to biologics [1 = biologic-naïve and 2 = 
biologic-exposed). 
6.10.3 
 Responder Rate 
The endpoint will be analyzed using the same approaches as used for the analysis of the primary 
endpoint. A 
 responder is a subject who had at least a 
 reduction in score between 
the visit and baseline. A 
 responder is similarly defined. 
6.10.4 
Percent and Change from Baseline in 
 
These endpoints will be analyzed using the same approaches as that are used for the analysis of 
the secondary efficacy continuous endpoint of percent change in EASI. 
The model will include fixed effects for baseline value, disease severity index, biologic-naïve vs 
biologic-exposed, country, treatment, study week, the treatment-by-week interaction, and the 
baseline by-week interaction and allow for random subject effects. Treatment and week will each 
be fitted as categorical variables. The model will assume unstructured covariance structure. If the 
model with unstructured covariance does not converge, then other covariance structures will be 
considered to model the within-subject errors. The Kenward-Rogers approach for computing 
denominator degrees of freedom will be used to account appropriately for pooling of within-
subject and between-subject variance estimates. Data on subjects who prematurely discontinue 
the randomized treatment or initiate any treatment adjustments (e.g., use of prohibited/rescue 
medication) will be set to missing at the designated time points after withdrawal or after the start 
of such treatment changes. If fewer than 4 days of data are recorded within a particular week, the 
data for that week will be considered insufficient and the data will be set to missing for that 
week. Missing data entries in the eDiary and data set to missing as illustrated above will not be 
imputed. 
6.10.5 
Change from Baseline in 
  
The endpoint will be analyzed using the same approaches as that are used for the analysis of the 
secondary efficacy continuous endpoint of percent change in EASI.  




 
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The 
 is calculated by summing the score of each question resulting in a maximum of 
 
and a minimum of  The higher the score, the more 
 ( 


 
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Table 4, Table 5).  
 




 
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6.11 
Analysis of Pharmacokinetic Endpoint 
The analysis of the PK concentration will be based on the Safety population. Lirentelimab SC 
concentrations will be listed by treatment, subject, nominal time, and actual time. Concentrations 
that are below limit of quantification (BLOQ) will be indicated in the listing.  
Plasma concentrations will be summarized at each nominal time point separately for each 
treatment. The following descriptive statistics will be presented: n, arithmetic mean, SD, 
geometric mean, % CV, median, minimum, and maximum.  
Individual plasma concentration vs. actual times will be plotted for each subject in linear and 
semi-logarithmic scales, placed on the same page. Mean plasma concentration at the scheduled 
time points will be plotted for each treatment in linear and semi-logarithmic scale, with the 
associated standard errors (for linear scale only) at each scheduled time point. 
In the plot, concentrations that are BLOQ will be assigned a value of 0 if they are collected 
predose or assigned a value of 1/2 the lower limit of quantification (LLOQ) if they are collected 
postdose.  
Analysis of PK parameters are specified separately in a PK analysis plan. 
6.12 
Safety Analyses 
6.12.1 
Adverse Events 
Safety assessments will be based mainly on the nature, frequency, relationship, and severity of 
adverse events (AE). The AE will be coded by primary System Organ Class (SOC) and Preferred 
Term (PT) according to MedDRA (version 21.0). The treatment-emergent adverse events 
(TEAE) will be summarized by the number and percentage (n and %) of subjects in each SOC 
and PT.  
reported with the same PT, the AE of the strongest relation to study drug will be included in the 
summary by relationship, and the AE of the most severe grade will be included in the summary 
by severity table. 
The following AE incidence tables will be presented.  
 
Overview of TEAE to include 
 Number (%) of subjects who reported at least 1 TEAE  


 
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 Number (%) of subjects who reported at least 1 treatment related TEAE 
 Number (%) of subjects who reported at least 1 severe TEAE 
 Number (%) of subjects who reported at least 1 serious TEAE  
 Number (%) of subjects who reported at least 1 TEAE leading to treatment 
discontinuation  
 Number (%) of subjects who reported at least 1 TEAE leading to study discontinuation  
 Number (%) of subjects who reported at least 1 TEAE of special interest (TEAESI) 
 
TEAE by PT sorted by decreasing order of subject incidence in the combined treatment 
group 
 
TEAE by SOC and PT in alphabetical order 
 
TEAE by SOC, PT, and maximum severity 
 
TEAE by SOC, PT, and strongest relationship to study drug  
 
TEAE leading to treatment discontinuation by SOC and PT, if warranted by sample size 
 
TEAE leading to study discontinuation by SOC and PT, if warranted by sample size 
 
Serious TEAE by SOC and PT, if warranted by sample size 
 
TEAESI by SOC and PT 
All AE will be listed with onset/stop day, relationship to study drug, severity, action taken, and 
outcome. Pertinent subject information including treatment group and demographics will also be 
included.  
Separate listings will be provided for TEAE leading to study discontinuation, TEAE of special 
interest, and treatment-emergent serious AE (TESAE).  
6.12.2 
Laboratory Test 
Laboratory data will be summarized by presenting summary statistics of raw data and change 
from baseline values (means, medians, standard deviations, ranges). For quantitative laboratory 
parameters, both actual values and change from baseline values will be summarized at each visit. 
Shift tables will be presented, in which, lab test results at baseline and post-baseline visit will be 
e (>ULN) normal ranges. 
Subject incidences (n and %) will be presented for the shift from baseline to the post-baseline 
visits. 


 
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Note that the analysis window will be applied for the visits. 
A complete laboratory data listing, including hematology, biochemistry, and urinalysis will be 
provided for all subjects.  
6.12.3 
Vital Signs, Height and Weight, and Other Safety Measures 
Vital signs will be summarized by presenting summary statistics of raw data and change from 
baseline values (means, medians, standard deviations, ranges) for each visit (per analysis 
window) and time point. A data listing will include vital signs from all visits.  
6.12.4 
Electrocardiogram 
I
 not clinically significant, 
and abnormal  clinically significant) will be summarized. 
6.12.5 
Physical Examination 
New or worsening symptoms in the symptom-directed physical exams will be included in the 
by -subject data listing. 
6.12.6 
Analysis of Anti-Drug Antibodies 
A data listing of anti-drug-antibodies (ADA) results will be provided for all subjects. Number 
(%) of subjects who are confirmed ADA-positive at any time after receiving study drug and 
number (%) of subjects who are confirmed ADA-positive at the end of study will be cross-
tabulated by their ADA status and titers at predose. 
7. 
Validation  
The Clinical Operations and Data Management at Allakos will work with the EDC/Data 
Management (DM) vendor to ensure that the data collected for the study is of the highest quality 
possible. The study monitor will be responsible for reviewing and verifying the accuracy of the 
data recorded on the eCRF directly from source documents at the investigative site. The DM 
vendor will be responsible for performing edit checks and reviewing all data entered into the 
electronic database to identify discrepant and/or inconsistent values and to send queries to the 
clinical sites. The Investigator will be responsible for answering queries about discrepant data 
and providing electronic signatures to confirm data integrity.  
The programming of tables, listings, and figures (TLF) based on the clinical data is outsourced. 
Allakos seeks to ensure the quality of the reports provided by the CRO in the form of TLF 
passing a rigorous validation process as follows:  


 
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Derived datasets will be independently reprogrammed by a second programmer. The 
separate datasets produced by the 2 programmers must match 100%.  
 
Tables will be independently reprogrammed by a second programmer, and the results from 
both programs must match.  
 
Figures will be checked for consistency against corresponding tables and listings or 
independently reprogrammed if there are no corresponding tables or listings.  
 
Listings will be checked for consistency against corresponding tables, figures, and derived 
datasets.  
All post hoc analysis, if accepted for inclusion in the study report, will follow the same quality 
process as stated above. The entire set of TLF will be checked for completeness and consistency 
prior to delivery to Allakos.  
8. 
References 
International Council for Harmonisation (ICH). Guideline for industry E3, structure and content 
of clinical study reports, July 1996.  
Food and Drug Administration. E9 (R1) Statistical Principles for clinical trials: addendum: 
estimands and sensitivity analysis in clinical trials. Guidance for industry, ICH, 
May 2021. 
Mehta, C. R., & Pocock, S. J. (2011). Adaptive increase in sample size when interim results are 
promising: a practical guide with examples. Statistics in medicine, 30(28), 3267-3284. 
 
 
 


 
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9. 
Appendices 
9.1 
Appendix 1: Intercurrent Events and Definitions of Prohibited Medication Use and 
Rescue Medication/Treatment for AD Symptoms 
9.2 
Appendix 2: List of Tables, Figures, and Listings 
 


 
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9.1 
Appendix 1: Intercurrent Events and Definitions of Prohibited Medication Use and 
Rescue Medication/Treatment for AD Symptoms 
 
Intercurrent events (ICE) are considered to potentially confound the efficacy outcomes of the 
study and are defined as follows: 
 
Premature discontinuation from the double-blind portion of the study for any reason  
 
Use of prohibited medications during the study 
 
Use of rescue medication/therapy for symptoms of AD 
Prohibited medications are defined as therapies that should not be taken during the course of the 
study either because of a potential impact on the assessment of efficacy and/or subject safety. 
Rescue medications/treatments are defined as any therapy or treatment taken during the course of 
the study for the specific purpose of alleviating AD symptoms that may have an impact on the 
assessment of efficacy and includes: (1) topical medications (including TCS, TCI and 
crisaborole), (2) systemic medications (including systemic corticosteroids, immunosuppressant, 
and biologics), and (3) treatments known to impact AD. 
The following provides the details of the prohibited medications/therapies for this study: 
1) 
Prohibited medications where route of administration includes topical/transdermal 
 
Topical Corticosteroids (TCS): ATC code D07 
High Potency TCS: ATC codes D07AC or D07AD 
Low or moderate potency TCS: ATC code D07, excluding D07AC or D07AD 
Topical calcineurin inhibitors (TCI): where Preferred Term includes tacrolimus, 
pimecrolimus  
Coal tar: ATC code D05AA 
Phosphodiesterase-4 Inhibitors (PDEi): ATC code L04AA32 where Preferred Term 
includes Crisaborole: ATC code D11AH, roflumilast (no topical ATC code) or apremilast 
gel 
 
2) 
Prohibited systemic medications (including systemic corticosteroids, immunosuppressants, 
immunomodulators, and biologics) 
 
Systemic corticosteroids: ATC code is H02 
Immunosuppressants or immunomodulators: ATC code is L04  
Mycophenolate: ATC code is L04AA06 
Methotrexate: ATC code is L04AX 
Interferons: gamma: ATC code is L03AB where Preferred Terms include interferon 
gamma, interferonalfa-2b 


 
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Leukotriene inhibitors: ATC code is R03DC where Preferred Term includes Ibudilast, 
Montelukast, Pranlukast, and Zafirlukast 
Oral calcineurin inhibitors: ATC code is L04AD where Preferred Term includes 
Ciclosporin, Cyclosporin, Tacforius, Tacrolimus, Voclosporin 
IV immunoglobulins: ATC code is J06B 
Doxepin: ATC code is N06AA 
Janus Kinase inhibitors (JAKi): ATC code is L01EJ where Preferred Term includes 
Delgocitinib, Fedratinib, Pacritinib, Ruxolitinib and ATC code is D11AH with Preferred 
Term Abrocitinib 
Phosphodiesterase-4 Inhibitors (PDEi): ATC code L04AA32 where Preferred Term 
includes apremilast (oral) 
TNF inhibitors: ATC code is L04AB where Preferred Term includes Adalimumab, 
Afelimomab, Certolizumab, Etanercept, Golimumab, Infliximab, Opinercept, 
Ozoralizumab 
 
Note 1: The use of a short course of systemic corticosteroids for a medical condition 
other than atopic dermatitis, in the event of medical necessity when no alternative non-
steroid treatment is available, will be allowed provided that the use is limited to less than 
5 days and the therapy is not taken within 28 days of the Day 99 visit. 
 
Note 2: Leukotriene inhibitors: ATC code is R03DC where Preferred Term includes 
Ibudilast, Montelukast, Pranlukast, and Zafirlukast are permitted during the study 
provided that doses remain stable throughout the study unless change is required for an 
unforeseen medical necessity. Initiation of any new leukotriene inhibitor is prohibited. 
 
 
Biologics:  
Agents For Dermatitis, Excluding Corticosteroids: ATC code is D11A where preferred 
terms include Dupilumab, Tralokinumab 
CD20 inhibitors: ATC code is L01F where preferred terms include Obinutuzumab, 
Ofatumumab  
Selective Immunosuppressants: ATC code is L04AA where preferred terms include 
Abatacept, Abetimus, Alemtuzumab, Anifrolumab, Apremilast, Baricitinib, Begelomab, 
Belatacept, Belimumab, Belumosudil, Deucravacitinib, Eculizumab, Efalizumab, 
Emapalumab, Filgotinib, Fingolimod, Inebilizumab, Itacitinib, Natalizumab, 
Ocrelizumab, Ofatumumab, Ozanimod, Peficitinib, Pegcetacoplan, Ponesimod, 
Ravulizumab, Sutimlimab, Teprotumumab, Teriflunomide, Tofacitinib, Upadacitinib, 
Vedolizumab 
Interleukin Inhibitors: ATC code is L04AC where preferred terms include Anakinra, 
Basiliximab, Bimekizumab, Briakinumab, Brodalumab, Canakinumab, Daclizumab, 
Guselkumab, Ixekizumab, Netakimab, Olokizumab, Rilonacept, Risankizumab, 
Sarilumab, Satralizumab, Secukinumab, Siltuximab, Sirukumab, Spesolimab, 
Tildrakizumab, Tocilizumab, Ustekinumab 
Unspecified Immunosuppressants: No ATC code with Preferred Term including 
Barzolvolimab, Fezakinumab, Fletikumab, Gevokizumab, Gusacitinib, Ladarixin, 


 
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Lebrikizumab, Ligelizumab, Mirikizumab, Nemolizumab, Olamkicept, Tabalumab, 
Tregalizumab 
Other Systemic Drugs for Airway Disease: ATC code R03D with Preferred Term 
including Benralizumab, Mepolizumab, Omalizumab, Reslizumab, Roflumilast, 
Tezepelumab and ATC code is R03DX with Preferred Term including Rituximab 
 
3) 
The use of prescription emollients or emollients containing additives such as ceramide, 
hyaluronic acid, urea, or filaggrin are not allowed during the course of the study except as 
rescue therapy. 
4) 
Treatments for Atopic Dermatitis:  
The use of ultraviolet A or B (UVA or UVB), psoralen + UVA (PUVA), other 
phototherapy, or tanning beds is also not permitted during the study. The use of a tanning 
bed will not be considered rescue therapy. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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9.2 
Appendix 2: List of Tables, Figures, and Listings 
Tables 
Table 14.1.1a 
Subject Disposition and Reason for Discontinuation (All Screened Subjects) 
Table 14.1.1b  
Subject Disposition and Reason for Discontinuation 
(Safety/mITT Population) 
Table 14.1.1c 
Subject Disposition and Reason for Discontinuation 
(Per Protocol Population) 
Table 14.1.2 
Major Protocol Deviations and Violations During the Study: Subject Count 
(All Randomized Subjects) 
Table 14.1.3 
Analysis Population: Subject Count (All Randomized Subjects) 
Table 14.1.4 
Per Protocol Population Exclusion (All Randomized Subjects) 
Table 14.1.5a 
Demographics and Baseline Characteristics (Safety/mITT Population) 
Table 14.1.5b 
Demographics and Baseline Characteristics (Per Protocol Population) 
Table 14.1.6 
Medical History by System Organ Class and Preferred Term: Subject 
Incidence (Safety/mITT Population) 
Table 14.1.7 
Study Drug Compliance (Safety Population) 
Table 14.1.8.1 
Prior Medications by Anatomic Therapeutic Chemical Classification and 
Preferred Term: Subject Incidence (Safety Population) 
Table 14.1.8.2  
Concomitant Medications by Anatomic Therapeutic Chemical 
Classification and Preferred Term: Subject Incidence (Safety Population) 
Table 14.1.9 
Severity of Concomitant Asthma and Atopic Dermatitis at Baseline 
(MITT Population) 
Table 14.1.10 
12-Lead ECG Evaluation at Baseline (Safety Population) 
Table 14.1.11 
Baseline Eosinophil and Mast Cell Counts (mITT Population) 
Table 14.1.12 
Baseline 
 (mITT Population) 
Table 14.1.13 
Baseline Vital Signs (mITT Population) 
Table 14.1.14 
Subject Incidence of Intercurrent Events (mITT Population) 


 
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Table 14.2.1.1a 
EASI-75 Responder at Week 14  Primary Analysis (mITT Population) 
Table 14.2.1.1b 
EASI-75 Responder at Week 14  Supportive Analysis of Primary Endpoint 
(PP Population) 
Table 14.2.1.1c 
EASI-75 Responder at Week 14  Sensitivity Analysis of Primary Endpoint 
(All Subjects All Data) 
Table 14.2.1.2.1 
EASI-75 Responder at Week 14 by Gender (mITT Population) 
Table 14.2.1.2.2 
EASI-75 Responder at Week 14 by Age Group (mITT Population) 
Table 14.2.1.2.3 
EASI-75 Responder at Week 14 by Race (mITT Population) 
Table 14.2.1.2.4 
EASI-75 Responder at Week 14 by Ethnicity (mITT Population) 
Table 14.2.1.2.6 
EASI-75 Responder at Week 14 by Duration of AD (mITT Population) 
Table 14.2.1.2.7 
EASI-75 Responder at Week 14 by Age of Disease Onset (mITT 
Population) 
Table 14.2.1.2.8 
EASI-75 Responder at Week 14 by Family History of Atopic Disease 
(mITT Population) 
Table 14.2.1.2.9 
EASI-75 Responder at Week 14 by Disease Severity Index (mITT 
Population) 
Table 14.2.1.2.10 
EASI-75 Responder at Week 14 by EASI Severity Index (mITT Population) 
Table 14.2.1.2.11 
EASI-75 Responder at Week 14 by Peak Pruritus Numeric Rating Scale 
Group (mITT Population) 
Table 14.2.1.2.12 
EASI-75 Responder at Week 14 by Body Surface Area Group mITT 
Population) 
Table 14.2.1.2.13 
EASI-75 Responder at Week 14 by Prior Biologic Experience 
(mITT Population) 
Table 14.2.2.1a 
Percent Change from Baseline in EASI (mITT Population) 
Table 14.2.2.1b 
Percent Change from Baseline in EASI (PP Population) 
Table 14.2.3a 
Percentage of Subjects with IGA of 0 or 1 and a 2-Point Improvement at 
Week 14 Compared with Baseline (mITT Population) 


 
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Table 14.2.3b 
Percentage of Subjects with IGA of 0 or 1 and a 2-Point Improvement at 
Week 14 Compared with Baseline (PP Population) 
Table 14.2.4 
Change from Baseline in 
 (mITT Population) 
Table 14.2.5 
Time to Onset of Effect on 
 (mITT 
Population) 
Table 14.2.6 
Change from Baseline in 
 (mITT Population) 
Table 14.2.7 
Change from Baseline in 
 
(mITT Population) 
Table 14.2.8 
Change from Baseline in 
 (mITT 
Population) 
Table 14.2.9 
Change from Baseline in 
 (mITT Population) 
Table 14.2.10 
 Responder (mITT Population) 
Table 14.2.11 
 Responder (mITT Population) 
Table 14.2.12 
Change from Baseline in Percent 
 (mITT Population) 
Table 14.2.13 
Change from Baseline in 
 (mITT 
Population) 
Table 14.2.14 
Total Serum IgE Concentration (mITT Population) 
Table 14.2.15 
Subject Incidence of Positive Anti-Drug (AK002) Antibody (ADA) Test 
(Safety Population) 
Table 14.3.1.1 
Overview of Treatment-Emergent Adverse Events (Safety Population) 
Table 14.3.1.2 
Treatment-Emergent Adverse Events by Preferred Term: Subject Incidence 
(Safety Population) 
Table 14.3.1.3 
Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term: Subject Incidence (Safety Population) 
Table 14.3.1.4 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Maximum Severity: Subject Incidence (Safety Population) 


 
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Table 14.3.1.5 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Relationship to Study Drug: Subject Incidence 
(Safety Population) 
Table 14.3.1.6 
Treatment-Emergent Adverse Events Leading to Study Drug 
Discontinuation by System Organ Class and Preferred Term: Subject 
Incidence (Safety Population) 
Table 14.3.1.7 
Treatment-Emergent Serious Adverse Events by System Organ Class and 
Preferred Term: Subject Incidence (Safety Population) 
Table 14.3.1.8 
Treatment-Emergent Adverse Events of Special Interest by System Organ 
Class and Preferred Term: Subject Incidence (Safety Population) 
Table 14.3.2.1 
Hematology: Change from Baseline by Visit (Safety Population) 
Table 14.3.2.2 
Blood Chemistry: Change from Baseline by Visit (Safety Population) 
Table 14.3.2.3 
Hematology: Shift from Baseline Classification by Visit (Safety Population) 
Table 14.3.2.4 
Blood Chemistry: Shift from Baseline Classification by Visit 
(Safety Population) 
Table 14.3.2.5 
Urinalysis: Change from Baseline by Visit (Safety Population) 
Table 14.3.3 
Summary of Vital Signs by Visit (Safety Population) 
 
Figures 
Figure 1 
EASI-75 Responder Over Time (mITT Population) 
Figure 2 
Percent Change from Baseline in EASI Over Time (mITT Population) 
Figure 3 
Percentage of Subjects with IGA of 0 or 1 and a 2-Point Improvement Over 
Time Compared with Baseline (mITT Population) 
 
 


 
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Listings 
Listing 16.1.7 
Subject Randomization Schedule (Randomized Population) 
Listing 16.2.1.1 
Subjects Disposition and Reason for Disposition (Randomized Population) 
Listing 16.2.1.2 
Subjects Who had Major Protocol Deviations (Randomized Population) 
Listing 16.2.1.3 
Subjects Inclusion and the Reason for Exclusion from Analysis Populations 
(Randomized Population) 
Listing 16.2.1.4.1 
Demographic and Baseline Characteristics (Safety Population) 
Listing 16.2.1.4.2 
Demographic and Baseline Characteristics  History of Disease 
(Safety Population) 
Listing 16.2.1.5 
Medical History (Safety Population) 
Listing 16.2.1.6 
Atopic Conditions Questionnaire (Safety Population) 
Listing 16.2.1.7.1  
Prior Medications (Safety Population) 
Listing 16.2.1.7.2 
Concomitant Medications (Safety Population) 
Listing 16.2.1.8 
Intercurrent Events (Safety Population) 
Listing 16.2.3.1.1 
All Adverse Events (Safety Population) 
Listing 16.2.3.1.2 
Serious Adverse Events (Safety Population) 
Listing 16.2.3.1.3 
Adverse Events with Outcome of Death (Safety Population) 
Listing 16.2.3.1.4 
Adverse Events Leading to Study Drug Discontinuation (Safety Population) 
Listing 16.2.3.1.5 
Adverse Events of Special Interest (Safety Population) 
Listing 16.2.3.2.1 
Clinical Laboratory Tests-Hematology (Safety Population) 
Listing 16.2.3.2.2 
Clinical Laboratory Tests  Blood Chemistry (Safety Population) 
Listing 16.2.3.2.3 
Clinical Laboratory Tests  Urinalysis (Safety Population) 
Listing 16.2.3.2.4 
Clinical Laboratory Tests  Diagnostic Immunology/Molecular Biology 
(Safety Population) 
Listing 16.2.3.2.5 
Clinical Laboratory Tests  Endocrinology (Safety Population) 


 
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Listing 16.2.3.2.6 
Clinical Laboratory Tests  Parasitology (Safety Population) 
Listing 16.2.3.3.1 
Substance Use  Alcohol Consumption at Screening (Safety Population) 
Listing 16.2.3.3.2 
Urine Pregnancy Test (Safety Population) 
Listing 16.2.3.4.1 
Study Drug Administration (Safety Population) 
Listing 16.2.3.4.2 
Study Drug Accountability (Safety Population) 
Listing 16.2.3.5 
Vital Signs (Safety Population) 
Listing 16.2.3.6 
Subject Body Size (Safety Population) 
Listing 16.2.3.7.1 
12-Lead ECG Intervals at Baseline (Safety Population) 
Listing 16.2.3.7.2 
12-Lead ECG Overall Interpretation (Safety Population) 
Listing 16.2.3.8 
Physical Examination (Safety Population) 
Listing 16.2.3.9 
Antidrug (AK002) Antibody (ADA) Test (Safety Population) 
Listing 16.2.3.11 
Serum Concentrations of IgE (Safety Population)