Clinical trial NCT04856891
Conditions: Eosinophilic Duodenitis Eosinophilic Gastroenteritis
Keywords: Eosinophil Eosinophilic Eosinophilic gastrointestinal disorders EGID EoD
Sponsor: Allakos Inc.
Start date: 2021-05-20; Completion date: 2023-01-09
Enrollment: 94 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult patients with active eosinophilic duodenitis. Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.

Detailed description:

Arms: arm 1: Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg. arm 2: Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.
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 documents:
Prot_000.pdf: 
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Efficacy and Safety of AK002 in Patients with Moderately to Severely 
Active Eosinophilic Duodenitis who have an Inadequate Response with, Lost 
Response to, or were Intolerant to Standard Therapies 
NCT Number: NCT04856891 
IRB Approval Date: 13 Jul 2022
Document Date: 16 Jun 2022


 
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Pa ge 1 of 1 4 0  
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A P h ase 3, M ultice nter, R a n d o mize d, D o u ble -Bli n d, Pl ace b o -C o ntr olle d St u d y  
t o E v al u ate t he Effic ac y a n d S afet y of A K 0 0 2 i n P atie nts wit h M o der atel y t o 
Se verel y Acti ve E osi n o p hilic D u o de nitis w h o h a ve a n I n a de q u ate Res p o nse wit h, 
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Pr ot oc ol N u m ber  
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I n vesti gati o nal Pr o d uct 
A K 0 0 2 (lire nteli ma b) 
St u d y P hase  
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Alla k os I nc . 
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T his c o nfi de ntial i nf or mati o n a b o ut a n i n vesti gati o nal pr o d uct is pr o vi de d f or t he e xcl usi ve use 
of I n vesti gat ors of t his pr o d uct a n d is s u bject t o recall at a n y ti me. T he i nf or mati o n i n t his 
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S u bject t o t he f or e g oi n g, t his i nf or mati o n ma y be discl ose d o nl y t o t h ose pers o ns i n v ol ve d i n t he 
st u d y w h o ha ve a nee d t o k n o w, wit h t he o bli gati o n n ot t o f urt her disse mi nate t his i nf or mati o n.  
1 6 - J u n - 2 0 2 2  |  0 9 : 3 8  P D T
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Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 2 of 140 
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Investigator Protocol Agreement 
I have read the protocol specified below. In my formal capacity as Principal Investigator, my 
duties include ensuring the safety of the study patients enrolled under my supervision and 
providing Allakos Inc. with complete and timely information, as outlined in the protocol. It is 
understood that all information pertaining to the study will be held strictly confidential and that 
this confidentiality requirement applies to all study staff at this site. Furthermore, on behalf of 
the study staff and myself, I agree to maintain the procedures required to carry out the study in 
accordance with accepted Good Clinical Practice (GCP) principles and to abide by the terms of 
this protocol. 
Protocol Number: 
AK002-021 
IND: 
135158 
NCT ID: 
04856891 
Protocol Title: 
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of AK002 in Patients with 
Moderately to Severely Active Eosinophilic Duodenitis Who Have an 
Inadequate Response with, Lost Response to, or Were Intolerant to 
Standard Therapies 
Original Protocol: 
06 January 2021 
Amendment 1:  
07 July 2021 
Amendment 2:  
16 June 2022 
 
 
 
Investigator Printed Name: _____________________________________________ 
 
 
 
Investigator Signature: 
_____________________________________________ 
 
 
 
Date: _________________________________ 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 3 of 140 
Confidential 
 
Table of Contents 
Clinical Research Protocol AK002-021 .................................................................................... 1 
Investigator Protocol Agreement .............................................................................................. 2 
Table of Contents ...................................................................................................................... 3 
List of Figures ................................................................................................................... 10 
List of Tables .................................................................................................................... 10 
List of Abbreviations ........................................................................................................ 11 
1. 
Protocol Synopsis ............................................................................................................ 15 
2. 
Background ..................................................................................................................... 29 
2.1 
Siglec-8 and AK002 .............................................................................................. 29 
2.2 
Overview of Nonclinical Studies ........................................................................... 29 
2.3 
Overview of Clinical Studies ................................................................................. 30 
2.4 
Eosinophilic Gastrointestinal Disorders ................................................................. 34 
3. 
Rationale for Study and Dose Selection ......................................................................... 35 
4. 
Study Objectives.............................................................................................................. 36 
4.1 
Primary Objective.................................................................................................. 36 
4.2 
Secondary Objectives ............................................................................................ 37 
4.3 
Exploratory Objectives .......................................................................................... 37 
4.4 
Safety Objectives ................................................................................................... 37 
4.5 
Target of Estimation .............................................................................................. 37 
4.5.1 
Population Targeted by the Scientific Question ........................................ 38 
4.5.2 
Variables of Interest (or Endpoint) Required to Address the Scientific 
Question .................................................................................................. 38 
4.5.3 
Treatment ................................................................................................ 38 
4.5.4 
Intercurrent Events .................................................................................. 38 
4.5.5 
Strategy for Handling Intercurrent Events ................................................ 39 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
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5. 
Study Design .................................................................................................................... 39 
5.1 
Study Overview ..................................................................................................... 39 
5.2 
Schedule of Events ................................................................................................ 41 
6. 
Criteria for Evaluation ................................................................................................... 47 
6.1 
Safety Endpoints ................................................................................................... 47 
6.2 
Pharmacokinetic Endpoints ................................................................................... 47 
6.2.1 
Primary Efficacy Endpoints ..................................................................... 47 
6.2.2 
Secondary Efficacy Endpoints ................................................................. 48 
6.2.3 
Exploratory Efficacy Endpoints ............................................................... 48 
7. 
Patient Selection .............................................................................................................. 49 
7.1 
Number of Patients ................................................................................................ 49 
7.2 
Number of Sites ..................................................................................................... 49 
7.3 
Study Population ................................................................................................... 49 
7.4 
Inclusion Criteria ................................................................................................... 49 
7.5 
Exclusion Criteria .................................................................................................. 50 
7.6 
Safety Evaluations ................................................................................................. 52 
8. 
Prior and Concurrent Medications ................................................................................ 52 
8.1 
Prohibited Medications .......................................................................................... 53 
8.2 
Restricted Medications .......................................................................................... 54 
8.3 
Allowed Medications ............................................................................................. 54 
9. 
Study Treatment ............................................................................................................. 55 
9.1 
Formulation of Test Product and Placebo............................................................... 55 
9.2 
Study Drug Packaging and Labeling ...................................................................... 56 
9.3 
Supply of Study Drug to the Investigational Site .................................................... 56 
9.4 
Study Drug Dosage and Dosage Regimen .............................................................. 56 
9.5 
Preparation of Study Drug ..................................................................................... 56 


 
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9. 6  
St u d y Dr u g A d mi nistr ati o n  .................................................................................... 5 7 
9. 7  
St u d y Dr u g St or a ge  ............................................................................................... 5 8 
9. 8  
St u d y Dr u g Acc o u nta bilit y  .................................................................................... 5 8 
1 0.  P atie nt N u m beri n g, St r atific ati o n, R a n d o miz ati o n, a n d Bli n di n g  ................................ 5 8 
1 0. 1  
Patie nt N u m beri n g  ................................................................................................. 5 8 
1 0. 2  
Str atificati o n a n d Ra n d o mizati o n  ........................................................................... 5 9 
1 0. 3  
Bli n di n g ................................................................................................................ 6 0 
1 0. 4  
Br ea ki n g t he Bli n d  ................................................................................................. 6 1 
1 1.  St u d y P r oce d ures a n d G ui deli nes  ................................................................................... 6 1 
1 1. 1  
Dietar y a n d Lif est yle Restricti o ns  .......................................................................... 6 2 
1 1. 2  
P har mac o d y na mic/ Efficac y -Relate d Pr oce d ures  .................................................... 6 2 
1 1. 2. 1  
E G/ E o D P R O Q uesti o n naire  .................................................................... 6 2 
1 1. 2. 2  
 ...................................................... 6 3 
1 1. 2. 3  
 
1 1. 2. 4  
E G D a n d C ol o n osc o p y wit h Bi o ps y  ......................................................... 6 3 
1 1. 2. 5  
C o m plete Bl o o d C o u nt wit h Differe ntial  .................................................. 6 5 
1 1. 2. 6  
Baseli ne Diet Assess me nt a n d C o m plia nce  .............................................. 6 5 
1 1. 2. 7  
Pr e vi o us Tr eat me nts a n d Pr oce d ure Re vie w ............................................. 6 5 
1 1. 3  
Saf et y -Relate d Pr oce d ur es  ..................................................................................... 6 6 
1 1. 3. 1  
C o nc o mita nt Me dicati o ns  ........................................................................ 6 6 
1 1. 3. 2  
C o m plete P h ysical E xa mi nati o n  .............................................................. 6 6 
1 1. 3. 3  
B o d y Wei g ht a n d Hei g ht  ......................................................................... 6 6 
1 1. 3. 4  
St o ol Sa m ple f or O va a n d Parasite  ........................................................... 6 7 
1 1. 3. 5  
S y m pt o m- Dir ecte d P h ysical E xa mi nati o n  ................................................ 6 7 
1 1. 3. 6  
Electr ocar di o gr a m  ................................................................................... 6 7 
1 1. 3. 7  
Vital Si g ns  ............................................................................................... 6 7 
C CI
C CI


 
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Amendment 2 
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11.4 
Clinical Laboratory Measurements ........................................................................ 68 
11.5 
Blood Chemistry Profile ........................................................................................ 69 
11.5.1 
Pregnancy Test and Follicle-Stimulating Hormone .................................. 69 
11.5.2 
Urinalysis ................................................................................................ 69 
11.5.3 
Serology .................................................................................................. 70 
11.5.4 
Anti-AK002 Antibodies ........................................................................... 70 
11.5.5 
Blood for Pharmacokinetics and Storage .................................................. 70 
11.5.6 
Blood for Histamine and Tryptase ........................................................... 70 
11.5.7 
Blood for IgE ........................................................................................... 70 
11.5.8 
Blood for Strongyloides stercoralis .......................................................... 71 
11.5.9 
COVID-19 Testing .................................................................................. 71 
11.6 
Effective Methods of Contraception for Allakos Studies ........................................ 71 
12. Evaluations and Procedures by Visit.............................................................................. 72 
12.1 
Screening Period ................................................................................................... 72 
12.2 
Prior to Day 1 ........................................................................................................ 73 
12.3 
Day 1 – Randomization/Infusion 1 ........................................................................ 74 
12.4 
Day 7 (not a Clinic Visit) ....................................................................................... 75 
12.5 
Day 8 (±2) ............................................................................................................. 75 
12.6 
Day 15 (±2) ........................................................................................................... 75 
12.7 
Day 28 (not a Clinic Visit) ..................................................................................... 76 
12.8 
Day 29 (±3) –Infusion 2 ........................................................................................ 76 
12.9 
Day 57 (±3) – Infusion 3........................................................................................ 77 
12.10 Day 85 (±3) – Infusion 4........................................................................................ 78 
12.11 Day 113 (±3) – Infusion 5 ...................................................................................... 79 
12.12 Day 141 (±3) – Infusion 6 ...................................................................................... 80 
12.13 Day 169 (±3) or 28 (±3) Days after Last Dose of Study Drug if ET – 
Follow-up EGD and Colonoscopy ......................................................................... 81 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 7 of 140 
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12.14 Day 176 (±3) or 35 (±3) Days after Last Dose of Study Drug if ET – 
Follow-up Visit 1 .................................................................................................. 82 
12.15 Day 197 (±3) or 56 (±3) Days after Last Dose of Study Drug if ET – 
Follow-up Visit 2 .................................................................................................. 83 
12.16 Day 225 (±3) or 84 (±3) Days after Last Dose of Study Drug if ET ....................... 83 
13. Adverse Event Reporting and Documentation .............................................................. 84 
13.1 
Adverse Events ...................................................................................................... 84 
13.2 
Serious Adverse Events ......................................................................................... 85 
13.3 
Adverse Events of Special Interest ......................................................................... 86 
13.4 
Infusion-Related Reactions .................................................................................... 86 
13.5 
Anaphylaxis .......................................................................................................... 87 
13.6 
Evaluating Adverse Events and Serious Adverse Events ........................................ 88 
13.6.1 
Establishing Diagnosis ............................................................................. 88 
13.6.2 
Assessment of Intensity ........................................................................... 88 
13.6.3 
Assessment of Causality to Study Drug ................................................... 88 
13.6.4 
Assessment of Causality to Study Procedure ............................................ 89 
13.6.5 
Action Taken ........................................................................................... 90 
13.6.6 
Assessment of Outcome ........................................................................... 90 
13.7 
Adverse Event Reporting Procedures ..................................................................... 90 
13.7.1 
All Adverse Events .................................................................................. 90 
13.7.2 
Serious Adverse Event Reporting ............................................................ 90 
13.7.3 
Pregnancy Reporting ............................................................................... 92 
13.7.4 
AESI Reporting ....................................................................................... 92 
13.8 
Medical Monitoring ............................................................................................... 93 
13.9 
Independent Data Monitoring Committee .............................................................. 93 
13.10 Study Withdrawal Criteria ..................................................................................... 93 
13.11 Study Stopping Rules ............................................................................................ 94 


 
Protocol AK002-021 
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14. Discontinuation and Replacement of Patients ............................................................... 94 
14.1 
Definition of Study Completion ............................................................................. 94 
14.2 
Early Discontinuation of Study Drug ..................................................................... 94 
15. Statistical Methods and General Considerations ........................................................... 95 
15.1 
Sample Size ........................................................................................................... 95 
15.2 
Analysis Populations ............................................................................................. 96 
15.3 
Patient Disposition ................................................................................................ 96 
15.4 
Demographic and Baseline Characteristics ............................................................ 96 
15.5 
Study Drug Exposure............................................................................................. 97 
15.6 
Efficacy Analysis .................................................................................................. 97 
15.6.1 
Primary Efficacy Endpoint Analysis ........................................................ 97 
15.6.2 
Secondary Efficacy Endpoint Analysis .................................................... 98 
15.6.3 
Exploratory Analysis ............................................................................... 99 
15.7 
Safety Analysis .................................................................................................... 100 
15.7.1 
Treatment Emergent Adverse Events ..................................................... 100 
15.7.2 
Anti-Drug Antibodies ............................................................................ 101 
15.7.3 
Clinical Laboratory Assessments ........................................................... 101 
15.7.4 
Vital Signs ............................................................................................. 101 
15.7.5 
ECG ...................................................................................................... 101 
15.7.6 
Physical Exam ....................................................................................... 101 
15.7.7 
Concomitant Medications ...................................................................... 101 
15.8 
Patient Confidentiality ......................................................................................... 101 
16. Data Collection, Retention, and Monitoring ................................................................ 102 
16.1 
Data Collection Instruments ................................................................................ 102 
16.2 
Data Management Procedures.............................................................................. 102 
16.3 
Data Quality Control and Reporting..................................................................... 102 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
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1 6. 4  
Data base L oc k/ Discl os ur e of Ra n d o mizati o n C o d e .............................................. 1 0 2 
1 6. 5  
Ar c hi vi n g of Data  ................................................................................................ 1 0 3 
1 6. 6  
A vaila bilit y a n d Rete nti o n of I n vesti gati o nal Rec or ds .......................................... 1 0 3 
1 6. 7  
M o nit ori n g .......................................................................................................... 1 0 4 
1 7.  A d mi nist r ati ve, Et hic al, a n d Re g ul at or y C o nsi der ati o ns  ............................................ 1 0 4 
1 7. 1  
Pr ot oc ol A me n d me nts  ......................................................................................... 1 0 4 
1 7. 2  
I n de pe n de nt Et hics C o m mittees/I nstit uti o nal Re vie w B oar ds............................... 1 0 4 
1 7. 3  
I nf or me d C o nse nt F or m ....................................................................................... 1 0 5 
1 7. 4  
P u blicati o ns ......................................................................................................... 1 0 6 
1 7. 5  
Cli ni cal Trial Re gistr ati o n  ................................................................................... 1 0 6 
1 7. 6  
Pa y me nt t o Patie nts  ............................................................................................. 1 0 6 
1 7. 7  
I n vesti gat or Res p o nsi bilities ................................................................................ 1 0 6 
1 8.  Ref ere nces  ..................................................................................................................... 1 0 8 
1 9.  A p pe n dices  .................................................................................................................... 1 1 0 
1 9. 1  
A p pe n di x 1: P R O Q uesti o n naire  .......................................................................... 1 1 1 
1 9. 2  
A p pe n di x 2: 
 .............................................. 1 1 4 
1 9. 3  
A p pe n di x 3: Baseli ne Diet Assess me nt  ................................................................ 1 2 0 
1 9. 4  
A p pe n di x 4: C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts ( versi o n 5. 0)  .... 1 2 1 
1 9. 5  
A p pe n di x 5: E G D a n d C ol o n osc o p y Hist ol o g y  .................................................... 1 2 2 
1 9. 6  
A p pe n di x 6: Sa m ps o n’s Criteria of A na p h yla xis  .................................................. 1 2 5 
1 9. 7  
A p pe n di x 7: e P R O T eac hi n g T o ol f or St u d y A K 0 0 2 - 0 2 1 .................................... 1 2 6 
1 9. 8  
A p pe n di x 8: 
 
1 9. 9  
A p pe n di x 9: 
 
1 9. 1 0  A p pe n di x 1 0: A d diti o nal Q uesti o ns f or D ys p ha gia a n d C o nsti pati o n  ................... 1 3 2 
1 9. 1 1  A p pe n di x 1 1: Pr e vi o us Treat me nts a n d Pr oce d ure Re vie w  .................................. 1 3 3 
1 9. 1 2  A p pe n di x 1 2: He patitis B a n d He patitis C Ser ol o gic T esti n g Details  ................... 1 3 4 
C CI
C CI
C CI


 
Protocol AK002-021 
Amendment 2 
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19.12.1 Hepatitis B Testing Details .................................................................... 134 
19.12.2 Hepatitis C Testing Details .................................................................... 134 
19.13 Appendix 13: Open-Label Extension Period – Optional ....................................... 135 
19.13.1 Summary of the Open-Label Extended Dosing Period ........................... 135 
19.13.2 OLE Objective ....................................................................................... 136 
19.13.3 OLE Eligibility Criteria ......................................................................... 136 
19.13.3.1 OLE Inclusion Criteria .......................................................... 136 
19.13.3.2 OLE Exclusion Criteria ......................................................... 136 
19.13.4 OLE Treatment ...................................................................................... 136 
19.13.5 OLE Procedures and Guidelines ............................................................ 137 
 
List of Figures 
Figure 1 
Effects Observed in Subjects at Clinical Sites that Participated in Both  
AK002-003 and AK002-016 Studies ..................................................................... 33 
 
List of Tables 
Table 1 
Study AK002-016 in Subjects with Moderate-to-Severe EG/EoD: 
Co-Primary Endpoints of Histology and Symptoms ............................................... 33 
Table 2 
Study AK002-021 Schedule of Assessments: Double-Blind Period........................ 42 
Table 3 
Adverse Event Severity per CTCAE ...................................................................... 88 
Table 4 
Adverse Event Relationship to Study Drug ............................................................ 89 
Table 5 
Adverse Event Relationship to Study Procedure .................................................... 89 
Table 6 
Hepatitis B Testing .............................................................................................. 134 
Table 7 
Hepatitis C Testing .............................................................................................. 134 
Table 8 
Study AK002-021 Schedule of Assessments: Open-Label Extension Period ........ 138 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 11 of 140 
Confidential 
List of Abbreviations 
AC 
Allergic conjunctivitis 
ADA 
Anti-drug-antibody 
ADCC 
Antibody-dependent cellular cytotoxicity 
ADL 
Activities of daily living 
AE 
Adverse event(s) 
AESI 
Adverse event(s) of special interest 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
anti-HBc 
hepatitis B core antibody 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical Classification System 
BMI 
Body mass index  
CBC 
Complete blood count 
CFR 
Code of Federal Regulation 
CI 
Confidence interval(s) 
cm 
Centimeter 
CMH 
Cochran-Mantel-Haenszel (test) 
COVID-19 
Coronavirus disease 2019 
CS 
Clinically significant 
CTCAE 
Common Terminology Criteria for Adverse Events  
CU 
Chronic urticaria 
eCDF 
Empirical cumulative distribution function 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture system 
EG 
Eosinophilic gastritis 
EGD 
Esophago-gastro-duodenoscopy 
EGE 
Eosinophilic gastroenteritis  
EGID 
Eosinophilic gastrointestinal disorders 
EGPA 
Eosinophilic granulomatosis with polyangiitis 
ELISA 
Enzyme-linked immunosorbent assay 
EoD 
Eosinophilic duodenitis (formerly referred to as eosinophilic gastroenteritis) 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 12 of 140 
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EoE 
Eosinophilic esophagitis 
ET 
Early Termination 
EU 
European Union 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GERD 
Gastroesophageal reflux disease 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice  
H. pylori 
Helicobacter pylori  
HBsAG 
Hepatis B surface antigen 
hCG 
Human Chorionic Gonadotropin 
HEENT 
Head, eyes, ears, nose, and throat 
HES 
Hypereosinophilic syndrome 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
hpf 
High-power field 
IBD 
Inflammatory bowel disease 
IBS 
Irritable bowel syndrome 
ICE 
Intercurrent event  
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
iDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IgE 
Immunoglobulin E 
IgG1 
Immunoglobulin G1 
IND 
Investigational New Drug (application) 
IP 
Investigational product 
IRB 
Institutional Review Board 
IRR 
Infusion-Related Reaction 
IRT 
Interactive Response Technology 
ISM 
Indolent systemic mastocytosis 


 
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I TI M 
I m m u n orec e pt or t yr osi ne-base d i n hi bit or y m otif  
I T T 
I nt e nt t o tre at 
I U D 
I ntra ut eri ne de vi ce 
I V 
I ntra ve n o us 
k g 
Kil o gra m 
K R 2  
Ke n war d -R o d ger’s m et h o d  
L A R C  
L o n g- a cti n g re versi ble c o ntr ac e pti ves  
L L N  
L o wer li mit of n or m al  
L S M  
L east s q uare m ea n (s) 
M A R  
Missi n g at ra n d o m  
Me d D R A  
Me dic al Dicti o nar y f or Re g ulat or y Acti viti es  
m g  
Milli gra m  
MI  
M ulti ple i m p ut ati o n 
MI U  
Milli -i nt er nati o nal u nits 
m L  
Millilit er  
m M  
Milli m ol ar  
M M R M  
Mi xe d m o del f or re pe at e d me as ures  
M N A R  
Missi n g n ot at ra n d o m  
M T D  
Ma xi m u m t olerat e d d ose  
Na Cl  
S o di u m c hl ori de  
N CI  
Nati o nal Ca nc er I nstit ut e  
N C S  
N ot cli nic all y si g nific a nt  
N C T  
Nati o nal Cli ni cal Tri al (I de ntifi er)  
N O A E L  
N o -o bser ve d -a d verse -effect le vel 
O & P  
O va a n d p arasit e (test) 
O L E  
O pe n -la bel e xt e nsi o n  
P C S  
P h ysi c al c o m p o ne nt sc ore  
P D  
P har ma c o d y na mics  
P D F  
Pr o ba bilit y distri b uti o n f u ncti o n  
P E F  
Pe a k e x pirat or y fl o w  
 
 
 
  
PI D  
Patie nt i de ntifi cati o n n u m ber  
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 1 4 of 1 4 0 
C o nfi de nti al  
P K  
P har ma c o ki neti c(s)  
P P  
Per Pr ot oc ol  
P PI  
Pr ot o n p u m p i n hi bit or  
P R O  
Patie nt re p orte d o utc o m e  
S A E  
Seri o us a d verse e ve nt(s) 
S A P  
St atistic al A nal ysis Pla n  
S E  
St a n dar d err or(s)  
 
 
Si gl ec  
Si ali c aci d -bi n di n g, i m m u n o gl o b uli n -li ke le cti n 
S O C  
S yst e m or ga n cl ass  
S O P  
St a n dar d o perati n g pr oc e d ure(s)  
T E A E  
Treat m e nt -e mer ge nt a d verse e ve nt (s) 
T E A E SI  
Treat m e nt -e mer ge nt a d verse e ve nt (s) of s pe ci al i nterest  
T N F  
T u m or ne cr osis fa ct or  
T S S  
T otal s y m pt o m sc ore  
T S S 8  
T otal S y m pt o m S c ore o n 8 ite ms 
U L N  
U p per li mit of n or mal 
U S P  
U nit e d States P har m ac o pei a  
W H O D D  
W orl d He alt h Or ga niz ati o n Dr u g Dicti o nar y  
W O C B P  
W o me n of c hil d be ari n g p ot e ntial  
w/ v  
W ei g ht/ v ol u me 
C CI


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 15 of 140 
Confidential 
1. 
Protocol Synopsis 
Study Title: 
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Efficacy and Safety of AK002 in Patients with Moderate to Severe 
Active Eosinophilic Duodenitis who have an Inadequate Response with, Lost 
Response to, or were Intolerant to Standard Therapies 
Sponsor: 
Allakos Inc, 825 Industrial Road, Suite 500, San Carlos, CA 94070 USA 
Number of Sites: Approximately 35 clinical centers in the United States. 
Nonclinical Background  
AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed 
against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like 
lectins (Siglecs).  
Siglec-8 has a restricted tissue distribution, expressed selectively on the surface of mature eosinophils 
and mast cells, but not in early precursors of these cell populations. In blood, binding of AK002 to 
Siglec-8 induces antibody-dependent cellular cytotoxicity (ADCC) against eosinophils, leading to rapid 
and sustained depletion of these cells from the circulation. In the tissue, AK002 induces direct apoptosis 
of eosinophils and inhibition of mast cells.  
Clinical Background 
AK002, administered as an intravenous infusion, has been previously tested in healthy volunteers and in 
patients with indolent systemic mastocytosis (ISM), chronic urticaria (CU), severe allergic conjunctivitis 
(AC), mast cell gastritis, and eosinophilic gastritis (EG) and/or eosinophilic duodenitis (EoD), which was 
referred to as eosinophilic gastroenteritis (EGE) in previous studies. Multiple doses of 3 mg/kg have been 
given to patients with ISM, CU, severe AC, EG, and/or EoD. In these studies, patients reported 
improvements in disease symptoms, with AK002 pharmacodynamic (PD) activity being observed for 
prolonged periods of time and pharmacokinetic (PK) parameters demonstrating a half-life amenable to 
administration every 4 weeks.  
To date, over 700 healthy volunteers and patients with ISM, CU, severe AC, EG/EoD, eosinophilic 
esophagitis (EoE), and mast cell gastritis have received AK002 in clinical studies. In general, AK002 has 
been well tolerated. The most common treatment-emergent adverse events (TEAE) observed were 
infusion-related reactions (IRR). Most IRR were mild to moderate and many resolved on their own with 
no additional treatment required. IRR that were deemed more serious typically resolved within 24 hours, 
and additional corticosteroids and/or antihistamines were used in cases when slowing the rate of infusion 
and additional supportive care alone did not resolve the issue. Transient lymphopenia was observed after 
infusion of AK002 but was not associated with any clinical consequence, and lymphocytes recovered 
within 24 hours. A sustained depletion of eosinophils was observed that is consistent with the mechanism 
of action of AK002.  
In the randomized, double-blind, placebo-controlled, Phase 2 study of AK002 in 65 patients with EG 
and/or EoD, patients were randomized to receive monthly doses of placebo, low dose AK002 (0.3, 1, 1, 
and 1 mg/kg), or high dose AK002 (0.3, 1, 3, and 3 mg/kg) in a 1:1:1 ratio (Dellon, 2020). 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 16 of 140 
Confidential 
Clinical Background cont. 
All primary and secondary endpoints were met in the study. There was a 97% and 92% mean reduction 
in eosinophils in the stomach/duodenum at the high dose and low dose, respectively, vs 10% increase for 
patients on placebo (p<0.0001).  
There was also a statistically significant reduction in total symptom score on 8 items (TSS8) of 58% in 
the high dose group and 49% in the low dose group vs 24% reduction in the placebo group (p=0.0012 
and p=0.015, respectively). Improvement in symptoms was observed within 24 hours of the first dose 
of study drug. In addition, 70% of high dose treated patients and 68% of low dose treated patients were 
treatment responders (defined as >30% improvement in Total Symptom Score (TSS) and >75% 
reduction from baseline in tissue eosinophils) vs 5% of placebo treated patients (p<0.0001) 
(Dellon, 2020).  
Among the 65 patients, there were patients with EG without EoD, patients with EoD without EG, and 
patients with both EG and EoD, and these subgroups had similar symptoms and symptom severity. The 
treatment benefit of AK002 was observed across all of the subgroups, whether eosinophilia was reported 
in the duodenum with or without concomitant EG.  
Patients with EoD without EG had similar histologic response on AK002 treatment as those with EG 
with or without EoD (All EG). AK002 treatment resulted in a -99.5% and -91.5% mean change in tissue 
eosinophils in patients with EoD and in patients with EG ± EoD, respectively. The proportion of patients 
achieving ≤1 eosinophil/high-power field (hpf) at the end of treatment was also similar (93.3% of EoD 
and 75% of EG ± EoD , respectively), compared to no patients on placebo. Additionally, symptomatic 
improvement was similar; EoD patients had a mean change in TSS of -57.4%, and EG ± EoD patients 
experienced a -51% mean change in TSS. 
Among patients with concomitant eosinophilic esophagitis (EoE) in this study, a mean reduction of 95% 
of eosinophils/hpf in esophageal biopsies for AK002 was observed vs no change for placebo. Also, 
13 of 14 AK002-treated patients (93%) were histologic responders as defined by ≤6 eosinophils/hpf vs 
1 of 9 placebo-treated patients (11%). Dysphagia improved by 53% in AK002-treated patients vs 17% 
in placebo-treated patients.  
More than 90% of patients in the Phase 2 study elected to continue into an open-label, long-term 
extension study (AK002-003X). In that study, a starting dose of 1 mg/kg AK002 was followed by doses 
of 3 mg/kg AK002. Premedication of 80 mg oral prednisone was administered the day before the first 
and second doses. Using this premedication regimen in the extension study, no IRR were reported on the 
first infusion of AK002. 
The proposed dose regimen of 6 total doses of 3 mg/kg AK002, administered every 4 weeks, is based on 
experience with AK002 in healthy volunteers and in patients with ISM, CU, severe AC, mast cell 
disease, EoE, and EG/EoD.  
The proposed dose of 3 mg/kg is based on experience across multiple prior studies, in which subjects 
received 60 mg prednisone as premedication followed by a dose of 3 mg/kg AK002 for the first infusion. 
This dosing regimen was well tolerated. By using this premedication regimen, the incidence and severity 
of IRR were substantially reduced. 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 17 of 140 
Confidential 
Target Disease Background and Rationale  
EoD represents a type of eosinophilic gastrointestinal disorder (EGID) that is characterized by chronic, 
often severe inflammation due to patchy or diffuse infiltration of eosinophils into layers of the duodenum 
(Prussin, 2014; Reed, 2015; Zhang, 2017).  
The diagnosis is based on clinical presentation (gastrointestinal symptoms) combined with increased 
tissue eosinophils in biopsy specimens from the duodenum ± the stomach without any other cause for the 
eosinophilia. Involvement of the small intestine is typically assessed by performing duodenal biopsies 
using an esophago-gastro-duodenoscopy (EGD) and has been referred to as eosinophilic gastroenteritis 
(EGE) or eosinophilic enteritis although eosinophilic duodenitis (EoD) is more appropriate.  
The gastrointestinal symptoms are believed to be due to the release of inflammatory mediators from 
activated eosinophils. However, emerging evidence suggests that activated mast cells also contribute to 
disease. Symptoms that are often debilitating commonly include abdominal pain, nausea, bloating, early 
satiety, loss of appetite, abdominal cramping, vomiting, diarrhea, and weight loss (Alhmoud, 2016; 
Lopez-Medina, 2015; Mansoor, 2017; Reed, 2015).  
Jensen (2016) estimated the prevalence of EG and EoD to be 6.3/100,000 and 8.4/100,000, respectively 
(for patients from 1 to 64 years of age). Mansoor (2017) estimated the overall prevalence of EG to be 
5.1/100,000 persons, though emerging evidence suggests that true prevalence is higher (Licari, 2020). 
More recently, a prevalence study was conducted in which 556 patients with chronic (≥6 months) 
gastrointestinal (GI) symptoms, unresponsive to pharmacologic/dietary interventions, and/or a historical 
diagnosis of irritable bowel syndrome or functional dyspepsia were screened. Four hundred five patients 
met symptom-severity criteria and were evaluated by EGD with standardized collection of biopsies for 
histopathology evaluation. Of those enrolled, 181 (45%) met histologic criteria for EG and/or EoD, and 
of the 181 patients, 122 (67%) were EoD-only patients (AK002-019 data on file).  
There are no FDA-approved treatments for EoD. Current therapies and disease management include 
dietary restriction/elimination, proton pump inhibitors (PPI), antihistamines, systemic or swallowed 
corticosteroids, and occasional off-label use of immunomodulatory biologics (Prussin, 2014; Reed, 2015; 
Zhang, 2017). Proton pump inhibitors have little to no benefit in patients with EoD despite reports of 
providing partial benefit in some patients with EoE (Katz, 2013). Restricted/elemental diets are not 
effective long-term treatment as they require strict compliance and, in the case of elemental diets, are 
expensive and are often not reimbursed by insurance. In addition, compliance is poor and patient quality 
of life is greatly impacted (Bedell, 2018; Peterson, 2013; Wechsler, 2014). Corticosteroids, systemic or 
topical, have been shown to provide symptom relief but are not appropriate for long-term treatment due 
to numerous side effects and associated risks including adrenal insufficiency, bone demineralization, 
increased chance of infection, behavioral issues, weight gain, diabetes/glucose intolerance, and 
hypertension. 
By markedly reducing the number of blood and tissue eosinophils and inhibiting the activation of mast 
cells, AK002 can be useful in the treatment of patients with EoD. This premise is supported by the 
Phase 2 data with AK002 that shows significant improvements in histology and symptoms in these 
patients. Given there are no approved therapies for this chronic and debilitating disease, better treatment 
options are clearly needed. 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 1 8 of 1 4 0 
C o nfi de nti al  
R ati o n ale f or D ose  S electi o n  
T he pr o p ose d d ose re gi me n of 6 t otal d oses of 3 m g/ k g  A K 0 0 2, a d mi nistere d e ver y 4 wee ks is base d o n 
e x perie nce wit h A K 0 0 2 i n healt h y v ol u nteers a n d i n patie nts wit h I S M, C U, se vere A C, mast cell 
disease, E o E, a n d E G/ E o D.  
T he pr o p ose d d ose of 3 m g/ k g A K 0 0 2 is base d o n e x perie nce acr oss m ulti ple pri or st u dies, i n w hic h 
s u bjects recei ve d 6 0 m g of pre d nis o ne as pre me dicati o n, f oll o we d b y a d ose of 3 m g/ k g A K 0 0 2 f or t he 
first i nf usi o n. T his d osi n g re gi me n was well t olerate d. B y usi n g t his pre me dicati o n re gi me n, t he 
i nci de nce a n d se verit y of I R R were s u bsta ntiall y re d uce d. 
N u m b er of P atie nts  
A p pr o xi matel y 8 0 patie nts wit h m o deratel y t o se verel y acti ve E o D ( wit h o ut E G) will be ra n d o mize d 1: 1 
t o recei ve 1 of 2 treat me nt re gi me ns i n a d o u ble-bli n d fas hi o n:  
•  
6 d oses of place b o e ver y 4 wee ks.  
•  
6 d oses of A K 0 0 2 at 3 m g/ k g a d mi nistere d e ver y 4  wee ks.  
All patie nts will recei ve 8 0 m g pre d nis o ne t he da y bef ore t he first i nf usi o n. T he  rati o nale f or t he n u m ber 
of patie nts is descri be d u n der Statistical A nal ysis.  
St u d y Desi g n  
T his is a P hase 3, m ultice nter, ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d st u d y t o e val uate t he 
effica c y a n d safet y of A K 0 0 2 i n patie nts wit h E o D w h o ha ve a n i na de q uate res p o nse wit h, l ost res p o nse 
t o, or were i nt olera nt t o sta n dar d t hera pies. 
P atie nts e nr olle d i n t he st u d y will recei ve 6 i nf usi o ns of place b o or A K 0 0 2 a d mi nistere d e ver y 4 wee ks 
a n d will be f oll o we d f or 1 2 wee ks after last d ose. P atie nts w h o elect t o e nter t he o pti o nal l o n g -ter m 
e xte nsi o n ( O L E) peri o d of t he st u d y will be f oll o we d f or 5 wee ks u n der t he d o u ble -bli n d peri o d of t he 
st u d y bef ore e nteri n g t he O L E peri o d of t he st u d y. 
 
C CI


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 19 of 140 
Confidential 
Study Design cont. 
Patients will be consented and then screened for up to 45 days prior to Day 1. Patients who meet all 
eligibility criteria can be enrolled into the study. Patients 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. Patients rescreened within 30 days of signing the initial consent will not 
need to sign a new informed consent form (ICF) if no changes have been made to the ICF. 
Patients will undergo an EGD and colonoscopy with biopsy at screening and again 4 weeks after last 
dose. For patients with a history of EoE and/or with a score of ≥3 on the dysphagia question during 
screening, esophageal biopsies will also be collected at screening and postdose. Biopsies from the gastric 
mucosa, duodenum, colon, and esophagus (as applicable) will be taken and reviewed by a central 
pathology reader. Additional biopsies will be collected for exploratory analysis. 
The study is designed as follows: 
• 
A screening period of 21–45 days with baseline evaluations for study eligibility, including active 
symptoms of disease (gathered by the patient reported outcome [PRO] questionnaire completed 
during screening) and EGD and colonoscopy with biopsy. 
• 
Stool antigen test for Helicobacter pylori (H. pylori) will be assessed during screening to confirm no 
active H. pylori infection exists. If H. pylori is detected in tissue biopsies by the central pathologist, 
the patient should be excluded from the study. 
• 
Prior EGD and colonoscopy biopsy samples may be used for eligibility as long as they were 
performed within 45 days of the AK002-021 screening window for the AK002-021 study and were 
performed and centrally assessed using the same criteria as for AK002-021 study.  
• 
If patients meet histology and symptom eligibility criteria, they will be randomized and stratified by 
the highest weekly TSS of disease activity recorded during the screening period (<28 or ≥28 strata). 
The interactive response technology system (IRT) will assign patients 1:1 to receive 6 doses of 
placebo or AK002. 
• 
Electronic PRO scores from the day before and day of colonoscopy will be excluded from the TSS 
since the bowel prep could artificially increase the scores. 
• 
Prestudy medications and dietary restrictions should remain unchanged throughout the screening 
period and throughout the study. Systemic or topical corticosteroids above 10 mg prednisone daily 
(or the equivalent thereof) will not be allowed, except as a premedication prior to the first infusion 
only, or to treat an IRR that occurs during infusion, or for unforeseen circumstances when it is 
deemed to be medically necessary to treat an unrelated medical condition. 
• 
Eligible patients will receive the first dose of placebo or AK002 (3 mg/kg) on Day 1 with 
premedication of 80 mg oral prednisone 12–24 hours prior to the start of the infusion.  
• 
If the study drug is well tolerated (no stopping rules being met), patients will receive additional doses 
of placebo or AK002 (3 mg/kg) on Days 29, 57, 85, 113, and 141. With the exception of Day 1, 
steroid premedication will only be allowed with the written approval of the Medical Monitor.  
 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 2 0 of 1 4 0 
C o nfi de nti al  
St u d y Desi g n c o nt.  
•  
P atie nts will re mai n at t he site f or at least 1 h o ur of o bser vati o n f oll o wi n g t he e n d of t he i nf usi o n.  
•  
A n E G D a n d c ol o n osc o p y wit h bi o ps y will be perf or me d o n Da y 1 6 9 ( ± 3) or 2 8 ( ± 3) da ys after  t he 
last d ose of st u d y dr u g if t he patie nt ter mi nates earl y fr o m t he st u d y. 
•  
Dail y a d mi nistrati o n of t he P R O q uesti o n naire f or all patie nts.  
•  
P atie nts will rate t heir i m pressi o n of disease se verit y  
 a n d disease i m pr o ve me nt  
 at 
s pecifie d ti me p oi nts d uri n g t he st u d y.  
•  
P atie nts 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 d ys p ha gia a n d c o nsti pati o n o n a dail y 
basis d uri n g scree ni n g a n d t hr o u g h o ut t he st u d y. T hese will be c o m plete d f oll o wi n g t he P R O 
q uesti o n naire. 
•  
F oll o w- u p will occ ur f or 8 4 ( ± 3) da ys after last d ose of st u d y dr u g u nless patie nts dec i de t o e nter t he 
l o n g-ter m O L E peri o d of t he st u d y. F oll o w-u p visits f or patie nts o pti n g n ot t o e nter t he O L E peri o d 
of t he st u d y will occ ur o n Da y 1 7 6 ( ± 3), Da y 1 9 7 ( ± 3), a n d Da y 2 2 5 ( ± 3).  
•  
P atie nts w h o recei ve all 6 d oses of st u d y dr u g ha ve t he o pti o n t o recei ve A K 0 0 2 b y e nteri n g i nt o t he 
O L E peri o d of t he st u d y if all eli gi bilit y criteria f or t he O L E peri o d are satisfie d. P atie nts w h o e nter 
i nt o t he O L E peri o d of t he st u d y ma y be gi n t he e xte nsi o n d osi n g 1 da y after c o m pleti n g t he Da y 1 7 6 
visit of t his pr o t oc ol. O pe n-la bel e xte nsi o n patie nts will n ot c o m plete t he Da y 1 9 7 or Da y 2 2 5 
pr oce d ures u n der t he d o u ble -bli n d peri o d of t he st u d y.  
•  
Eli gi ble patie nts w h o c h o ose t o partici 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 S c he d ule 
of Assess me nts (Ta ble  8 i n A p pe n di x 1 3 ) a n d ma y recei ve t he first d ose of o pe n-la bel A K 0 0 2 after 
t he Da y 1 7 6 visit i n t he d o u ble-bli n d peri o d of t he st u d y has occ urre d.  
•  
T he s u bject will f oll o w t he visits a n d pr oce d ures of t he d o u ble -bli n d peri o d of t he st u d y u ntil starti n g 
t he O L E peri o d of the st u d y.  
•  
T otal st u d y d urati o n is a p pr o xi matel y 3 5 – 3 7 wee ks. F or patie nts e nteri n g t he O L E peri o d of t he 
st u d y, t he t otal st u d y d urati o n will be a n a d diti o nal 2 8– 3 0 wee ks.  
Pri m ar y O bjecti ves  
T o e val uate t he efficac y a n d safet y of 6 d oses of A K 0 0 2 i n patie nts wit h m o derate t o se vere E o D w he n 
c o m pare d wit h place b o. Efficac y will be e val uate d b y t he f oll o wi n g c o -pri mar y e n d p oi nts:  
1) 
Pr o p orti o n of tiss ue e osi n o p hil res p o n ders at Wee k 2 4 . A res p on der is a patie nt ac hie vi n g a mea n 
d u o de nal e osi n o p hil c o u nt ≤1 5 cells/ h pf i n 3 hi g hest d u o de nal h pf.  
2) 
C ha n ge i n T S S fr o m baseli ne t o Wee ks 2 3– 2 4 as meas ure d b y t he P atie nt R e p orte d O utc o me ( P R O) 
q uesti o n naire.  
T he P R O T S S is c o m prised of  t he f oll o wi n g 6 s y m pt o ms:  
 
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 2 1 of 1 4 0 
C o nfi de nti al  
Pri m ar y O bjecti ves c o nt.  
•  
A b d o mi nal pai n i nte nsit y  
•  
Na usea i nte nsit y  
•  
F ull ness bef ore meal i nte nsit y  
•  
L oss of a p petite i nte nsit y  
•  
Bl oati n g i nte nsit y  
•  
A b d o mi nal cra m pi n g i nte nsit y  
S afet y will be e val uate d b y A E re p orti n g, la b orat or y safet y tests, c ha n ges i n vital si g ns, c ha n ges 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 para meters.  
S ec o n d ar y O bjecti ves  
T o f urt her c haracteriz e t he efficac y of A K 0 0 2 i n patie nts wit h E o D as meas ure d b y:  
•  
P erce nt c ha n ge i n tiss ue e osi n o p hils fr o m baseli ne t o Wee k 2 4.  
•  
Pr o p orti o n of patie nts ac hie vi n g mea n e osi n o p hil c o u nt of ≤1  cell/ h pf i n 3 hi g hest d u o de nal h pf at 
Wee k 2 4.  
•  
P r o p orti o n of treat me nt res p o n ders at Wee ks 2 3– 2 4. A r es p o n der is defi ne d as > 3 0 % i m pr o ve me nt i n 
T S S a n d mea n e osi n o p hil c o u nt ≤1 5 cells/ h pf i n 3  hi g hest d u o de nal h pf.  
•  
Pr o p orti o n of patie nts w h o s h o w ≥5 0 % re d ucti o n i n T S S fr o m baseli ne t o Wee ks 2 3 – 2 4.  
•  
Pr o p o rti o n of patie nts w h o s h o w ≥7 0 % re d ucti o n i n T S S fr o m baseli ne t o Wee ks 2 3– 2 4.  
•  
P erce nt c ha n ge i n wee kl y T S S o ver ti me.  
E x pl or at or y O bjecti ves  
T o e val uate t he effect of A K 0 0 2 b y c o m pari n g A K 0 0 2 t o place b o treat me nt f or t he f oll o wi n g para meters:  
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me. 
•  
C ha n ges i n 
 fr o m baseli ne c o m pare d t o p ost-treat me nt i n t he 
 
 will be n ote d. 
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me. 
•  
C ha n ge fr o m baseli ne i n  
 o ver ti me.  
St u d y P o p ul ati o n  
A p pr o xi matel y 8 0 a d ult male a n d fe male patie nts wit h m o deratel y t o se verel y acti ve E o D wit h o ut E G 
wit h i na de q uate or l oss of res p o nse t o, or i nt olera nce t o sta n dar d t hera pies.  
P atie nt S electi o n Criteri a  
I n cl usi o n Criteri a 
P atie nts are eli gi ble t o e nr oll i n t he st u d y if all of t he f oll o wi n g criteria are met:  
C CI
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Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 22 of 140 
Confidential 
Patient Selection Criteria – Inclusion Criteria cont. 
1) 
Provide written informed consent. 
2) 
Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry. 
3) 
Baseline endoscopic biopsy with ≥30 eosinophils/hpf in at least 3 hpf in the duodenum as 
determined by central histology assessment of biopsies collected during the screening EGD without 
any other significant cause for the eosinophilia. 
4) 
Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during 
screening. 
5) 
A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the PRO questionnaire (score 
from 0–10) for at least 2 weeks of screening and a weekly average TSS of ≥10 for at least 2 weeks 
of screening.  
6) 
Patients with inadequate or loss of response to, or who were intolerant to standard therapies for EoD 
symptoms, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, 
among others. 
7) 
If patient is on preexisting dietary restrictions, willingness to maintain dietary restrictions 
throughout the study. 
8) 
Willing and able to comply with all study procedures and visit schedule including follow-up visits. 
9) 
Female patients must be either post-menopausal for at least 1 year with FSH level >30 MIU/mL at 
screening or surgically sterile (tubal ligation, partial or total hysterectomy, or bilateral 
oophorectomy) for at least 3 months, or if of childbearing potential, have a negative pregnancy test 
and agree to use dual methods of contraception, have a partner who had a vasectomy, or agree to 
abstain from sexual activity from screening until the end of the study or for 120 days following last 
dose of study drug, whichever is longer. 
 
Non-vasectomized male patients with female partners of childbearing potential must agree to either 
abstain from sexual activity or agree to use a highly effective method of contraception from 
screening until the end of the study or for 120 days following last dose of study drug, whichever is 
longer. All fertile men with female partners of childbearing potential should be instructed to contact 
the Investigator immediately if they suspect their partner might be pregnant (e.g., missed or later 
menstrual period) at any time during study participation. 
Exclusion Criteria 
Patients will be excluded from the study if they meet any of the following criteria: 
1) 
Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone 
within 4 weeks prior to the screening visit. 
2) 
Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the gastric mucosa, as determined 
by central histology assessment of biopsies collected during the screening EGD. 
3) 
Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 
4 weeks prior to the screening visit. 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 23 of 140 
Confidential 
Patient Selection Criteria – Exclusion Criteria cont. 
4) 
Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the 
study within 12 weeks prior to the screening visit. 
5) 
Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug. 
6) 
Active H. pylori infection as confirmed by stool antigen test for H. pylori.  
7) 
History of inflammatory bowel disease, other chronic inflammatory diseases in the colon (with the 
exception of eosinophilic colitis), celiac disease, achalasia, or esophageal surgery. 
8) 
History of bleeding disorders and/or esophageal varices considered to be clinically significant by the 
Investigator.  
9) 
Other significant causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with 
polyangiitis (EGPA). 
10) Confirmed diagnosis of hypereosinophilic syndrome (HES). 
11) Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the 
study. 
12) Presence of an abnormal laboratory value considered to be clinically significant by the Investigator. 
13) Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the 
Investigator, would place the patient at increased risk. 
14) History of malignancy, except carcinoma in situ, early-stage prostate cancer, or non-melanoma skin 
cancers. However, patients with cancers that have been in remission for more than 5 years and are 
considered cured can be enrolled. 
15) Treatment for a clinically significant helminthic parasitic infection within 6 months of screening. 
16) Positive helminthic infection on ova and parasite (O&P) test.  
17) Seropositive for Strongyloides stercoralis at screening. 
18) Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past 
but resolved hepatitis, at screening. See Appendix 12 for details on Hepatitis B and Hepatitis C 
serologic testing. 
19) Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, 
during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug 
administration. This exclusion criterion does not apply to all types and formulations of vaccines 
authorized by FDA or other regulatory authority for the prevention of COVID-19, which may be 
administered before, during, or after the study. The vaccine should not be administered within 
7 days prior to and within 7 days after the administration of AK002 so that any side effects caused 
by either of the 2 medications can be more easily determined. 
20) Participation in a concurrent interventional study with the last intervention occurring within 30 days 
prior to study drug administration or 90 days or 5 half-lives, whichever is longer, for biologic 
products. 
 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 2 4 of 1 4 0 
C o nfi de nti al  
P atie nt S electi o n Criteri a – E xcl usi o n Criteri a c o nt.  
2 1) K n o w n hist or y of alc o h ol, dr u g, or ot her s u bsta nce a b use or de pe n de nce t hat is c o nsi dere d b y t he 
I n vesti gat or t o be o n g oi n g a n d cli nicall y si g nifica nt. 
2 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 t he Me dical M o nit or ma kes t he patie nt 
u n s uita ble f or e nr oll me nt. 
Test Pr o d u ct, D ose, a n d A d mi nistr ati o n  
A K 0 0 2 ( 
) a n d place b o are s u p plie d as sterile li q ui ds a n d will be dil ute d wit h 0. 9 % Na Cl f or 
i ntra ve n o us i nf usi o n. T he i nf usi o n will be a d mi nistere d as s pecifie d i n t he P har mac y Ma n ual.  
A K 0 0 2 a n d place b o are f or m ulate d i n 
 
 p H 6. 0, i n Water f or I njecti o n ( W FI). 
P atie nts will self -a d mi nister 8 0 m g oral pre d nis o ne or a n alter nati ve pre me dicati o n a p pr o ve d b y t he 
Alla k os Me dical M o nit or 1 2 – 2 4 h o urs pri or t o t he first i nf usi o n o nl y. A ster oi d pre me dicati o n pri or t o 
t he start of t he sec o n d t hr o u g h si xt h i nf usi o ns ma y o nl y be a d mi nistere d wit h t he pri or writte n a p pr o val 
of t he Me dical M o n it or. 
A K 0 0 2 at a d ose of 3  m g/ k g or place b o will be pre pare d acc or di n g t o t he patie nt’s b o d y wei g ht a n d 
a d mi nistere d o n Da y 1. S u bse q ue nt i nf usi o ns of A K 0 0 2 at a d ose of 3 m g/ k g or place b o acc or di n g t o t he 
patie nt’s b o d y wei g ht will be pre pare d o n Da y  2 9 ( ± 3), Da y 5 7 ( ± 3), Da y 8 5 ( ± 3), Da y 1 1 3 ( ± 3), a n d 
Da y  1 4 1 ( ± 3). T he i nitial i nf usi o n s h o ul d be gi ve n o ver at  least a 4-h o ur peri o d, a n d t he s u bse q ue nt 
i nf usi o ns s h o ul d be gi ve n o ver at least a 1-h o ur peri o d, de pe n di n g o n t he patie nt’s t olera nce of t he 
pre vi o us i nf usi o ns a n d at t he I n vesti gat or’s discreti o n. R efer t o t he P har mac y Ma n ual f or all i nf usi o n 
rates.  
A n y re d ucti o n i n t he i nf usi o n rate d ue t o t olera bilit y will n ot be c o nsi dere d a de viati o n fr o m t he pr ot oc ol. 
All i nf usi o ns m ust be c o m plete d wit hi n 8 h o urs of t he st u d y dr u g bei n g mi xe d wit h Na Cl.  
D u r ati o n of S u bject P artici p ati o n  
T he t otal st u d y d urati o n f or eac h patie nt will be a p pr o xi matel y 8 m o nt hs, w hic h i ncl u des:  
•  
A scree ni n g peri o d of 2 1 – 4 5 da ys pri or t o st u d y dr u g a d mi nistrati o n.  
•  
A treat me nt peri o d of 2 0 wee ks.  
•  
A f oll o w -u p peri o d of 8 4 ( ± 3) da ys after last d ose of st u d y dr u g.  
•  
P atie nts w h o e nter t he O L E peri o d of t he st u d y will partici pate i n t he d o u ble -bli n d peri o d of St u d y 
A K 0 0 2 -0 2 1 f or 2 6 – 3 2 wee ks a n d will c o m plete t he st u d y at least t hr o u g h t he  Da y 1 7 6 visit.  
•  
P atie nts w h o e nter t he O L E peri o d pri or t o Da y 1 9 7 will n ot c o m plete t he Da y 1 9 7 visit or Da y  2 2 5 
visit of t he d o u ble -bli n d st u d y peri o d b ut will i nstea d f oll o w t he O L E sc he d ule of e ve nts ( Ta ble  8) 
t hr o u g h Da y 3 7 3. 
•  
T he patie nt will f oll o w t he visits a n d pr oce d ures of t he d o u ble -bli n d peri o d of t he st u d y u ntil starti n g 
t he O L E peri o d of t he st u d y. 
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 2 5 of 1 4 0 
C o nfi de nti al  
S afet y E v al u ati o ns  
S afet 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 c o m plicati o ns res ulti n g fr o m t he i ntra ve n o us i nf usi o n. All T E A E will be c ollecte d fr o m t he start of 
st u d y dr u g a d mi nistrati o n t hr o u g h st u d y c o m pleti o n or earl y ter mi nati o n ( E T).  
S e verit y will be assesse d usi n g t he Nati o nal C a 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), versi o n 5. 0 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 f o r cli nical si g nifica nce a n d relati o ns hi p t o st u d y dr u g. 
A d diti o nal safet y e val uati o ns i ncl u de cli nical la b orat or y tests c o m prisi n g a nti -dr u g a nti b o d y ( A D A) t o 
A K 0 0 2, c o m plete bl o o d c o u nts, c he mistries a n d uri nal yses, 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 safet y data t hr o u g h o ut t he st u d y. C ertai n safet y data ( p ost -treat me nt 
cell differe ntials as well as tiss ue e osi n o p hil a n d mast cell c o u nts) 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 bias. T he 
desi g nate d S afet y M o nit or 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 he Me dical M o nit or, as nee de d, i n a ma n ner t hat d oes n ot ca use bias.  
A n i n de pe n de nt Data M o nit ori n g C o m mittee (i D M C) has bee n c o n ve ne d a n d will meet at re g ularl y 
sc he d ule d i nter vals i n acc or da nce wit h t he i D M C c harter. 
Effic ac y a n d P h ar m ac o d y n a mic E v al u ati o ns  
Dail y self -a d mi nistrati o n of a disease-s pecific patie nt q uesti o n naire, t he E osi n o p hilic 
Gastritis/ D u o de nitis P R O ( A p pe n di x 1 ), will be use d t o e val uate si g ns a n d s y m pt o ms ass ociate d wit h 
E o D. P atie nt T S S will be e val uate d, ca pt uri n g t he 6 c o m m o n s y m pt o ms of E o D (a b d o mi nal pai n, na us ea, 
a b d o mi nal cra m pi n g, l oss of a p petite, f ull ness bef ore fi nis hi n g a meal [earl y satiet y], a n d bl oati n g). 
V o miti n g a n d diarr hea will als o be ca pt ure d b ut will n ot be i ncl u de d i n t he T S S. I n a d diti o n t o t he P R O, 
patie nts will a ns wer 1  dail y q uesti o n eac h a b o ut d ys p ha gia a n d c o nsti pati o n.  
Bi o psies of t he gastric, d u o de nal m uc osa a n d c ol o n c ollecte d d uri n g pre -treat me nt a n d p ost-treat me nt 
E G D a n d c ol o n osc o p y will be e val uate d f or n u m ber of e osi n o p hils. I n a d diti o n, t he n u m ber of 
e osi n o p hils i n es o p ha geal m uc osa will be e val uate d i n patie nts wit h c o nc o mita nt E o E. 
 
 will be e val uate d pri or t o eac h i nf usi o n a n d 1 h o ur ( ± 1 5 mi n utes) after t he e n d 
of eac h i nf usi o n.  
P atie nts will be as ke d q uesti o ns a b o ut t he i nte nsit y of d ys p ha gia a n d c o nsti pati o n dail y, d uri n g scree ni n g 
a n d t hr o u g h o ut t he st u d y. P atie nts will rate t heir q ualit y of life usi n g t he n o n -disease -s pecific 
 
(A p pe n di x 2 ) at vari o us st u d y visits. P atie nts will rate t heir i m pressi o n of disease se verit y  
 
A p pe n di x 8 ) a n d disease i m pr o ve me nt  
, A p pe n di x 9 ) at s pecifie d ti me p oi nts d uri n g t he st u d y. 
P h ar m ac o ki n etic a n d A nti -Dr u g -A nti b o d y E v al u ati o ns  
Bl o o d (ser u m) will be c ollecte d f or assess me nt of A K 0 0 2 c o nce ntrati o ns usi n g a vali date d e nz y me -
li n ke d i m m u n os or be nt assa y ( E LI S A) met h o d. P har mac o ki netic ( P K) bl o o d sa m ples will be o btai ne d o n 
Da ys 8, 1 5, 2 9, 5 7, 8 5, 1 1 3, 1 4 1, 1 6 9, 1 7 6, 1 9 7, a n d 2 2 5 or 2 8, 3 5, 5 6, a n d 8 4 ( ± 3) da ys after last d ose of 
st u d y dr u g, if E T. O n d osi n g da ys ( Da ys 1, 2 9, 5 7, 8 5, 1 1 3, a n d 1 4 1), bl o o d f or P K will be c ollecte d 
pre d ose.  
C CI
C CI
C CI
C CI


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 26 of 140 
Confidential 
Pharmacokinetic and Anti-Drug-Antibody Evaluations cont. 
Blood (serum) will be collected for assessment of AK002 anti-drug antibodies (ADA) using a validated 
assay method. The ADA blood samples will be obtained at screening and predose on Days 1, 29, 57, 85, 
and 169, as well as on Day 225 or 84 (±3) days after last dose of study drug, if ET, and in the event of a 
suspected immunogenicity-related AE. 
Sample Size Calculation 
First Co-Primary Endpoint: A sample size of 40 patients per treatment group will have >90% power to 
demonstrate a greater proportion of histologic responders at Week 24 in AK002 patients when compared 
to placebo patients, assuming the proportions of histologic responders are 0.6 and 0.1 in the AK002 
group and placebo group, respectively.  
Second Co-Primary Endpoint: A sample size of 40 patients per treatment group will provide 80% 
power to detect a statistically significant difference of 7.4 points between AK002 and placebo in the 
mean reduction from baseline in TSS at Weeks 23–24, assuming a common standard deviation of 
12.5 points (AK002-003 data on file). 
Statistical Analysis 
The primary efficacy analysis population is the Evaluable Population defined as all randomized patients 
who have received at least 1 infusion of study drug and at study entry do not meet any of the following 
criteria: 
1) 
>6 eosinophils/hpf in at least 1 esophageal biopsy at baseline. 
2) 
Documented history of irritable bowel syndrome and baseline diarrhea intensity ≥3. 
The complement to the Evaluable population will be referred to as the Excluded population. It is worth 
remarking that for this study, if a patient has a history of concomitant EoE or if the esophagus looks 
suspicious for EoE or other condition, or if patient is symptomatic on screening dysphagia question, 
quantified by a score of >3 on the dysphagia question on at least 1 day during screening, then the 
following esophageal biopsies are collected during the baseline EGD: 
• 
A set of 2 fragments from the distal esophagus 
• 
A set of 2 fragments from the mid-proximal esophagus 
• 
Up to 2 extra specimens may be collected if there are any additional areas of interest. 
A count of >6 eosinophils/hpf in at least 1 esophageal site will be considered diagnostic for esophageal 
eosinophilia for the purposes of this study. In cases when there is a history of EoE, this could reflect 
active EoE although fulfillment of the diagnostic criteria for that condition may not be certain (see 
Appendix 5 for details). 
The Per Protocol (PP) population is defined as Evaluable population patients who received at least 
1 infusion of study drug and did not have significant protocol violations possibly interfering with 
assessment of efficacy. 
 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 27 of 140 
Confidential 
Statistical Analysis cont. 
The Safety population is defined as all patients who are randomized and have received at least 1 infusion 
of study drug. 
The Evaluable and Excluded populations will be used for all efficacy analysis. The Per Protocol 
population will be used for the primary endpoints and select secondary endpoints analyses. The Safety 
population will be used for all safety analysis. 
Patient disposition and reason for early discontinuation will be tabulated. Patient demographics, baseline 
characteristics, and treatment exposure will be summarized. 
Efficacy Analysis: To evaluate the clinical benefit of AK002 in adult patients with active EoD when 
compared with placebo, efficacy endpoints will be co-primary. 
The first co-primary endpoint will be analyzed using the Fisher’s exact test. Patients who experience an 
intercurrent event (ICE), i.e., exit the study prematurely or initiate prohibited or restricted medications, 
prior to the end of Week 24 will be treated as non-responders. Proportion of responders and the 
associated 95% confidence interval (CI) will be presented for each treatment group. The between-group 
difference and the associated 95% CI will also be computed and presented.  
Sensitivity analysis may be carried out using the Cochran-Mantel-Haenszel (CMH) test stratified by the 
randomization stratification factor (baseline TSS <28 vs ≥28) to assess the robustness of Fisher’s exact 
test results.  
The second co-primary endpoint will be analyzed using mixed model for repeat measures (MMRM) with 
treatment, week, treatment-by-week interaction, and baseline TSS-by-week interaction as fixed factors, 
gender, and baseline TSS (continuous) as covariates, and study site (with pooling by geographic location) 
as random effect. If the model does not converge with pooled sites as a random effect, it will be 
simplified with pooled site as a fixed effect. Details about the method for pooling sites will be provided 
in the statistical analysis plan (SAP).  
The weekly TSS is calculated as the average of the daily TSS. Weekly TSS will be set to missing if >3 
daily TSS are missing. Baseline TSS will be the average of the last 2 weeks of daily TSS collected prior 
to the first infusion. The model variance-covariance matrix will be unstructured. However, if 
computation does not converge, the matrix will take the form of Toeplitz, autoregressive, or compound 
symmetry, whichever converges first. 
Data on patients who experience an ICE, i.e., exit the study prematurely or initiate prohibited or 
restricted medications, prior to the end of Week 24 will be set to missing. If it is evident that the second 
co-primary endpoint is confounded by the influence of background variables, then the second co-primary 
analysis will be conducted adjusting for the effects of the background variables. Possible confounding 
factors may include age, presence of esophageal inflammation, history of IBS, and presence of diarrhea 
at baseline. 
 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 28 of 140 
Confidential 
Statistical Analysis cont. 
Two sensitivity analyses are planned. The first is a pattern-mixture model, where it will be assumed that 
AK002 subjects who experience an ICE will have a trajectory comparable to placebo post-ICE. This 
analysis will therefore provide a stress test of the missing at random (MAR) assumption of the MMRM 
employed in the principal analysis and will provide a conservative estimate of the treatment effect. 
The pattern-mixture model will be implemented using multiple imputations, and the inference of this 
sensitivity analysis will be based on the combined estimates using the standard multiple imputation 
technique. The imputed data sets will be analyzed with the same MMRM model utilized in the primary 
analysis and then summarized using PROC MIANALZE. The other is to analyze the average of Week 23 
through Week 24 using ANCOVA with treatment and study site (with pooling by geographic location) as 
factors, gender and baseline TSS (continuous) as covariates. Missing Week 23 through Week 24 weekly 
TSS will be imputed prior to ANCOVA using SAS PROC MI under the MAR assumption. Detailed 
specifications for the missing data imputation will be provided in the SAP.  
Analysis of binary secondary endpoints will be based on the CMH test stratified by the randomization 
stratification factor (baseline TSS <28 vs ≥28). 
Change from baseline in continuous secondary outcomes measured at multiple post-baseline time points 
will be analyzed longitudinally using MMRM techniques. The model will include fixed effects for 
baseline value, treatment, week, treatment by week interaction, baseline value by week interaction, and 
allow for random subject effects. The model variance-covariance matrix will be unstructured. However, 
if computation does not converge, the matrix will take the form of Toeplitz, AR(1), and compound 
symmetry, whichever converges first. 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. Least square means and the 95% CI for the between group difference will be 
estimated for each week. 
To control for the overall false-positive error rate, the hypothesis testing for the primary and secondary 
endpoints using the Evaluable population in the subgroup defined above as the only population for 
primary inference are ordered as follows: 
• 
The 2 co-primary efficacy endpoints will each be tested 2-sided at α=0.05 level. If both tests are 
statistically significant, the hypothesis tests for the secondary endpoints will proceed sequentially 
based on the order specified in Section 4.2. 
• 
If at any point the statistical test is not significant at 2-sided α=0.05 level, the hypothesis testing 
procedure will stop. All endpoints prior to this point will be considered statistically significant, and 
inferential statistics after this point will be considered descriptive. 
The estimand framework and the statistical methods will be further deliberated in the corresponding SAP 
as referenced to ICH Guidance E9 (R1) addendum (FDA, 2021), when appropriate.  
 
 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 29 of 140 
Confidential 
2. 
Background  
2.1 
Siglec-8 and AK002  
Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like 
lectins (Siglecs), is a transmembrane cell surface protein with restricted tissue distribution, 
expressed selectively on the surface of mature eosinophils and mast cells, but not in early 
precursors of these cell populations. Siglec-8 contains 3 extracellular immunoglobulin-like 
domains, a transmembrane region, and a cytoplasmic tail containing 2 tyrosine-based signaling 
motifs including an immunoreceptor tyrosine-based inhibitory motif (ITIM) with inhibitory 
function. Engagement of Siglec-8 in mast cells can result in inhibition of mediator release, and in 
eosinophils can induce apoptosis (Bochner, 2009). AK002 also shows potent antibody-dependent 
cellular cytotoxicity (ADCC) against eosinophils in vivo and in vitro. 
2.2 
Overview of Nonclinical Studies 
AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody 
directed against the inhibitory receptor Siglec-8, a member of the CD33-related family of 
Siglecs. 
Siglec-8 has a restricted tissue distribution, expressed selectively on the surface of mature 
eosinophils and mast cells, but not in early precursors of these cell populations. In blood, binding 
of AK002 to Siglec-8 induces ADCC against eosinophils, leading to rapid and sustained 
depletion of these cells from circulation. In the tissue, AK002 induces direct apoptosis of 
eosinophils and inhibition of mast cells. This profile of activity may provide clinical benefit in 
diseases in which these cell types play a role, such as eosinophilic gastritis and eosinophilic 
duodenitis.  
Siglec-8 is not expressed in species other than humans, and therefore, 2 novel mouse models 
have been developed for in vivo testing of AK002. AK002 has been studied in Siglec-8 
humanized and transgenic mouse models and with human blood and tissue cells. The first model 
uses immunodeficient mice capable of generating human immune cells including mast cells and 
eosinophils when engrafted with human hematopoietic stem cells. The ability of anti-Siglec-8 
antibodies to inhibit mast cell-mediated reactions has been evaluated in this model. The second 
rodent model is a transgenic mouse line that expresses human Siglec-8. The expression of 
Siglec-8 on the cell surface in these mice is restricted to eosinophils, mast cells, and basophils, a 
pattern of surface expression equivalent to that in humans. Anti-Siglec-8 antibodies can prevent 
IgE-mediated anaphylaxis in this transgenic mouse line, indicating that Siglec-8 is 
pharmacologically active in the model. The ability of AK002 to effect mast cells and eosinophils 
has been evaluated in this model. 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 30 of 140 
Confidential 
AK002 inhibits IgE-mediated mast cell degranulation and release of the newly formed mediator 
prostaglandin D2 in vitro without affecting mast cell viability. In peripheral blood preparations 
from normal human donors, AK002 shows selective depletion of eosinophils. Importantly, in a 
whole-blood cytokine-release assay using immobilized AK002 to enhance the potential for 
antibody crosslinking, AK002 did not lead to dose-dependent release of pro-inflammatory 
cytokines.  
To evaluate the in vivo activity of anti-Siglec-8 antibodies in an immunocompetent rodent 
model, a transgenic mouse strain has been developed that selectively expresses human Siglec-8 
on the surface of mouse mast cells, eosinophils, and basophils. In single-dose and repeat-dose 
studies in Siglec-8 transgenic mice, AK002 demonstrated selective depletion of peritoneal mast 
cells and circulating and tissue (spleen) eosinophils and basophils.  
In 2 Good Laboratory Practice (GLP) toxicity and toxicokinetic studies, AK002 was well 
tolerated at doses of 50 mg/kg and 100 mg/kg, 5-fold and 10-fold, respectively, the level of the 
highest dose proposed to be studied in humans. AK002 showed sustained systemic exposure in 
Siglec-8 transgenic mice with an extended terminal half-life estimated as 272 hours or 337 hours 
following single intravenous administration of 50 mg/kg or 100 mg/kg, respectively. There was 
no evidence of anti-drug antibodies (ADA) in either study. Decreases in eosinophil counts in 
both sexes were observed, which reflect the expected pharmacology of AK002. The no-
observed-adverse-effect-level (NOAEL) following intravenous administration of AK002 to 
transgenic mice was 100 mg/kg, which supports the Phase 1 studies in humans and is 
approximately 30 times the dose for this study, which is 3 mg/kg.  
2.3 
Overview of Clinical Studies 
AK002, administered as an intravenous infusion, has been previously tested in healthy volunteers 
and in patients with indolent systemic mastocytosis (ISM), chronic urticaria (CU), severe allergic 
conjunctivitis (AC), mast cell gastritis, eosinophilic esophagitis (EoE), and eosinophilic gastritis 
(EG) and/or eosinophilic duodenitis (EoD), which was previously referred to as eosinophilic 
gastroenteritis (EGE).  
Multiple doses of 3 mg/kg AK002 have been given to patients with ISM, CU, severe AC, mast 
cell gastritis, EoE, and EG and/or EoD. In these studies, patients reported improvements in 
disease symptoms with AK002 pharmacodynamic (PD) activity being observed for prolonged 
periods of time and AK002 pharmacokinetic (PK) parameters demonstrating a half-life amenable 
to administration every 4 weeks. 
To date, over 700 healthy volunteers and patients with ISM, CU, severe AC, EG/EoD, EoE, and 
mast cell gastritis have been enrolled in clinical studies.  


 
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In general, AK002 has been well tolerated. The most common treatment-emergent adverse 
events (TEAE) observed were infusion-related reactions (IRR). Most IRR were mild to 
moderate, and many resolved on their own with no additional treatment required. IRR that were 
deemed more serious typically resolved within 24 hours, and additional corticosteroids and/or 
antihistamines were used in cases when slowing the rate of infusion and additional supportive 
care alone did not resolve the issue. Common symptoms of IRR were headache, nausea, 
sweating, flushing, and redness. Most IRR that occurred during the infusion could be managed 
by slowing or temporary interruption of the infusion, with minimal intervention. In 6 healthy 
volunteers who received 2 doses of 0.3 mg/kg, 4 weeks apart, the second dose was better 
tolerated than the first dose. This is also the case in patients with ISM, CU, severe AC, and 
EG/EoD with fewer adverse events (AE) reported during the second and subsequent infusions 
when compared to the first infusion.  
In all studies there was a transient decrease in lymphocyte count after the AK002 infusion 
(usually resolving within 1 day) that was not associated with any clinical consequence and a 
sustained suppression in eosinophils that was consistent with the mechanism of action of AK002. 
No significant trends were observed for changes in vital signs, electrocardiograms (ECG), 
clinical laboratory parameters, or physical examinations. 
In the randomized, double-blind, placebo-controlled, Phase 2 study of AK002 in 65 patients with 
EG and/or EoD, patients were randomized to receive monthly doses of placebo, low dose AK002 
(0.3, 1, 1, and 1 mg/kg), or high dose AK002 (0.3, 1, 3, and 3 mg/kg) in a 1:1:1 ratio. All 
primary and secondary endpoints were met in the study. There was a 97% and 92% mean 
reduction in eosinophils in the stomach/duodenum for the high dose and low dose AK002-treated 
patients, respectively, vs a 10% increase for placebo-treated patients (p<0.0001). There was also 
a statistically significant reduction in total symptom score (TSS) of 58% in the high dose AK002 
group and 49% reduction in the low dose group AK002 vs a 24% reduction in the placebo group 
(p=0.0012 and p=0.015, respectively). Improvement in symptoms were observed within 24 hours 
of the first dose of study drug. In addition, 70% of high dose treated patients and 68% of low 
dose treated patients were treatment responders (defined as >30% improvement in TSS and 
>75% reduction from baseline in tissue eosinophils) vs 5% of placebo-treated patients 
(p<0.0001) (Dellon, 2020). 
Among the 65 patients, there were patients with EG without EoD, patients with EoD without EG, 
and patients with both EG and EoD, and these subgroups had similar symptoms and symptom 
severity. The treatment benefit of AK002 was observed across all of the subgroups, whether 
eosinophilia was reported in the duodenum with or without concomitant EG.  


 
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Patients with EoD without EG had a similar histologic response on AK002 treatment as those 
with EG with or without EoD (All EG). AK002 resulted in a -99.5% and -91.5% mean change in 
tissue eosinophils in patients with EoD without EG and in patients with EG ± EoD, respectively. 
The proportion of patients achieving ≤1 eosinophil/hpf at the end of treatment was also similar 
(93.3% and 75% of EoD without EG and All EG, respectively), compared to no patients on 
placebo. Additionally, symptomatic improvement was similar; EoD without EG patients had a 
mean change in TSS of -57.4%, and all EG patients experienced a -51% mean change in TSS. 
Approximately 40% of patients had concomitant EoE. In those patients, a mean reduction of 
95% of eosinophils/hpf in esophageal biopsies for AK002-treated patients was observed vs no 
change for placebo-treated patients. Also, 13 of 14 AK002-treated patients (93%) were histologic 
responders as defined by ≤6 eosinophils/hpf vs 1 of 9 placebo-treated patients (11%). Dysphagia 
improved by 53% in AK002-treated patients vs 17% in placebo-treated patients.  
More than 90% of patients in the Phase 2 study elected to continue into a long-term continuation 
study. In that study, a starting dose of 1 mg/kg was used, followed by subsequent doses of 
3 mg/kg. Premedication of 80 mg prednisone was administered the day before the first and 
second dose for 20 of the 58 patients dosed. Using this premedication regimen, no IRR were 
observed with the first infusion in the extension study.  
Study AK002-016 was a Phase 3, randomized, double-blind, placebo-controlled study of 
lirentelimab in subjects with moderate-to-severe EG/EoD. The study enrolled 180 subjects with 
EG and/or EoD. Subjects were required to be moderately to severely symptomatic based on a 
patient reported symptom questionnaire and to have biopsy-confirmed eosinophilia of the 
stomach (≥30 eosinophils/hpf in 5 hpf) and/or duodenum (≥30 eosinophils/hpf in 3 hpf). Subjects 
were randomized 1:1 to receive a monthly infusion of placebo or 1 mg/kg lirentelimab IV for the 
first month followed by 5 doses of 3 mg/kg lirentelimab administered monthly. Disease 
symptoms were measured daily using a patient-reported outcome (PRO) questionnaire (TSS6) 
that scored 6 symptoms (abdominal pain, nausea, bloating, early satiety, abdominal cramping, 
and loss of appetite), each on a scale from 0 to 10. Co-primary endpoints were the proportion of 
responders with ≤4 eosinophils/hpf in 5 hpf in the stomach and/or ≤15 eosinophils/hpf in 3 hpf in 
the duodenum at the end of Week 24, and the absolute change from baseline in TSS6 at 
Weeks 23–24. Subjects who completed Study AK002-016 had the option to receive lirentelimab 
in Study AK002-016X, an open-label extension (OLE) study. 
In this Phase 3 study, lirentelimab showed a statistically significant benefit compared to placebo 
on the histology co-primary endpoint but did not achieve statistical significance on the subject 
reported symptomatic co-primary endpoint (Table 1). 


 
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Table 1 
Study AK002-016 in Subjects with Moderate-to-Severe EG/EoD: 
Co-Primary Endpoints of Histology and Symptoms 
Co-Primary Endpoint 
Lirentelimab 
(n=89) 
Placebo 
(n=91) 
Co-Primary Endpoint – Histology 
 
 
Histology Endpoint: Proportion of responders as determined by gastric 
or duodenal tissue eosinophil count1 
84.6% 
4.5% 
p-value 
<0.001 
– 
Co-Primary Endpoint – Symptoms 
 
 
Baseline TSS 
29.5 
27.57 
Symptom Endpoint: Absolute mean change in subject reported TSS62 
-10.0 
-11.5 
p-value 
0.343 
– 
1) 
A responder is a subject achieving the following peak eosinophil counts: eosinophil count ≤4 cells/hpf in 
5 gastric hpf and/or eosinophil count ≤15 cells/hpf in 3 duodenal hpf. Endpoint assessed at end of Week 24. 
2) 
TSS6 is a daily PRO questionnaire assessing 6 symptoms (abdominal pain, nausea, bloating, early satiety, 
abdominal cramping, and loss of appetite) on a scale from 0 to 10. Endpoint was assessed as mean change from 
baseline to Weeks 23–24. 
When the change in TSS6 was analyzed for the Phase 3 AK002-016 study subjects enrolled at 
the sites that also participated in the Phase 2 AK002-003 study, the effect size as well as 
statistical significance for lirentelimab over placebo were consistent with the AK002-003 study 
(Figure 1). In contrast, when mean changes in TSS6 were analyzed separately for the Phase 3 
AK002-016 sites who did not participate in the Phase 2 AK002-003 study, there was no 
separation between lirentelimab and placebo for subject symptom scores. 
 
Left: Phase 2 Study AK002-003; Right: Phase 3 Study AK002-016 Sites that participated in AK002-003. 
Least squares means and p-values derived from ANCOVA/MMRM models. 
Figure 1 
Effects Observed in Subjects at Clinical Sites that Participated in Both 
AK002-003 and AK002-016 Studies 


 
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The proposed dose regimen of 6 total doses of 3 mg/kg AK002, administered every 4 weeks, 
is based on experience with AK002 in healthy volunteers and in patients with ISM, CU, severe 
AC, mast cell disease, EoE, and EG/EoD. The proposed dose of 3 mg/kg is based on experience 
across multiple prior studies, in which subjects received 60 mg prednisone as premedication 
followed by a dose of 3 mg/kg AK002 for the first infusion. This dosing regimen was well 
tolerated. By using this premedication regimen, the incidence and severity of IRR were 
substantially reduced. 
2.4 
Eosinophilic Gastrointestinal Disorders  
Eosinophilic gastrointestinal disorders (EGID) are chronic inflammatory disorders characterized 
by infiltration of eosinophils along different segments of the gastrointestinal tract, in the absence 
of any other cause of the eosinophilia (Caldwell, 2014). 
EG and/or EoD are traditionally believed to be rare types of EGID that are characterized by 
chronic, often severe inflammation due to patchy or diffuse infiltration of eosinophils into layers 
of the stomach, small intestine, or both the stomach and small intestine (Prussin, 2014; 
Reed, 2015; Zhang, 2017). The diagnosis is based on clinical presentation (gastrointestinal 
symptoms) combined with increased tissue eosinophils in biopsy specimens from the stomach 
and/or duodenum without any other cause for the eosinophilia. Involvement of the small intestine 
is typically assessed by performing duodenal biopsies using an esophago-gastro-duodenoscopy 
(EGD) and has been referred to as eosinophilic gastroenteritis or eosinophilic enteritis, though 
EoD is more accurate. The gastrointestinal symptoms are believed to be due to the release of 
inflammatory mediators from activated eosinophils, and also likely mast cells. Symptoms that 
are often debilitating commonly include abdominal pain, nausea, bloating, early satiety (fullness 
before finishing a meal), abdominal cramping, vomiting, diarrhea, and weight loss 
(Alhmoud, 2016; Lopez-Medina, 2015; Mansoor, 2017; Reed, 2015). 
Jensen et al. (2016) estimated the prevalence of EG and EoD to be 6.3/100,000 and 8.4/100,000 
respectively (for patients ages 1–64 years old). Mansoor et al. (2017) estimated the overall 
prevalence of EG to be 5.1/100,000 persons, though emerging evidence suggests that true 
prevalence is higher (Licari, 2020).  
More recently, a prevalence study was conducted in which 556 patients with chronic 
(≥6 months) gastrointestinal (GI) symptoms, unresponsive to pharmacologic/dietary 
interventions, and/or a historical diagnosis of irritable bowel syndrome or functional dyspepsia 
were screened. Four hundred five patients met symptom-severity criteria and were evaluated by 
EGD with standardized collection of biopsies for histopathology evaluation. Of those enrolled, 
181 (45%) met histologic criteria for EG and/or EoD. Of the 181 patients, 122 (67%) were 
EOD-only patients (AK002-019 data on file).  


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 3 5 of 1 4 0 
C o nfi de nti al  
T her e ar e n o F D A -a p pro ve d tr eat me nts f or E G a n d/ or E o D. C urre nt t hera pies a n d disease 
ma na ge me nt i ncl u de dietar y r estricti o n/eli mi nati o n, pr ot o n p u m p i n hi bit ors ( P PI ), 
a nti hista mi nes, s yste mic or t o pical c ortic oster oi ds, a n d occasi o nal off -la bel use of 
i m m u n o m o d ulat or y bi ol o gics ( Pr ussi n,  2 0 1 4; Ree d, 2 0 1 5 ; Z ha n g, 2 0 1 7 ). Pr ot o n p u m p i n hi bit ors 
ha ve little t o n o be nefit i n patie nts wit h E G a n d/ or E o D, des pite re p orts of pr o vi di n g partial 
be nef it i n s o me patie nts wit h E o E (Katz, 2 0 1 3 ). Restricte d/ele me ntal diets are n ot effecti ve l o n g-
ter m tr eat me nt as t he y r e q uir e strict c o m plia nce a n d, i n t he case of ele me ntal diets, are e x pe nsi ve 
a n d ar e ofte n n ot r ei m b urse d b y i ns ur a nce. I n  a d diti o n, c o m plia nce is p o or, a n d patie nt q ualit y of 
lif e is gr eatl y i m pacte d (Be dell, 2 0 1 8 ; Peters o n,  2 0 1 3; Wec hsler, 2 0 1 4 ). C ortic oster oi ds, 
s yste mic or t o pical (s wall o we d), ha ve bee n s h o w n t o pr o vi de s y m pt o m relief b ut are n ot 
a p pr o priate f or l o n g -ter m tr eat me nt d ue t o n u mer o us si de effects a n d ass ociate d ris ks i ncl u di n g 
a dr e nal i ns ufficie nc y, b o ne de mi ner alizati o n, i ncrease d c ha nce of i nfecti o n, be ha vi oral iss ues, 
wei g ht gai n , dia betes/ gl uc ose i nt oler a nce, a n d h y perte nsi o n .  
B y mar ke dl y r e d uci n g t he n u m ber of bl o o d a n d tiss ue e osi n o p hils a n d i n hi biti n g t he acti vati o n of 
mast cells, A K 0 0 2 ma y be usef ul i n t he treat me nt of patie nts wit h E G a n d/ or E o D. T his pre mise 
is s u p p orte d b y t he P hase 2 data wit h A K 0 0 2 t hat s h o ws si g nifica nt i m pr o ve me nt i n hist ol o g y 
a n d s y m pt o m se verit y i n t hese patie nts.  
Gi ve n t her e ar e n o a p pr o ve d t her a pies f or t hese c hr o nic a n d de bilitati n g diseases, bet ter 
tr eat me nt o pti o ns ar e clearl y nee de d t o ma na ge E G a n d E o D. 
3.  
R ati o n ale f or St u d y a n d D ose Selecti o n  
T he pr o p ose d d ose r e gi me n of 6 t otal d oses of 3 m g/ k g A K 0 0 2, a d mi nistere d e ver y 4 wee ks, is 
base d o n e x perie nce wit h A K 0 0 2 i n healt h y v ol u nteers a n d i n patie nts wit h I S M, C U, se vere A C, 
mast cell disease, E o E, a n d E G/ E o D.  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 3 6 of 1 4 0 
C o nfi de nti al  
T h er ef or e, t he pr o p ose d d osi n g r e gi me n f or t his P hase 3 st u d y wit h A K 0 0 2 i n patie nts wit h E o D 
wit h o ut E G will be a starti n g d ose of 3  m g/ k g A K 0 0 2 wit h 8 0 m g pre d nis o ne as a pre me dicati o n 
pri or t o t he first i nf usi o n o nl y, f oll o we d b y 5 d oses of 3  m g/ k g A K 0 0 2 f or s u bse q ue nt i nf usi o ns 
e ver y 4 wee ks.  
4.  
St u d y O bj ecti ves  
4. 1  
P ri m ar y O bj ecti ve  
T o e val uate t he efficac y a n d saf et y of 6 d oses of A K 0 0 2 i n patie nts wit h m o derate t o se vere E o D 
w he n c o m par e d wit h place b o.  
Efficac y will be e val uate d b y t he f oll o wi n g c o -pri mar y e n d p oi nts :  
1) 
Pr o p orti o n of tiss ue e osi n o p hil r es p o n ders at Wee k 2 4, w here a res p o n der is a patie nt 
ac hie vi n g a mea n d u o de nal e osi n o p hil c o u nt ≤1 5 cells/ h pf i n 3 hi g hest d u o de nal h pf.  
2)  
C ha n ge i n T S S fr o m baseli ne t o Wee ks 2 3 – 2 4 as meas ure d b y t he P R O q uesti o n nai re. 
T he P R O T S S is c o m prise d of t he f oll o wi n g 6 s y m pt o ms: 
•  
A b d o mi nal pai n i nte nsit y  
•  
Na usea i nte nsit y  
•  
F ull ness bef or e meal i nte nsit y  
•  
L oss of a p petite i nte nsit y  
•  
Bl oati n g i nte nsit y  
•  
A b d o mi nal cr a m pi n g i nte nsit y  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 3 7 of 1 4 0 
C o nfi de nti al  
Saf et y will be e val uate d b y A E r e p orti n g, la b orat or y safet y tests, c ha n ges i n vital si g ns, c ha n ges 
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 para meters. 
4. 2  
Sec o n d ar y O bj ecti ves  
T o f urt her c har acterize t he efficac y of A K 0 0 2 i n patie nts wit h E o D as meas ure d b y:  
•  
Per ce nt c ha n ge i n tiss ue e osi n o p hils fr o m baseli ne t o Wee k 2 4.  
•  
Pr o p orti o n of patie nts ac hie vi n g mea n e osi n o p hil c o u nt of ≤1 cell/ h pf i n 3 hi g hest d u o de nal 
h pf at Wee k 2 4.  
•  
P r o p orti o n of tr eat me nt r es p o n ders at Wee ks 2 3– 2 4. Res p o n der is defi ne d as > 3 0 % 
i m pr o ve me nt i n T S S a n d mea n e osi n o p hil c o u nt ≤1 5 cells/ h pf i n 3 hi g hest d u o de nal h pf.  
•  
Pr o p orti o n of patie nts w h o s h o w ≥5 0 % re d ucti o n i n T S S fr o m baseli ne t o Wee ks 2 3 – 2 4. 
•  
Pr o p ort i o n of patie nts w h o s h o w ≥7 0 % re d ucti o n i n T S S fr o m baseli ne t o Wee ks 2 3– 2 4. 
•  
Per ce nt c ha n ge i n wee kl y T S S o ver ti me.  
4. 3  
E x pl or at or y O bj ecti ves  
T o e val uate t he eff ect of A K 0 0 2 b y c o m pari n g A K 0 0 2 t o place b o treat me nt f or t he f oll o wi n g 
par a meters:  
•  
C ha n ge fr o m b aseli ne i n 
 o ver ti me. 
•  
C ha n ges i n 
 fr o m baseli ne c o m pare d t o p ost-treat me nt i n t he  
 
 will be n ote d. 
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me. 
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me. 
4. 4  
S af et y O bj ecti ves  
T o e val uate t he saf et y a n d t oler a bilit y of A K 0 0 2 b y deter mi ni n g i nci de nce a n d se verit y of A E, 
st u d y wit h dr a 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 nc o mita nt me dicati o n use d ue t o A E, a n d ot her safet y para meters. 
4. 5  
T ar get of Esti m ati o n  
T he esti ma n d (tar get of esti mati o n) f or Pr ot oc ol A K 0 0 2 - 0 2 1 is: 
 
I n p atie nts wit h E o D, w h at is bet wee n gr o u p ( A K 0 0 2 vs. Pl ace b o) differe nce i n t he 
pr o p orti o n of tiss ue e osi n o p hil res p o n ders  at Week 2 4, a n d gr o u p differe nce i n T S S fr o m 
b aseli ne t o W eeks 2 3 – 2 4 as me as ure d by t he P R O q uesti o n n aire.  
C CI
C CI
C CI
C CI
C CI


 
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Sections below describe the attributes of the estimand consistent with the ICH E9 Addendum 
(FDA, 2021). 
4.5.1 
Population Targeted by the Scientific Question 
The population targeted by the scientific question is defined by the inclusion and exclusion 
criteria as part of the study protocol. Patients must have a histological diagnosis of EoD. A key 
aspect of eligibility is that subjects must have a weekly average score of abdominal pain, nausea, 
or diarrhea ≥3 on the PRO questionnaire (score from 0–10) for at least 2 weeks of screening and 
a weekly average TSS of ≥10 for at least 2 weeks of screening. It is noted that history of 
inflammatory bowel disease, other chronic inflammatory diseases in the colon (with the 
exception of eosinophilic colitis), celiac disease, achalasia, or esophageal surgery is an 
exclusionary measure in the study. Supplementary analysis of data from the AK002-016 study 
focused on identification of baseline characteristics, which correlate with degree of change in 
TSS6 at Weeks 23–24. This examination identified 8 variables (age, gender, duodenal eosinophil 
counts, diarrhea frequency, history of IBS, abdominal pain, >6 esophageal eosinophils/hpf, and 
history of IBS in combination with diarrhea intensity ≥3) that most influenced the degree of 
change of the TSS6 endpoint. Two of the variables (>6 esophageal eosinophils/hpf and history of 
IBS in combination with diarrhea intensity ≥3) potentially reflect other disease states (IBS, 
GERD, or even active EoE) that could potentially impact multiple symptom components of 
TSS6. To ensure these 2 variables do not compromise the capacity to detect the treatment effect 
with symptoms of EoD as measured by the TSS6 questionnaire, the primary comparison of 
AK002 vs placebo will be conducted only on the Evaluable population defined as patients who 
do not meet any of the following criteria: 
1) 
>6 eosinophils/hpf in at least 1 esophageal site at baseline. 
2) 
Documented history of irritable bowel syndrome and baseline diarrhea intensity ≥3. 
4.5.2 
Variables of Interest (or Endpoint) Required to Address the Scientific Question 
The co-primary endpoints to be obtained for each subject in this study to address the scientific 
question are tissue eosinophil responders (as defined in Section 4.1) at Week 24 and change in 
TSS from baseline to Weeks 23–24 as measured by the PRO questionnaire. 
4.5.3 
Treatment 
AK002 or placebo administered to subjects on Days 1, 29, 57, 85, 113, and 141. 
4.5.4 
Intercurrent Events  
The events below are considered ICE confounding with the efficacy outcomes. 


 
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• 
Premature discontinuation from the study. 
• 
Use of prohibited/restricted medication. 
Further clarification and handling of ICE including prohibited/restricted medications will be 
detailed in the statistical analysis plan (SAP).  
4.5.5 
Strategy for Handling Intercurrent Events  
For the analysis of the trial product estimand, tissue eosinophil values and TSS will be counted 
as non-responders for binary variables and set to missing for continuous outcomes from the point 
when an ICE occurs. An appropriate method for handling missing data through statistical 
modeling, e.g., multiple imputation (MI) will be used. The estimand will provide an answer to 
the question that is crucial to individual subjects, “If I take this study medication as part of my 
treatment regimen, without adding any further medications that may impact the underlying 
disease or exit the study prematurely, what improvements in histology and PRO symptoms might 
be anticipated after 24 weeks?” 
5. 
Study Design 
5.1 
Study Overview 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the efficacy and safety of AK002 in patients with moderately to severely active EoD without EG 
who have an inadequate response with, lost response to, or were intolerant to standard therapies. 
Patients enrolled in the study will receive 6 infusions of placebo or AK002 administered every 
4 weeks and will be followed for 12 weeks after last dose unless patients elect to enter the 
optional open-label extension (OLE) period of the study.  
Patients will be consented and then screened for 21–45 days prior to Day 1. Patients who meet 
all eligibility criteria can be enrolled into the study. Patients 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. Patients rescreened within 30 days of signing 
the initial consent will not need to sign a new informed consent form (ICF) if no changes have 
been made to the ICF. 
Patients will undergo EGD and colonoscopy with biopsy at screening and again 4 weeks after 
last dose. The EGD and colonoscopy should take place on the same day in order to minimize 
effects of procedure premedication on the PRO scores. For patients with a history of EoE and/or 
with a score of ≥3 on the dysphagia question on at least 1 day during screening, esophageal 


 
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biopsies will also be collected at screening and postdose. Biopsies from the gastric mucosa, 
duodenum, colon, and esophagus (as applicable) will be taken and reviewed by a central 
pathology reader. Additional biopsies will be collected for exploratory analysis. 
The study is designed as follows: 
• 
A screening period of 21–45 days with baseline evaluations for study eligibility, including 
active symptoms of disease (gathered by the patient reported outcome [PRO] questionnaire 
completed during screening) and EGD and colonoscopy (performed on the same day) with 
biopsy. 
• 
Stool antigen test for Helicobacter pylori (H. pylori) will be assessed during screening to 
confirm no active H. pylori infection exists. If H. pylori is detected in tissue biopsies by the 
central pathologist, the patient should be excluded from the study. 
• 
Prior EGD and colonoscopy biopsy samples may be used for eligibility as long as they were 
performed within 45 days of the screening window for the AK002-021 study and were 
performed and centrally assessed using the same criteria as for the AK002-021 study.  
• 
If patients meet histology and symptom eligibility criteria, they will be randomized and 
stratified by the highest weekly mean TSS of disease activity recorded during the screening 
period (<28 or ≥28 strata). The IRT will assign patients 1:1 to receive 6 doses of AK002 or 
placebo. 
• 
Pre-study medications and dietary restrictions should remain unchanged throughout the 
screening period and throughout the study. Systemic or topical corticosteroids above 10 mg 
prednisone daily (or the equivalent thereof) will not be allowed, except as a premedication 
prior to the first infusion only, to treat an IRR that occurs during infusion, or the use is due 
to unforeseen circumstances when it is deemed medically necessary to treat an unrelated 
medical condition. 
• 
Eligible patients will receive the first dose of placebo or AK002 (3 mg/kg) on Day 1 with 
premedication of 80 mg oral prednisone 12–24 hours prior to the start of the infusion.  
• 
If the study drug is well tolerated (no stopping rules being met), patients will receive 
additional doses of placebo or AK002 (3 mg/kg) on Days 29, 57, 85, 113, and 141. With the 
exception of Day 1, steroid premedication will only be allowed with the written approval of 
the Medical Monitor.  
• 
Patients will remain at the site for at least 1 hour of observation following the end of the 
infusion.  


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
A ll a k os I nc. 
Pa ge 4 1 of 1 4 0 
C o nfi de nti al  
•  
A r e peat E G D a n d c ol o n osc o p y wit h bi o ps y will be perf or me d o n Da y 1 6 9 ( ± 3) or 
2 8 ( ± 3) da ys after last d ose of st u d y dr u g if patie nt earl y-ter mi nates fr o m t he st u d y 
(bet wee n t he Da y 2 9 visit a n d t he Da y 1 6 9 visit ). 
•  
Dail y a d mi nistr ati o n of t he P R O q uesti o n naire (i ncl u di n g a d diti o nal q uesti o ns) t hr o u g h o ut 
t he st u d y a n d t he f oll o w-u p peri o d f or all patie nts. 
•  
Patie nts will r ate t heir i m pr essi o n of disease se verit y  
 a n d disease i m pr o ve me nt 
 at s pecifie d ti me p oi nts d uri n g t he st u d y.  
•  
Patie nts 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 d ys p ha gia a n d c o nsti pati o n 
o n a dail y basis d uri n g scr ee ni n g a n d t hr o u g h o ut t he st u d y. T hese will be c o m plete d 
f oll o wi n g t he P R O q uesti o n nair e. 
•  
F oll o w- u p will occ ur f or 8 4 ( ± 3) da ys after last d ose of st u d y dr u g u n less patie nts deci de t o 
e nter t he l o n g -ter m, o pe n-la bel e xte nsi o n ( O L E) peri o d of t he st u d y. F oll o w-u p visits f or 
patie nts o pti n g n ot t o e nter t he O L E peri o d of t he st u d y will occ ur o n Da y 1 7 6 ( ± 3), Da y 
1 9 7 ( ± 3), a n d Da y 2 2 5 ( ± 3).  
•  
Patie nts w h o r ecei ve all  6 d oses of st u d y dr u g ha ve t he o pti o n t o recei ve A K 0 0 2 b y e nteri n g 
i nt o t he O L E peri o d of t he st u d y if all eli gi bilit y criteria f or t he O L E peri o d are satisfie d. 
Patie nts w h o e nter i nt o t he O L E peri o d of t he st u d y ma y  be gi n t he e xte nsi o n d osi n g 1 da y  
after c o m pleti n g t he Da y 1 7 6 visit of t his pr ot oc ol. O pe n-la bel e xte nsi o n patie nts will n ot 
c o m plete t he Da y 1 9 7 or Da y 2 2 5 pr oce d ures u n der t he d o u ble -bli n d peri o d of t he st u d y.  
•  
Eli gi ble patie nts w h o c h o ose t o partici 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 Assess me nts  (T a ble  8 i n A p pe n di x 1 3 ) after c o m pleti n g t he Da y 1 7 6 
d o u ble- bli n d peri o d pr oce d ur es a n d will recei ve t he first d ose of o pe n -la bel A K 0 0 2 
a p pr o xi matel y 1  wee k after Da y 1 6 9 ( o n Da y 1 7 7 ). 
•  
T otal st u d y d ur ati o n is a p pr o xi matel y 3 5 – 3 7 wee ks. F or patie nts e nteri n g i nt o t he O L E 
peri o d of t he st u d y, t he t otal st u d y d urati o n will be a p pr o xi matel y a n a d diti o nal 
2 8- 3 0 wee ks.  
5. 2  
S c he d ule of E ve nts 
T he o ver all sc he d ule of pr oce d ur es a n d assess me nts are descri be d i n  T a ble  2. 
 
 
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Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 4 2 of 1 4 0 
C o nfi de nti al  
T a ble  2  
St u d y A K 0 0 2-0 2 1 S c he d ule of Assess me nts : D o u ble-Bli n d P eri o d  
Ass ess me nt  Descri pti o n  
Scree ni n g  
( 2 1– 4 5 da ys)  
T re at m e nt Peri o d  
( 2 0 wee ks) 
F oll o w -U p Peri o d 3 0 
( 1 2 wee ks) 
 
B aseli ne 1 
 
Pri or t o  
D a y 1 
 
D ose 1  
D a y 1 2 
 
D a y 8 
( ± 2 d a ys) 
D a y 1 5  
( ± 2 d a ys) 
D ose 2  
D a y 2 9 
( ± 3 d a ys) 
D ose 3  
D a y 5 7 
( ± 3 d a ys) 
D ose 4  
D a y 8 5 
( ± 3 d a ys) 
D ose 5  
D a y 1 1 3 
( ± 3 d a ys) 
D ose 6  
D a y 1 4 1 
( ± 3 d a ys) 
D a y 1 6 9 
( ± 3 d a ys) 
or 2 8  d a ys 
after last 
d ose if E T 
D a y 1 7 6  
( ± 3 d a ys) 
or 3 5 d a ys 
after last 
d ose if E T 2 9 
D a y 1 9 7 
( ± 3 d a ys) 
or 5 6  d a ys 
after last d ose 
if E T2 9 
D a y 2 2 5 
( ± 3 d a ys) 
or 8 4  d a ys  
after last 
d ose if E T 
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p hics 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
M e dical Hist or y  
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Pri or a n d C o nc o mita nt Me dicati o ns  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
B o d y wei g ht a n d hei g ht 2 
X 
 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Vital Si g ns 3 
X  
 
X  
 
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
1 0 or 1 2- lea d E C G4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o m plete P h ysical E xa m 5 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
S y m pt o m- Directe d P h ysical E xa m 6 
 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
B as eli ne Diet Assess me nt 7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
B as eli ne Diet C o m plia nce 8 
 
 
X  
 
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
Pre vi o us Treat me nts a n d Pr oce d ure 
R e vie w  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
St o ol f or O va a n d Parasite 9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
St o ol a nti ge n test f or H. pyl ori 3 2 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
e P R O Acti vati o n a n d Trai ni n g 1 0 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
e P R O Q uesti o n naire ( will i ncl u de 
A d diti o nal Q uesti o ns) 1 1 
< ------------------------------------------------------------------ C o m plete electr o nicall y 1 ti me dail y ----------------------------------------------------------------> 
 
X 
 
X  
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
 
< ------------------------ C o m plete electr o nicall y o n Scree ni n g Da y 1 9, St u d y Da y 7, St u d y Da y 2 8, a n d St u d y Da y 2 2 5 or E T ----------------------------> 
 
< ---------------------------------- C o m plete electr o nicall y o n St u d y Da y 7, St u d y Da y 2 8 a n d St u d y Da y 2 2 5 or E T ----------------------------------------->  
E G D + c ol o n osc o p y wit h 
Bi o ps y 1 2, 1 4 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
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Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 43 of 140 
Confidential 
Table 2 
Study AK002-021 Schedule of Assessments: Double-Blind Period cont. 
Assessment Description 
Screening 
(21–45 days) 
Treatment Period 
(20 weeks) 
Follow-Up Period30 
(12 weeks) 
 
Baseline1 
 
Prior to 
Day 1 
 
Dose 1 
Day 12 
 
Day 8 
(±2 days) 
Day 15  
(±2 days) 
Dose 2 
Day 29 
(±3 days) 
Dose 3 
Day 57 
(±3 days) 
Dose 4 
Day 85 
(±3 days) 
Dose 5 
Day 113 
(±3 days) 
Dose 6 
Day 141 
(±3 days) 
Day 169 
(±3 days) 
or 28 days 
after last 
dose if ET 
Day 176 
(±3 days) 
or 35 days 
after last 
dose if ET29 
Day 197 
(±3 days) 
or 56 days 
after last dose 
if ET29 
Day 225 
(±3 days) 
or 84 days 
after last 
dose if ET 
Blood for CBC with differential21 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Chemistry15,22 
(Screening Chemistry includes 
hCG and FSH) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Serology and 
Strongyloides stercoralis 16 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for Total Serum IgE17 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Blood for PK23 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for ADA24 
X 
 
X 
 
 
X 
X 
X 
 
 
X 
 
 
X 
Urine for Urinalysis25 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
X25 
Dipstick Pregnancy Test26 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Eligibility Assessment 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Premedication: Prednisone19 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Access IRT: Stratification and 
Randomization18 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Access IRT: IP Kit Assignment 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Study Drug Administration20 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Non-serious Adverse Events27 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events28 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Begin OLE period of the study at 
least 1 day after Day 176 Visit 
(if applicable)29, 31 
 
 
 
 
 
 
 
 
 
 
 
X 
Day 197 and 
Day 225 visits are 
not applicable for 
OLE patients 
 


Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 4 4 of 1 4 0 
C o nfi de nti al  
T a bl e 2  N otes 
A D A:  
A nti -A K 0 0 2 a nti b o d y  
E T:  
E arl y T er mi nati o n  
I R T: 
I nt era cti ve Res p o nse T ec h n ol o g y 
C B C: 
C o m pl et e bl o o d c o u nt  
F S H:  
F ollicle -sti m ul ati n g h or m o ne 
 
  
E C G:   
El ectr ocar di o gra m 
h C G: 
H u m a n C h ori o ni c G o na d otr o pi n  
 
 
e P R O: el ectr o nic Pati e nt Re p ort e d O ut c o m e  
I P: 
I n vesti gati o nal Pr o d uct 
P K:  
P har ma c o ki neti cs  
1) 
Baseli ne scree ni n g visit ca n occ ur o ver se veral da ys wit hi n t he scree ni n g peri o d. Da y 1 ca n be gi n as s o o n as eli gi bilit y crit eri a are met.  
2) 
At scre e ni n g, hei g ht (i n c m) a n d wei g ht (i n k g) will be re c or de d. B o d y wei g ht will als o be m eas ure d o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, 1 4 1, a n d o n f oll o w -u p Da y s 1 7 6 , 1 9 7 a n d 2 2 5 
or 2 8 , 5 6, a n d 8 4 da ys aft er l ast d ose, if E T. C urre nt b o d y wei g ht or b o d y wei g ht fr o m 1 da y pri or will be use d t o cal c ulate t he a m o u nt of A K 0 0 2/ pla ce b o t o be mi xe d wit h 
Na Cl f or t he a p pr o priate d ose t o be a d mi nistere d o n e ac h i nf usi o n da y.  
3) 
Vit al si g ns will be m eas ure d at scre e ni n g, Da ys 1 7 6, 1 9 7, a n d 2 2 5 or 2 8 ,5 6 a n d 8 4 da ys after l ast d ose if E T a n d o n all d osi n g da ys: wit hi n 3 0 mi n ut es pre d ose, 
1 5 ( ± 5) mi n ut es aft er t he st art of st u d y dr u g i nf usi o n, wit hi n 1 5 mi n ut es f oll o wi n g t he e n d of i nf usi o n a n d j ust pri or t o disc har ge. A d diti o nal vit al si g ns m eas ure m e nts m a y be 
c oll ect e d at t he I n vesti gat or’s discreti o n if a n I R R occ urs. Vit al si g ns i ncl u di n g s yst olic a n d diast olic bl o o d press ure, p ulse, b o d y te m perat ure, a n d res pirat or y rat e will be 
m eas ur e d after t he patie nt has be e n at rest f or ≥5 mi n ut es a n d bef ore a n y bl o o d dra ws ha ve be e n o bt ai ne d ( u nl ess c olle ct e d f or a n I R R). 
4) 
A 1 0 -le a d or 1 2-l ea d E C G will be o bt ai ne d at scre e ni n g bef ore a n y bl o o d is dra w n a n d after t he pati e nt has be e n i n t he a p pro priate p ositi o n f or ≥5 mi n utes.  
5) 
A c o m plete p h ysic al e xa mi nati o n will be perf or m e d b y eit her t he I n vesti gat or or desi g ne e a n d i ncl u de t he f oll o wi n g b o d y s yst e m or or ga n assess m e nts: s ki n; he a d, e yes, ears, 
n ose a n d t hr oat; t h yr oi d; l u n gs; car di o vasc ular ; a b d o m e n; e xtre miti es; l y m p h n o des; a n d a brief ne ur ol o gi cal e xa mi nati o n. 
6) 
A s y m pt o m -dire ct e d p h ysi cal e xa m (i ncl u di n g assess me nt of p ossi bl e i nf usi o n site rea cti o ns) will be perf or m e d b y t he I n vesti gat or or desi g ne e, as nee de d, if a n y s y m pt o ms 
are re p orte d. 
7) 
A baseli ne diet assess me nt (A p pe n di x 3 ) will be perf or me d usi n g sta n dar diz e d q uesti o ns. E ati n g patter ns, f o o d a v oi da nc e be ha vi ors, a n d c o nfir m e d aller gi es will be ca pt ure d. 
8) 
A baseli ne diet c o m plia nce c hec k will be perf or m e d at e ver y st u d y visit, e xc e pt as n ote d a b o ve, a n d a n y varia nces fr o m t he baseli ne di et d oc u m e nte d. Patie nts s h o ul d m ai ntai n 
t he baseli ne diet t hr o u g h o ut t he st u d y. 
9) 
Fe c al c oll ecti o n kits f or o va a n d parasit e  test will be pr o vi de d t o patie nts at scree ni n g. C olle cti o n kits s h o ul d be ret ur ne d t o t he cli nic al site wit hi n 1 da y of c oll ecti o n. Ne gati ve 
res ults m ust be a vail a bl e pri or t o ra n d o mi zati o n. 
1 0) Acti vate P R O q uesti o n naire a n d pr o vi de patie nt wit h u ni q ue user na m e a n d pass w or d. P R O q uesti o n naire s h o ul d be acti vat e d f or all patie nts o n scre e ni n g Da y 1.  
1 1) P R O s h o ul d be c o m plete d ar o u n d t he sa m e ti me e ac h da y. Pri or t o e nr oll m e nt, t he P R O we e kl y a vera ges of a b d o mi nal pai n, na usea, a n d diarr he a o ver t he scre e ni n g peri o d 
will be c alc ul at e d a n d u se d t o assess eli gi bilit y. We e kl y a vera ge T ot al S y m pt o m Sc ore ( T S S 6) will be calc ul ate d f or eli gi bilit y a n d stratific ati o n. Pati e nts will als o c o m plete a n 
a d diti o nal q uesti o n e ac h a b o ut d ys p ha gia a n d c o nsti pati o n dail y 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. T he a d diti o nal q uesti o ns will be c o m pl et e d f oll o wi n g 
t he P R O q uesti o n naire.  
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Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 4 5 of 1 4 0 
C o nfi de nti al  
T a bl e 2  N otes c o nt. 
1 2) E G D + c ol o n osc o p y wit h bi o ps y ( perf or me d o n t he sa m e da y w he ne ver p ossi ble ) will i ncl u de s pe ci me ns fr o m t he gastric m uc osa, d u o de n u m, c ol o n a n d es o p ha g us (as 
a p pli ca ble). S pe ci me ns will be pr ocesse d b y t he c e ntral l a b orat or y. Se e t he Hist ol o g y Ma n ual f or c oll ecti o n , pr ocessi n g, a n d s hi p pi n g details. T he s pe ci me ns will be e val uate d 
b y a c e ntral pat h ol o g y re a der. A d diti o nal bi o psi es will be c oll e ct e d f or e x pl orat or y a nal ysis.  Pri or E G D a n d c ol o n osc o p y bi o ps y sa m pl es ma y be use d f or eli gi bilit y as l o n g as 
t he y were perf or me d wit hi n 4 5 da ys of t he A K 0 0 2-0 2 1 scre e ni n g wi n d o w f or t he A K 0 0 2 -0 2 1 st u d y a n d were perf or me d a n d c e ntrall y assesse d usi n g t he sa m e criteria as f or 
t he A K 0 0 2 -0 2 1 st u d y , a n d t here were n o c ha n ges t o E o D t hera p y f oll o wi n g t he E G D.  
1 3) T he 
 is to be c o m pl et e d ele ctr o nic all y b y patie nt, i n cli ni c, pri or t o a n y bl o o d dra w, p h ysi c al e xa m, or vital si g n m eas ure m e nts.  
1 4) Se e A p pe n di x 5  f or bi o ps y assess m e nts. T he p ost-treat m e nt E G D + c ol o n osc o p y a n d bi o ps y asse ss m e nts will be perf or me d o n Da y 1 6 9 ( ± 3) or 2 8 ( ± 3) da ys aft er last d ose of 
st u d y dr u g if E T. P ost-treat m e nt E G D + c ol o n osc o p y bi o ps y res ults will be bli n de d t o t he sit e.  
1 5) Bl o o d f or baseli ne c he mistr y, i ncl u di n g h C G a n d F S H, will be c oll ecte d d uri n g t he scre e ni n g peri o d. O nl y pati e nts of c hil d beari n g p ote nti al a n d p ost -m e n o pa usal w o me n are 
re q uire d t o ha ve h C G a n d F S H t esti n g c o m pl et e d.  
1 6) Bl o o d f or ser ol o g y testi n g will be c oll ecte d d uri n g scree ni n g a n d will i ncl u de H Bs A g, he patitis C a nti b o d y, a nti -H Bc, a n d HI V, as well as Str o n g yl oi des st erc oralis .  
1 7) Bl o o d sa m ples f or t otal ser u m I g E will be c olle ct e d d uri n g scre e ni n g a n d o n Da y 1 7 6 or 3 5 ( ± 3) da ys aft er last d ose of st u d y dr u g, if E T.  
1 8) Stratific ati o n base d o n T S S of < 2 8 or ≥2 8 will occ ur. Ra n d o miz ati o n a n d stratifi cati o n will be c o n d ucte d t hr o u g h t he I R T s yst e m.  
1 9) Pre me dic ati o n wit h 8 0 m g oral pre d nis o ne or a p pr o ve d alter nati ve is re q uire d 1 2 – 2 4 h o urs pri or t o t he first i nf usi o n. Pre m e di cati o n pri or t o t he start of t he se c o n d t hr o u g h 
si xt h i nf usi o ns will o nl y be a d mi nistere d wit h t he pri or writte n a p pr o val of t he Me di cal M o nit or. 
2 0) St u d y dr u g will be a d mi nistere d as a si n gl e peri p heral i ntra ve n o us i nf usi o n o ver at l east 4 h o urs f or D ose 1 a n d at l east 1 h o ur f or s u bse q ue nt d oses. R efer t o t he P har ma c y 
Ma n ual. 
2 1) Bl o o d f or C B C wit h differe nti al, i ncl u di n g a bs ol ute bl o o d e osi n o p hil c o u nt, will be o bt ai ne d o nc e d uri n g scre e ni n g , Da y 8, Da y 1 5 , a n d o nce d uri n g e ac h f oll o w -u p visit or 
E T visit, as well as t wice d uri n g d osi n g da ys j ust pri or t o ea c h i nf usi o n a n d 1 h o ur ( ± 1 5 mi n utes) after t he e n d of e ac h i nf usi o n . 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 he patie nt’s parti ci pati o n will be bli n de d t o t he S p o ns or a n d t he sit e. A n u nsc he d ul e d C B C m a y be c oll ecte d at t h e re q uest of t he Safet y 
M o nit or.  
2 2) Bl o o d f or c he mistr y will be o bt ai ne d o nce d uri n g scre e ni n g a n d o nc e d uri n g ea c h f oll o w -u p  visit  or E T visit as well as pre d ose o n d osi n g d a ys. 
2 3) Bl o o d f or P K will be o bt ai ne d pre d ose o n d osi n g Da ys 2 9, 5 7, 8 5, 1 1 3, a n d 1 4 1, as well as d uri n g scree ni n g a n d o n Da ys 8, 1 5, 1 6 9, 1 7 6, 1 9 7, a n d 2 2 5 or 2 8, 3 5, 5 6, a n d 
8 4 ( ± 3) da ys after last d ose of st u d y dr u g if E T. 
2 4) Bl o o d f or A D A will be c oll ecte d at scre e ni n g a n d pre d ose o n d osi n g Da ys 1, 2 9, 5 7, a n d 8 5, as well as o n Da y s 1 6 9 a n d 2 2 5 or 2 8 a n d 8 4 ( ± 3) da ys aft er last d ose of st u d y 
dr u g if  E T. T he A D A sa m ple will als o be c olle ct e d a n y ti me a n i m m u n o ge ni cit y -relate d A E occ urs. 
2 5) Uri ne f or st a n dar d uri nal ysis will be o bt ai ne d at scree ni n g, pre d ose o n d osi n g Da y 2 9, E T, a n d s y m pt o m base d, as ne cessar y.  
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Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 46 of 140 
Confidential 
Table 2 Notes cont. 
26) Urine will be collected for dipstick pregnancy test on all infusion days and on Day 176 and Day 197 or 35 and 56 (±3) days after last dose of study drug, for all patients of 
childbearing potential. Test kits will be supplied by the central laboratory. Tests will be completed on site and evaluated prior to each infusion. 
27) The capture of non-serious AE and AESI will begin after the first dose of study drug has occurred. 
28) The reporting of SAE occurring after signing the informed consent and prior to the first infusion 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 infusion of study drug. For patients participating in the OLE period, AE will be assessed 
and recorded in the CRF of the AK002-021 double-blind treatment period database up until the start of the first open-label infusion, after the Day 176 visit. The AE will be 
recorded in the CRF of the AK002-021 OLE period database beginning with the start of the first open-label infusion after Day 176. 
29) Patients who continue in the OLE period of the study will complete the procedures for Day 176 and may begin open-label dosing in the OLE period of the study, if eligible, 
1 day after completion of the Day 176 visit. In this case, patients will not complete the Day 197 or Day 225 procedures under the double-blind period of the study.  
30) The ET visits should be conducted 28, 35, 56, and 84 (±3) days after last dose of study drug or prior to this, if necessary, to ensure compliance with the visit. If only 1 ET visit 
is possible, EGD + colonoscopy and end-of-study procedures may occur on the same day. If the end-of-study visit occurs more than 35 days after last dose of study drug, then 
perform the visit as soon as possible. The procedures listed under the 28-day and 35-day post-study drug visit will be conducted unless otherwise directed by the Medical 
Monitor. For patients participating in the OLE period, AE and concomitant medications should be collected and recorded in the AK002-021 double-blind treatment period 
database up until the start of the first open-label infusion after the Day 176 visit. This includes prednisone premedication administered after the Day 176 visit of the OLE 
period, which should be recorded in the Concomitant Medications CRF of both the AK002-021 double-blind treatment period database and the AK002-021 OLE period 
database. 
31) The final hematology assessment for the double-blind period of the study must be collected prior to the patient taking prednisone premedication for the first dose of the OLE 
period. Therefore, dosing in OLE must take place at least 1 day after completion of the Day 176.  
32) Stool antigen test for H. pylori will be obtained to confirm that no existing active H. pylori infection is present. Fecal collection kits (same container as for ova and parasite 
testing) should be returned to the clinical site within 1 day of collection. Negative results must be available prior to randomization. If H. pylori is detected in tissue biopsies by 
the central pathologist, the patient should be excluded from the study. In case of a positive test, the patient must be screen-failed. After H. pylori treatment and an additional 
6 weeks later, patient may be reconsented and will receive a new patient number. 
 
 


 
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Page 47 of 140 
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6. 
Criteria for Evaluation 
6.1 
Safety Endpoints 
The safety and tolerability of AK002 will be assessed by determining the following:  
• 
Adverse events (Section 13.1) including severity, withdrawals due to AE, and other safety 
parameters 
• 
Adverse events of special interest (AESI), IRR, malignancy, and opportunistic infections 
(Section 13.3) 
• 
Anti-drug antibodies (Section 11.5.4): Blood (serum) will be collected for assessment of 
ADA using a validated assay method. The ADA blood samples will be obtained at 
screening, predose on Days 1, 29, 57, 85, and additionally on Day 169 and Day 225 or 
84 (±3) days after last dose, if ET.  
• 
Blood chemistry (Section 11.5) 
• 
Hematology (Section 11.2.5) 
• 
Urinalysis (Section 11.5.2) 
• 
Physical examination (Section 11.3.2 and Section 11.3.5) 
• 
Changes in vital signs (Section 11.3.7) 
• 
Changes in concomitant medication use due to AE (Section 11.3.1) 
6.2 
Pharmacokinetic Endpoints  
Blood (serum) will be collected for assessment of AK002 concentrations using a validated 
enzyme-linked immunosorbent assay (ELISA) method.  
Pharmacokinetic (PK) blood samples will be obtained at screening, predose on Days 29, 57, 85, 
113, and 141 and additionally on Days 8, 15, 169, 176, 197, and 225 or 28, 35, 56, and 84 (±3) 
days after last dose, if ET. AK002 concentrations in serum will be used to calculate AK002 
exposure. 
6.2.1 
Primary Efficacy Endpoints 
To evaluate the efficacy and safety of 6 doses of AK002 in patients with moderate to severe EoD 
when compared with placebo. Efficacy will be evaluated by the following co-primary endpoints:  
1) 
Proportion of tissue eosinophil responders at Week 24. A responder is a patient achieving a 
mean duodenal eosinophil count ≤15 cells/hpf in 3 highest duodenal hpf. 
2) 
Change in TSS from baseline to Weeks 23–24 as measured by the PRO questionnaire. 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 4 8 of 1 4 0 
C o nfi de nti al  
T he P R O T S S is c o m prised of  6 s y m pt o ms, as liste d bel o w:  
•  
A b d o mi nal pai n i nte nsit y  
•  
Na usea i nte nsit y  
•  
F ull ness bef or e meal i nte nsit y  
•  
L oss of a p petite i nte nsit y  
•  
Bl oati n g i nte nsit y  
•  
A b d o mi nal cr a m pi n g i nte nsit y  
T he se verit y a n d fr e q ue nc y of diarr hea a n d v o miti n g will als o be c ollecte d o n t he P R O 
q uesti o n nair e b ut will n ot be i ncl u de d i n t he calc ulati o n of t he T S S.  
6. 2. 2  
Sec o n d ar y Effic ac y E n d p oi nts  
T o f urt her c har acterize t he efficac y of A K 0 0 2 i n patie nts wit h E o D as meas ure d b y:  
•  
C ha n ge i n tiss ue e osi n o p hils fr o m baseli ne t o Wee k 2 4. 
•  
Pr o p orti o n of patie nts ac hie vi n g  mea n  e osi n o p hil c o u nt ≤1  cell/ h pf i n 3 hi g hest d u o de nal 
h pf at Wee k 2 4. 
•  
Pr o p orti o n of tr eat me nt r es p o n ders  at Wee ks 2 3– 2 4. A r es p o n der is defi ne d as  > 3 0 % 
i m pr o ve me nt i n T S S  a n d mea n e osi n o p hil c o u nt ≤1 5 cells /h pf i n 3 hi g hest d u o de nal h pf.  
•  
Pr o p orti o n of patie nts w h o ac hie ve ≥5 0 % re d ucti o n i n T S S fr o m baseli ne t o Wee ks 2 3 – 2 4. 
•  
Pr o p orti o n of patie nts w h o ac hie ve ≥7 0 % re d ucti o n i n T S S fr o m baseli ne t o Wee ks 2 3 – 2 4. 
•  
C ha n ge i n wee kl y T S S o ver ti me.  
6. 2. 3  
E x pl or at or y Effic ac y E n d p oi nts  
T o e val uate t he eff ect of A K 0 0 2 b y c o m pari n g A K 0 0 2 t o place b o treat me nt f or t he f oll o wi n g 
par a meters:  
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me . 
•  
C ha n ges i n 
 fr o m baseli ne c o m pare d t o p ost-treat me nt i n t he  
 
 will be n ote d. 
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me . 
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me . 
C CI
C CI
C CI
C CI
C CI


 
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Date: 16 June 2022 
Allakos Inc. 
Page 49 of 140 
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7. 
Patient Selection 
7.1 
Number of Patients 
A total of approximately 80 patients will be dosed in the study in which 40 patients will receive 
6 doses of 3 mg/kg AK002 and 40 patients will receive 6 doses of placebo every 4 weeks in a 
randomized, double-blind manner. All patients will be pretreated with 80 mg prednisone the day 
before the first infusion. 
7.2 
Number of Sites 
Approximately 35 sites in the United States will participate in this study. 
7.3 
Study Population 
Approximately 80 male and female patients with moderately to severely active EoD (without 
EG), aged ≥18 and ≤80 years, who fulfill the eligibility criteria specified below, will be enrolled 
into the study.  
7.4 
Inclusion Criteria 
Patients are eligible to enroll in the study if all of the following criteria are met: 
1) 
Provide written informed consent. 
2) 
Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for 
entry. 
3) 
Baseline endoscopic biopsy with ≥30 eosinophils/hpf in at least 3 hpf in the duodenum as 
determined by central histology assessment of biopsies collected during the screening EGD 
without any other significant cause for the eosinophilia. 
4) 
Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks 
during screening. 
5) 
A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the PRO 
questionnaire (score from 0–10) for at least 2 weeks of screening and a weekly average TSS 
of ≥10 for at least 2 weeks of screening. 
6) 
Inadequate or loss of response to, or intolerant to standard therapies for EoD symptoms, 
which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, 
among others. 
7) 
If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions 
throughout the study. 
8) 
Willing and able to comply with all study procedures and visit schedule including 
follow-up visits. 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 50 of 140 
Confidential 
9) 
Female patients must be either post-menopausal for at least 1 year with FSH level 
>30 MIU/mL at screening or surgically sterile (tubal ligation, partial or total hysterectomy, 
or bilateral oophorectomy) for at least 3 months or, if of childbearing potential, have a 
negative pregnancy test and agree to use dual methods of contraception, have a partner who 
had a vasectomy, or agree to abstain from sexual activity from screening until the end of the 
study, or for 120 days following last dose of study drug, whichever is longer. 
 
Non-vasectomized male patients with female partners of childbearing potential must agree 
to either abstain from sexual activity or agree to use a highly effective method of 
contraception from screening until the end of the study or for 120 days following last dose 
of study drug, whichever is longer. All fertile men with female partners of childbearing 
potential should be instructed to contact the Investigator immediately if they suspect their 
partner might be pregnant (e.g., missed or later menstrual period) at any time during study 
participation. 
7.5 
Exclusion Criteria 
Patients will be excluded from the study if they meet any of the following criteria: 
1) 
Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day 
prednisone within 4 weeks prior to the screening visit. 
2) 
Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the gastric mucosa as 
determined by central histology assessment of biopsies collected during the screening EGD. 
3) 
Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet 
therapy within 4 weeks prior to the screening visit. 
4) 
Treatment with any immunosuppressive or immunomodulatory drugs that may interfere 
with the study within 12 weeks prior to the screening visit. 
5) 
Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug. 
6) 
Active H. pylori infection as confirmed by a stool antigen test for H. pylori. 
7) 
History of inflammatory bowel disease, other chronic inflammatory diseases in the colon 
(with the exception of eosinophilic colitis), celiac disease, achalasia, or esophageal surgery. 
8) 
History of bleeding disorders and/or esophageal varices considered to be significant by the 
Investigator. 
9) 
Other significant causes of gastric and/or duodenal eosinophilia or eosinophilic 
granulomatosis with polyangiitis (EGPA). 
10) Confirmed diagnosis of hypereosinophilic syndrome (HES). 


 
Protocol AK002-021 
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11) Women who are pregnant, breastfeeding, or planning to become pregnant while 
participating in the study. 
12) Presence of an abnormal laboratory value considered to be clinically significant by the 
Investigator. 
13) Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion 
of the Investigator, would place the patient at increased risk. 
14) History of malignancy, except carcinoma in situ, early-stage prostate cancer, or 
non-melanoma skin cancers. However, patients with cancers that have been in remission for 
more than 5 years and are considered cured can be enrolled. 
15) Treatment for a clinically significant helminthic parasitic infection within 6 months of 
screening. 
16) Positive helminthic infection on ova and parasite (O&P) test.  
17) Seropositive for Strongyloides stercoralis at screening. 
18) Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients 
with past but resolved hepatitis, at screening. See Appendix 12. 
19) Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment 
in the study, during the treatment period, or vaccination expected within 5 half-lives 
(4 months) of study drug administration. This exclusion criterion does not apply to all types 
and formulations of vaccines authorized by FDA or other regulatory authority for the 
prevention of COVID-19, which may be administered before, during, or after the study. 
The vaccine should not be administered within 7 days before and within 7 days after the 
administration of AK002 so that any side effects caused by either of the 2 medications can 
be more easily determined. 
20) Participation in a concurrent interventional study with the last intervention occurring within 
30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, 
for biologic products). 
21) Known history of alcohol, drug, or other substance abuse or dependence that is considered 
by the Investigator to be ongoing and clinically significant. 
22) Any other reason that in the opinion of the Investigator or the Medical Monitor makes the 
patient unsuitable for enrollment. 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 5 2 of 1 4 0 
C o nfi de nti al  
7. 6  
S af et y E v al u ati o ns  
Saf et y a n d t oler a 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 c o m plicati o ns r es ulti n g fr o m t he i ntra ve n o us i nf usi o n. All T E A E will be c ollecte d 
fr o m t he start of st u d y dr u g a d mi nistr ati o n i n t he 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 
start of st u d y dr u g a d mi nistr ati o n i n t he O L E peri o d of t he st u d y, Da y 2 2 5, if patie nt is n ot 
e nr olli n g i n t he O L E peri o d of t he st u d y, or 8 4 da ys after last d ose, if E T. 
Se verit y will be assesse d usi n g t he Nati o nal Ca ncer I ns tit ute ( N CI) C o m m o n T er mi n ol o g y 
Criteria f or A d verse E ve nts ( C T C A E), versi o n 5. 0 or m ost c urre nt versi o n. All A E will be 
assi g ne d a se verit y gr a de a n d will be assess e d f or cli nical si g nifica nce a n d relati o ns hi p t o st u d y 
dr u g. A d verse e ve nts of s pecial i nter est will be n ote d.  
A d diti o nal saf et y e val uati 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 A K 0 0 2, C B C, 
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 r e vie w bli n de d safet y data t hr o u g h o ut t he s t u d y. Certai n safet y data 
( p ost-tr eat me nt cell diff er e ntials, as well as tiss ue e osi n o p hil a n d 
) 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 he desi g nate d Safet y M o nit or 
will r e vie w bli n de d saf et y data as we ll as p ost- treat me nt cell c o u nts a n d will escalate t o t he 
Me dical M o nit or as nee de d  i n a ma n ner t hat d oes n ot ca use bias.  
A n i n de pe n de nt Data M o nit ori n g C o m mittee (i D M C) has bee n c o n ve ne d a n d will meet at 
r e g ularl y sc he d ule d i nter vals i n acc or da nce wit h t he i D M C c harter.  
8.  
P ri 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 me dicati o ns i ncl u de b ot h prescri be d a n d o ver -t he-c o u nter me dicati o ns a n d 
will be r ec or de d i n t he electr o nic Case Re p ort F or ms (e C R F) f or 3 0 da ys pri or t o t he scree ni n g 
visit. Pri or me dicati o ns use d f or t he tr eat me nt of E o D s y m pt o ms, e ve n if t he y are > 3 0  da ys 
bef or e t he scr ee ni n g visit, will be d oc u me nte d i n t he e C R F.  
F or patie nts partici pati n g i n t he O L E peri o d, c o nc 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 2 1 d o u ble - bli n d tr eat me nt peri o d data base 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 he d o u ble- bli n d peri o d of t he st u d y  u p u ntil t he first o pe n -la bel d ose is 
a d mi nister e d after t he Da y 1 7 6 visit. T his i ncl u des t he pre d nis o ne pre me dicati o n a d mi nistere d 
after t he Da y 1 7 6 visit i n t he O L E peri o d, w hic h s h o ul d be rec or de d i n t he C o nc o mita nt 
Me dicati o ns C R F of b ot h t he A K 0 0 2 -0 2 1 d o u ble -bli n d treat me nt peri o d data base a n d t he 
A K 0 0 2 -0 2 1 O L E peri o d data base.  
C CI


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 53 of 140 
Confidential 
Any medications should have been stopped as required in the exclusion criteria. Patients should 
be advised against taking any new medication, both prescribed and over the counter, without 
consulting the Investigator, unless the new medication is required for emergency use or it is a 
vaccine to prevent COVID-19. Immediately prior to the first infusion, study site personnel 
should ensure that the patient continues to meet the inclusion criteria and none of the exclusion 
criteria (including no receipt or use of prohibited medications). 
All medications taken for the 30 days before screening and during participation in this study 
must be documented on the eCRF. All medications used to treat IRR or AE must be documented. 
All medications given as preparation for and during the conduct of the EGD and colonoscopy 
must also be documented.  
All AE, whether elicited by questions from study staff, volunteered, or noted on physical 
examination/laboratory testing, and regardless of causality or severity, will be assessed and 
recorded in the eCRF beginning after the first administration of study drug in the double-blind 
period of the study and ending at the time of study completion or early termination of the 
double-blind period or the OLE period, whichever is later.  
8.1 
Prohibited Medications  
Any biologics or other medications, such as systemic immunosuppressive or immunomodulatory 
drugs that may interfere with the study efficacy or safety assessments including but not limited to 
IL-5 modulators (e.g., benralizumab, reslizumab, mepolizumab), IL-4 and/or IL-13 antagonists 
(e.g., dupilumab), calcineurin inhibitors (e.g., cyclosporin, tacrolimus), mTOR inhibitors (e.g., 
sirolimus, everolimus), anti-metabolites (e.g., azathioprine, methotrexate, 6-mercaptopurine, 
leflunomide, mycophenolate mofetil), alkylating agents (e.g., cyclophosphamide), TNF 
inhibitors (e.g., infliximab, adalimumab), anti-IgE antibodies (e.g., omalizumab), JAK inhibitors, 
and eosinophil-depleting drugs (e.g., pramipexole).  
Patients will be reminded to not take prohibited medications and to notify the site immediately if 
a prohibited medication is prescribed by another health care provider. If a prohibited medication 
is started during the course of the study, the patient may be withdrawn from study treatment and 
followed for the 12-week follow-up period. The follow-up EGD may not be performed.  
Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the 
protocol, during the treatment period, or vaccination expected within 5 half-lives (4 months) of 
AK002 administration is prohibited.  
Prohibited medication(s) given within 24 hours of an infusion, if medically necessary for the 
treatment of an IRR, is acceptable and not considered a deviation from the protocol. 


 
Protocol AK002-021 
Amendment 2 
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Allakos Inc. 
Page 54 of 140 
Confidential 
8.2 
Restricted Medications 
The use of systemic corticosteroids given as pre-infusion prophylaxis or for the treatment of IRR 
is allowed and will not be considered a deviation from the protocol. The use of systemic or 
swallowed corticosteroids at a dose equivalent to >10 mg/day of prednisone for the treatment of 
EoD at any point in the study will be considered rescue therapy. However, the subject may 
remain in the study. The use of systemic or swallowed corticosteroids at a dose equivalent to 
>10 mg/day of prednisone is restricted and must be limited to cases of medical necessity when 
no other alternatives are available. The corticosteroids must be documented along with the 
reasons for use, and attempts should be made to discontinue the corticosteroids as early as 
possible. 
The use of PPI during the study is allowed provided that the subject is on a stable dose during the 
screening period and agrees to continue on the same dose through the end of the study. Initiation 
of PPI therapy or an increase in the dose of an oral PPI following the screening period will be 
considered a rescue therapy and will only be allowed if the Investigator deems such treatment to 
be medically necessary. In this case, discontinuation of the PPI therapy prior to Study Week 21 
should be considered if medically safe in the opinion of the Investigator. 
The use of sodium cromolyn for subjects who were on a stable dose during the screening period 
is allowed provided that they are willing to remain on the same dose of sodium cromolyn 
through the end of the study. Initiation or increase in the dose of sodium cromolyn following the 
screening period will be considered a rescue therapy and will only be allowed if the Investigator 
deems such treatment to be medically necessary. In this case, discontinuation of the sodium 
cromolyn therapy prior to Study Week 21 should be considered if medically safe in the opinion 
of the Investigator. 
8.3 
Allowed Medications  
Medications, other than those that are prohibited or restricted (Section 8.1 and Section 8.2), such 
as antihistamines, leukotriene antagonists, and sodium cromolyn are allowed during the study 
and, unless required due to unforeseen medical necessity, doses and/or dietary modifications are 
to remain stable. 
All types and formulations of vaccines approved by FDA or other regulatory authority for the 
prevention of COVID-19 may be administered before, during, or after the study. The vaccine 
should not be administered within 7 days before and within 7 days after the administration of 
study drug so that any side effects caused by either of the 2 medications can be more easily 
determined. 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 5 5 of 1 4 0 
C o nfi de nti al  
S yste mic or s wall o we d c ortic oster oi ds wit h a d ose of ≤1 0 m g/ da y pre d nis o ne or e q ui vale nt bei n g 
use d at t he ti me of st u d y e ntr y ar e acce pta ble as l o n g as t he d ose re mai ns sta ble t hr o u g h o ut 
scr ee ni n g a n d d uri n g t he st u d y.  
S h ort c o urses or a si n gle use of c ortic oster oi d t hera p y at d oses of ≤1 0 m g/ da y of pre d nis o ne or 
e q ui vale nt d ue t o u nf or esee n me dical necessit y f or c o n diti o ns ot her t ha n t he disease u n der st u d y 
will be all o we d at t he discr eti o n of t he I n vesti gat or pr o vi de d t hat t he c ortic oster oi ds are 
disc o nti n ue d pri or t o St u d y Wee k 2 1. C o nsi derati o n s h o ul d be gi ve n t o alter nati ve t hera pies 
w he ne ver p ossi ble.  
S wall o we d or s yste mic c ortic oster oi ds at a d ose of > 1 0 m g are n ot c o nsi dere d pr o hi bite d u n der 
t he f oll o wi n g cir c u msta nces: 
•  
S yste mic c ortic oster oi ds g i ve n wit hi n 2 4 h o urs of t he start of a n i nf usi o n w he n me dicall y 
necess ar y f or t he tr eat me nt of a n I R R.  
•  
A si n gle d ose of I V c ortic oster oi d gi ve n d uri n g t he E G D t o mi ni mize A E ass ociate d wit h  
a nest hesia ( e. g., na usea a n d v o miti n g after a nest hesia).  
•  
Pr e me dica ti o n wit h pr e d nis o ne pri or t o D ose 1 i n t he d o u ble-bli n d peri o d a n d D ose 1  i n t he 
O L E peri o d, as r e q uir e d b y t he  pr ot oc ol. 
•  
Pr e me dicati o n wit h a s yste mic c ortic oster oi d  (f or a n y d ose ot her t ha n D ose 1 i n t he 
d o u ble- bli n d peri o d a n d D ose  1 i n t he O L E peri o d), w hic h has bee n prea p pr o ve d b y t he 
Me dical M o nit or pri or t o d osi n g . 
All me dicati o n use d d uri n g t he scr ee 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 me dicati o ns t hat are ta ke n m ust re mai n sta ble t hr o u g h o ut t he st u d y.  
Me dicati o ns a d mi nister e d f or t he E G D a n d c ol o n osc o p y are all o we d. Me dicati o ns a d mi nistere d 
f or b o wel pr e par ati o n pri or t o c ol o n osc o pies are als o all o we d. 
All patie nts will be pr etr eate d wit h 8 0 m g pre d nis o ne t he da y bef ore t he first i nf usi o n.  
9.  
St u d y Tre at m e nt  
9. 1  
F or m ul ati o n of Test P r o d uct a n d Pl ace b o  
A K 0 0 2 is a h u ma nize d n o n -f uc os ylate d I g G 1 m o n ocl o nal a nti b o d y directe d a gai nst Si glec- 8. 
A K 0 0 2 dr u g pr o d uct is s u p plie d as a st erile li q ui d i n a si n gle -use 1 0 R glass vial wit h a fill 
v ol u me of n ot less t ha n 1 0 m L. T he pr o d uct is st ore d at 2° C t o 8° C. T he A K 0 0 2 f or m ulati o n is 
 
 p H 6. 0, i n sterile Water f or I njecti o n ( W FI).  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 5 6 of 1 4 0 
C o nfi de nti al  
Place b o is s u p plie d as a sterile li q ui d i n a si n gle -us e 1 0 R glass vial wit h a fill v ol u me of n ot less 
t ha n 1 0 m L. Place b o c o ntai ns 
 
 p H 6. 0, i n sterile WFI .  
N ote : A K 0 0 2 a n d place b o will be r ef erre d t o as “st u d y dr u g. ”  
9. 2  
St u d y Dr u g P ac k a gi n g a n d L a beli n g  
St u d y dr u g is s u p plie d as a sterile li q ui d i n a si n gle -use 1 0 R glass vial wit h a fill v ol u me of 
a p pr o xi matel y 1 0. 6 m L. Glass vials ar e pl u g ge d wit h T efl o n -c oate d r u b ber st o p pers a n d seale d 
wit h al u mi n u m seals.  
E ac h vial will be la bele d wit h t he r e q uire d 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 or a 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 oc u me nt Patie nt I D a n d pre parati o n date. T his tear -off la bel s h o ul d be 
a p plie d t o t he I P D ose Calc ulati o n a n d Pre parati o n W or ks heet a n d mai ntai ne d wit h t he s o urce 
d oc u me nts.  
9. 3  
S u p pl y of St u d y Dr u g t o t he I n vesti g ati o n al Site  
T he S p o ns or ( or desi g nee) will s hi p st u d y dr u g t o t he i n vesti gati o nal sites. T he i nitial st u d y dr u g 
s hi p me nt will be s hi p pe d after all r e q uire d re g ulat or y d oc u me ntati o n a n d a p pr o vals ha ve bee n 
r ecei ve d b y t he S p o ns or, t he c o ntr act has bee n e xec ute d, a n d t he first scree ne d patie nt is e ntere d 
i nt o t he I R T. 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 maticall y base d o n 
pr e deter mi ne d s u p pl y le vels a n d e nr oll me nt acti vit y at t he site.  
9. 4  
St u d y Dr u g D os a ge  a n d D os a ge Re gi me n  
Patie nts will be r a 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 6 d oses of 
3 m g/ k g A K 0 0 2 or place b o. T he e xact d ose will be calc ulate d pri or t o eac h i nf usi o n a n d base d 
o n c urr e nt patie nt wei g ht. St u d y dr u g will be a d mi nistere d as a si n gle peri p heral i ntra ve n o us 
i nf usi o n usi n g a n i nf usi o n p u m p as i n dicate d i n t he st u d y P har mac y Ma n ual o n Da ys 1, 2 9, 5 7, 
8 5, 1 1 3, a n d 1 4 1 ( ± 3).  
9. 5  
P re 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 pr e pare t he st u d y dr u g f or eac h i nf usi o n. Base d o n patie nt 
wei g ht o btai ne d t he da y of d osi n g, t he desi g nate d st u d y p har macist will pre pare t he a p pr o priate 
dil uti o n of A K 0 0 2 or place b o f or i ntr a ve n o u s a d mi nistrati o n.  
A p pr o priate ase ptic tec h ni q ue will be use d, a n d t he dr u g will be pre pare d acc or di n g t o t he 
P har mac y Ma n ual f or A K 0 0 2. Ref er  t o t he P har mac y Ma n ual f or a d diti o nal details a n d ste p- b y-
ste p i nstr ucti o ns r e gar di n g st u d y dr u g pre parati o n. Bas e d o n c urre nt U S P 2 0 1 9 g ui deli nes, 
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AK002 is not considered to be a hazardous drug, and therefore, special precautions do not need 
to be taken when handling or preparing the study drug.  
The infusion must be completed within 8 hours of preparation. Preparation is when 
AK002/placebo is first mixed with NaCl. 
9.6 
Study Drug Administration 
Specific instructions on administration and supplies required for administration are detailed in 
the Pharmacy Manual. In general, study drug will be infused through a peripheral vein IV set. 
The IV line will be kept open before and after the infusion with sufficient quantities of 
0.9% NaCl to assure patency.  
A volume of 100 mL* of the calculated dose of study drug will be infused over at least 4 hours 
on Study Day 1, over at least 1 hour on Study Days 29, 57, 85, 113, and 141 (±3). If the infusion 
is slowed or interrupted, the time may be extended longer than 4 hours, as long as it does not 
exceed 8 hours. 
* 
Due to rounding of the total infusion volume by some programmable infusion pumps, an 
infusion of 99 to 101 mL will be considered a complete infusion and will not be recorded as 
a deviation from the study. 
For the first infusion of study drug, patients will be premedicated with 80 mg oral prednisone (or 
approved equivalent) 12–24 hours prior to the start of the study drug infusion. For subsequent 
infusions, steroid premedication may be used at the discretion of the Investigator and with 
written approval from the Medical Monitor.  
The intravenous infusion may be interrupted, and/or the rate may be reduced if a patient has an 
IRR. The time the infusion is initiated/concluded (including any interruptions) will be 
documented in the eCRF. If the infusion is restarted after an interruption, the infusion must be 
completed within 8 hours of preparation. Administration will be discontinued if, in the opinion of 
the Investigator, an interrupted infusion cannot be restarted for safety reasons or if the infusion 
cannot be completed within 8 hours of preparation. Administration will also be discontinued in 
any patient experiencing a serious adverse event (SAE) during the course of the infusion.  
The initial infusion should be given over at least a 4-hour period, and the subsequent infusions 
should be given over at least a 1-hour period, depending on the patient’s tolerance of the 
previous infusions and at the Investigator’s discretion. Any reduction in the infusion rate 
schedule due to tolerability will not be considered a deviation from the protocol. All infusions 
must be completed within 8 hours of the study drug being mixed with NaCl. The patient will be 
observed for at least 1 hour after the end of each infusion as per the Investigator’s discretion.  


 
Protocol AK002-021 
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Date: 16 June 2022 
Allakos Inc. 
Page 58 of 140 
Confidential 
As treatment assignment during the double-blind, placebo-controlled part of the study will be 
masked, all eligible patients that choose to participate in the OLE period of the study will self-
administer 80 mg of oral prednisone premedication 12–24 hours prior to the first OLE infusion 
as well. 
9.7 
Study Drug Storage 
Study drug will be stored by the study sites at 2°C to 8ºC under lock at the designated pharmacy 
location. Access will be restricted to designated pharmacy staff. The 0.9% NaCl will be stored at 
ambient temperature, per manufacturer’s requirements. All study drug and NaCl will be stored in 
an area that is temperature controlled and monitored. If the temperature of study drug storage in 
the clinic/pharmacy exceeds or falls below this range, it will be quarantined and reported to the 
Sponsor or designee. The Sponsor will notify the site if the study drug is to be released from 
quarantined. 
9.8 
Study Drug Accountability 
The site’s study pharmacist/designee is responsible for maintaining accurate and current records 
accounting for the receipt, dispensing, preparation, use, return (or destruction), and final 
disposition of all investigational product (IP). All dosage calculations will be documented on the 
source documents. The Master IP Accountability Log should be used to capture receipt, 
dispensing, and return (or destruction). Electronic IP accountability systems may be used, 
depending on site preference, as long as the same information is captured. The study monitor 
will verify entries on these documents throughout the course of the study.  
Study drug will be labeled with kit numbers but will not reveal whether the kit contains active 
drug or placebo. 
10. Patient Numbering, Stratification, Randomization, and Blinding 
10.1 
Patient Numbering  
Each patient who provides informed consent will be assigned a patient identification number 
(PID) that uniquely identifies them as a patient in the study. The PID will consist of a 9-digit 
number: 
• 
The first 3 digits designate the study number. For this study, the number is 221. 
• 
The second 3 digits designate the site number. 
• 
The last 3 digits designate the order of consent at the site (the first patient who provides 
consent is 001, the second patient is 002, etc.). 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 59 of 140 
Confidential 
The patient will maintain the same PID throughout the study. If a patient signs the ICF but does 
not meet the inclusion/exclusion criteria or qualifies for the study but does not enroll, they may 
be assigned a new PID and rescreened once. Patients rescreened within 30 days of signing the 
initial consent will not need to sign a new ICF providing no changes have been made to the ICF. 
10.2 
Stratification and Randomization 
To be randomized into the study, a patient must have a weekly average score of ≥3 (on a scale 
from 0–10) recorded for either abdominal pain, nausea, and/or diarrhea on the PRO 
questionnaire for at least 2 weeks during screening and an average weekly TSS ≥10 for at least 
2 weeks during screening. Completion of at least 4 daily PRO questionnaires per week, for a 
minimum of 3 weeks during screening, is required to qualify. Patients will be randomized 
through the Interactive Response Technology (IRT) system. 
If the patient qualifies for the study after completing all of the screening procedures on the day 
prior to or on the day of the first infusion (Study Day 1), the site will access the IRT system in 
order to stratify and randomize the patient in the study and enter the current body weight for 
study drug dose calculation. The site will enter the highest weekly TSS of disease activity 
recorded during the screening period in order to stratify patients into screening TSS <28 or 
≥28 strata. The IRT system will then randomly assign the patient at a 1:1 allocation ratio to 
AK002 3 mg/kg for 6 doses, or placebo in a double-blind manner and will send an email to the 
pharmacist and/or designee detailing the kit number(s) to use to prepare the infusion.  
Approximately 40 patients will be randomized to treatment with AK002 at a dose of 3 mg/kg for 
6 doses, and approximately 40 patients will be randomized to placebo. A minimum number of 
approximately 80 patients with EoD without EG will be enrolled.  
A patient is considered enrolled in the study when the patient is randomized. 
For subsequent infusions on Days 29, 57, 85, 113, and 141, the coordinator will access the IRT 
on the day of infusion and enter the PID as well as the patient’s body weight, and the system will 
assign the patient the dose according to their randomization number. The pharmacist and/or 
designee will then receive an email detailing the kit number(s) to prepare, as well as the volume 
of study drug to be mixed with NaCl. 
Prior to each infusion, the Investigator or designee will confirm the PID recorded on the IV bag 
provided by the Pharmacist matches the patient. The patient identification should be confirmed 
and documented by a second party prior to administering the infusion, whenever possible. There 
will not be any unblinding information on the IRT notification to the Pharmacist or on the 
infusion bag provided to the site.  


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 6 0 of 1 4 0 
C o nfi de nti al  
T he assi g n me n t of tr eat me nt t o A K 0 0 2 or place b o will be sec urel y retai ne d i n t he I R T s yste m 
u ntil s uc h ti me as desi g nate d b y t he Statistical A nal ysis Pla n.  
1 0. 3  
Bli n di n g  
T he i de ntit y of test a n d c o ntr ol tr eat me nts will n ot be k n o w n t o I n vesti gat ors, S p o ns or, researc h 
staff, patie nts, or t he 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 nistr ati o n of st u d y treat me nts:  
•  
Access t o t he r a n d o mizati o n c o des will be strictl y c o ntr olle d b y t he I R T.  
•  
T hr o u g h o ut t he 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 nc y w he n 
k n o wle d ge of t he patie nt’s st u d y me dicati o n is necessar y f or f urt her ma na ge me nt or if 
r e q uir e d f or r e g ulat or y r e 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 ge nc y 
bli n d br ea k, if at all p ossi ble, pri or t o  t he u n bli n di n g. 
•  
T he A K 0 0 2 a n d place b o f or i nf usi 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 peri p heral he mat ol o g y differe ntial cells will 
n ot be pr o vi de d t o t he I n vesti gat or a n d S p o ns or u ntil after data base l oc k. Rea l-ti me safet y 
m o nit ori n g of diff er e ntial cells will be c o n d ucte d b y t he Safet y M o nit or.  
•  
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 vesti gat or a n d S p o ns or u ntil after data base l oc k.  
•  
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 will n ot be pr o vi de d 
t o t he I n vesti gat or a n d S p o ns or u ntil after data base l oc k, u nless re q uire d f or i m me diate 
saf et y r eas o ns.  
•  
After t he i nitial i nf usi o n of st u d y dr u g a n d pri or t o e nteri n g i nt o t he O L E peri o d of  t he 
st u d y (if a p plica ble), r es ults of t he assess me nts n ote d bel o w will n ot be pr o vi de d t o t he 
I n vesti gat or a n d S p o ns or u ntil after data base l oc k, s o as t o n ot i ntr o d uce bias. T he res ults 
will be r e vie we 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 escal ate d as a p pr o priate.  
− Diff er e ntial 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.  
− E n u mer ati o n of e osi n o p hils a n d  
 fr o m t he Da y 1 6 9 E G D a n d c ol o n osc o p y 
bi o psies. 
Ot her t ha n u n der t he c o n diti o ns descri be d a b o ve, t he st u d y bli n d will be re 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 6. 4 . 
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 6 1 of 1 4 0 
C o nfi de nti al  
1 0. 4  
Bre a ki n g t he Bli n d  
Br ea ki n g t he bli n d i n a cli nical trial 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 tr eat me nt t o w hic h a patie nt was all ocate d w o ul d ha ve i m plicati o ns f or t he 
e mer ge nc y me dical ma na ge me nt of t he patie nt , if re q uire d f or re g ulat or y re p orti n g, or if t here is 
a pr e g na nc y d uri n g t he pr e g na nc y r e p orti n g peri o d.  
If necessar y, e mer ge nc y br ea ki n g of t he bli n d ca n be c o n d ucte d t hr o u g h t he I R T b y re gistere d 
site users a n d/ or t he Me dical M o nit or. W he ne ver p ossi ble, t he I n vesti gat or s h o ul d c o ntact t he 
Me dical M o nit or bef or e a n e mer ge nc y brea ki n g of t he bli n d. Reas o n f or u n bli n di n g, pers o n 
c o n d ucti n g t he u n bli n di n g, 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 date/ti me of 
u n bli n di n g will be r ec or de d.  
1 1.  St u d y P r oce d ures a n d G ui deli nes  
T a ble  2 pr o vi des t he sc he d ule of e ve nts de picti n g t he re q uire d testi n g pr oce d ures t o be 
perf or me d f or t he d ur ati o n of t he st u d y.  
Pr o vi de d visit wi n d o ws m ust  be f oll o we d a n d de viati o ns re p orte d t o t he I nstit uti o nal Re vie w 
B oar d ( I R B) per I R B r e p orti n g r e q uir e me nts . All d osi n g visits m ust be se parate d b y at least 
2 2 da ys a n d n o m or e t ha n 3 4 da ys 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 he visit a n d i ncl u des t he da y of t he ne xt visit).  
T he Da y 1 6 9 visit is critical f or t he pri mar y e n d p oi nt, a n d it is esse ntial t hat t he i nter val bet wee n 
t he last d ose of st u d y dr u g ( e. g., t he Da y 1 4 1 visit) a n d t he Da y 1 6 9 E G D or earl y ter mi nati o n 
E G D be at least 2 2 da ys a n d n o m or e t ha n 3 4 da ys (t he i nter val c o u nt starts t he da y after t he visit 
a n d i ncl u des t he da y of t he ne xt visit). A visit c o n d ucte d o utsi de of t his i nter val ma y i m pact t he 
efficac y assess me nt a n d m ust be a v oi de d. C o ntact Alla k os i m me diatel y if t his occ urs or if it ma y 
occ ur.  
W he n m ulti ple e val uati o ns ar e sc he d ule d at t he sa me ti me p oi nt, t he pri orit y f or eac h will be as 
f oll o ws:  
•  
 (self-a d mi nister e d f or mat) (A p pe n di x 2 ) s h o ul d be c o m plete d at t he be gi n ni n g of t he 
st u d y visit bef or e a n y ot her assess me nts or pr oce d ures.  
•  
P R O q uesti o n nair e  (A p pe n di x 1 ), f oll o we d b y a d diti o nal q uesti o ns re gar di n g d ys p ha gia a n d 
c o nsti pati o n ( A p pe n di x 1 0 ), s h o ul d be c o m plete d b y eac h patie nt dail y (at a p pr o xi matel y 
t he sa me ti me eac h da y) d uri n g t he scree ni n g, treat me nt, a n d f oll o w-u p peri o ds.  
•  
Patie nts will r ate t heir i m pr essi o n of disease se verit y 
 A p pe n di x 8 ) a n d disease 
i m pr o ve me nt 
 A p pe n di x 9 ) at s pecifie d ti me p oi nts d uri n g t he st u d y.  
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Page 62 of 140 
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• 
Vital signs will be obtained after the patient has been at rest for ≥5 minutes.  
• 
Physical examinations can be performed, and urine samples can be collected either before 
or after other evaluations, unless otherwise specified.  
11.1 
Dietary and Lifestyle Restrictions 
Patients should maintain the same diet and food restrictions from the screening visit through the 
End-of-Study visit. Compliance with previous dietary and lifestyle restrictions will be captured 
in the eCRF at each study visit. 
11.2 
Pharmacodynamic/Efficacy-Related Procedures 
11.2.1 
EG/EoD PRO Questionnaire  
An electronic version of the EG/EoD PRO Questionnaire (Appendix 1) will be completed daily 
at approximately the same time of day, by the patient, throughout the study.  
Patients will not be able to complete a questionnaire more than 24 hours after it is due and will 
only be able to go back and make corrections or changes to the data originally entered with the 
approval of the Investigator and electronic data capture system (EDC) vendor. The PRO 
information will be automatically captured and maintained in the ePRO system of the EDC.  
A paper version of the PRO questionnaire is available to patients in case they are not able to 
complete the electronic version for a short period of time. Only 1 PRO questionnaire should be 
completed per day, and the recall period should not be more than approximately 24 hours long. 
This information will be manually captured and entered into the EDC by the study site.  
Post-dose PRO completion during Study Days 155–168 is critical for the primary endpoint, and 
the study site should carefully monitor PRO completion compliance by the patient during this 
period and immediately contact patients who are not sufficiently compliant. Poor PRO 
completion compliance during Study Days 155–168 may impact the efficacy assessment and 
must be avoided. Contact Allakos immediately if this occurs or if it may occur. 
Additional Questions: Patients will complete an extra question each about dysphagia and 
constipation during the screening period and throughout the study. A paper version of these 
questions (Appendix 10) is available if the website is not accessible or the patient does not have 
internet access. These will be completed following the electronic PRO questionnaire. 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 6 3 of 1 4 0 
C o nfi de nti al  
1 1. 2. 2  
 
A n electr o nic versi o n of t he 
 (A p pe n di x 2 ) will be 
c o m plete d b y t he patie nt at t he scr ee ni n g visit, pre d ose o n i nf usi o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, a n d 
1 4 1 a n d o n f oll o w -u p Da y  1 7 6 a n d Da y  1 9 7 or 3 5 ( ± 3) da ys a n d 5 6 ( ± 3) da ys after last d ose of 
st u d y dr u g if E T. T his i nf or mati o n will be a ut o maticall y ca pt ure d a n d mai ntai ne d i n t he E D C.  
A pa per versi o n of t his q uesti o n nair e will als o be a vaila ble f or c o m pleti o n i n case t he electr o nic 
q uesti o n nair e is n ot a vaila ble t o t he patie nt. T his i nf or mati o n will be e ntere d i nt o t he E D C b y t he 
st u d y site.  
1 1. 2. 3  
 a n d 
 
A n electr o nic versi o n of t he 
 (A p pe n di x 9 ) will be 
c o m plete d b y t he patie nt o n St u d y Da y 7 a n d Da y 2 8 a n d Da y 2 2 5 or E T. A n electr o nic versi o n 
of t he 
 (A p pe n di x 8 ) will be c o m plete d b y t he 
patie nt o n Scr ee ni n g Da y  1 9 as well as o n St u d y Da y 7 a n d Da y 2 8 a n d Da y 2 2 5 or E T. A pa per 
versi o n of t hese q uesti o n nair es will als o be a vaila ble f or c o m pleti o n i n case t he electr o nic 
q uesti o n nair e is n ot a vaila ble t o t he patie nt. T his i nf or mati o n will be e ntere d i nt o t he E D C b y t he 
st u d y site.  
1 1. 2. 4  
E G D a n d C ol o n osc o p y wit h Bi o ps y  
A n E G D a n d c ol o n osc o p y wit h bi o ps y will be perf or me d d uri n g t he scree ni n g peri o d a n d o n 
Da y  1 6 9 ( ± 3) or 2 8 ( ± 3) da ys after last d ose of st u d y dr u g if E T. If t he last i nf usi o n o n Da y 1 4 1 
occ urs o utsi de t he pr ot oc ol -s pecifie d wi n d o w, t he E G D a n d c ol o n osc o p y date s h o ul d be m o ve d 
s o t hat it occ urs 2 8 ( ± 3) da ys fr o m t he date of last d ose, e ve n if t his d oes n ot fall o n Da y 1 6 9  ( ± 3). 
T he Da y 1 6 9 visit is critical f or t he pri mar y e n d p oi nt, a n d it is esse ntial t hat t he i nter val bet wee n 
t he last d ose of st u d y dr u g ( e. g., t he Da y 1 4 1 visit) a n d t he Da y 1 6 9 E G D or earl y ter mi nati o n 
E G D be at least 2 2 da ys a n d n o m or e t ha n 3 4 da ys (t he i nter val c o u nt starts t he da y after t he visit 
a n d i ncl u des t he da y of t he ne xt visit). A visit c o n d ucte d o utsi de of t his i nter val ma y i m pact t he 
efficac y assess me nt a n d m ust be a v oi de d. C o ntact Alla k os i m me diatel y if t his occ urs or if it ma y 
occ ur.  
Bi o ps y sa m ples will be c ollecte d o n t he sa me da y , w he ne ver p ossi ble , acc or di n g t o sta n dar dize d 
i nstr ucti o ns a n d will be se nt t o t he ce ntral la b orat or y ( or desi g nee) f or fi xi n g a n d stai ni n g. 
A d diti o nal bi o psies will be c ollecte d f or e x pl orat or y a nal ysis. A n y st ore d tiss ue fr o m bi o psies 
ma y be use d f or e x pl or at or y a nal ysis. Patie nts wit h a hist or y of E o E a n d/ or wit h a sc ore of ≥3 o n 
t he d ys p ha gia q uesti o n d uri n g scr ee ni n g will als o ha ve es o p ha geal bi o psies c ollecte d d uri n g t he 
E G D at scr ee ni n g a n d p ost d ose.  
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Protocol AK002-021 
Amendment 2 
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Page 64 of 140 
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A blinded central reader will report, among other things, maximum number of eosinophils per 
hpf and maximum number of tryptase-positive mast cells per hpf, and gastric biopsies will be 
graded using the Sydney System on inflammation, metaplasia, atrophy, and reactive gastropathy. 
The Marsh Scale Classification will be used to grade duodenal samples.  
Post-treatment EGD and colonoscopy results will not be provided to the Investigator and 
Sponsor until after database lock. The Safety Monitor will review the EGD and colonoscopy 
results and report any issues for escalation to the Medical Monitor and the clinical site, as 
appropriate, while maintaining the blind. 
The screening EGD and colonoscopy with biopsy will be used to determine the following 
inclusion/exclusion criteria as related to the EGD only, and the results must be available from the 
central reader before the patient’s eligibility can be verified. 
• 
Inclusion Criterion #3: Baseline endoscopic biopsy with ≥30 eosinophils/hpf in at least 
3 hpf in the duodenum without any other significant cause for the eosinophilia.  
• 
Exclusion Criterion #2: Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the 
gastric mucosa.  
• 
Exclusion Criterion #6: Active H. pylori infection as confirmed by stool antigen test for 
H. pylori. 
Note: A diagnosis of active H. pylori at screening (by stool antigen test or as detected in 
tissue biopsies by the central pathologist) will result in a screen failure. After 
H. pylori treatment and an additional 6 weeks later, the subject may be reconsented 
and will receive a new subject identification number. 
• 
Exclusion Criterion #7: History of IBD, other chronic inflammatory diseases in the colon 
(with the exception of eosinophilic colitis), celiac disease, achalasia, or esophageal surgery. 
For the colonoscopies with biopsy, a central reader will report, among other things, maximum 
number of eosinophils per hpf and maximum number of tryptase-positive mast cells per hpf for 
each colonic biopsy specimen. Samples from the colonoscopy will include biopsies of the 
terminal ileum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. 
Instructions on collection and processing of biopsies are detailed in the Histology Manual. 
Prior EGD and colonoscopy biopsy samples may be used for eligibility as long as the procedures 
were performed within 45 days of the AK002-021 screening window for the AK002-021 study 
and were performed and centrally assessed using the same criteria as for the AK002-021 study, 
and there were no changes to EoD therapy following the EGD. 


 
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11.2.5 
Complete Blood Count with Differential 
Blood will be obtained for CBC with differential, including absolute eosinophil count, at the 
screening visit, once on Days 8, 15, and 169, and during each follow-up visit or ET visit, as well 
as predose and 1 hour (±15 minutes) postdose on Days 1, 29, 57, 85, 113, and 141. The blood 
sample will be processed and shipped in accordance with the Laboratory Manual instructions. 
A central laboratory will analyze the blood sample and provide results for CBC with differential 
including hemoglobin, hematocrit, platelet count, red blood cell count, white blood cell count, 
and absolute differential count (neutrophils, lymphocytes, monocytes, eosinophils, and 
basophils).  
The blood differential test results (neutrophils, eosinophils, basophils, monocytes, and 
lymphocytes) will be blinded from the Investigator and Sponsor from postdose Day 1 through 
Day 225 or ET and until database lock has occurred. As described in the Investigator’s Brochure, 
these are part of the expected effects of AK002 and could potentially serve to introduce bias in 
blinded members of the study. The Safety Monitor will have real-time access to these laboratory 
results and will review and escalate any concerns/issues to the Medical Monitor and/or the site as 
appropriate. An unscheduled CBC with differential may be collected if requested by the Safety 
Monitor. All panic alerts for blinded values will be sent to the Safety Monitor and evaluated in 
real time. 
11.2.6 
Baseline Diet Assessment and Compliance 
During the screening visit the Investigator or designee will ask the patient a standardized series 
of dietary assessment questions (Appendix 3). This baseline diet assessment involves questions 
regarding food behavior and patterns, as well as types of foods generally avoided, and will serve 
to establish the baseline diet. Answers will be documented in the source documents and recorded 
in the eCRF.  
This baseline diet should be maintained, as much as possible, throughout the course of the study, 
even if symptoms improve. Compliance with the baseline diet will be assessed at study visits on 
Days 1, 15, 29, 57, 85, 113, 141, 176, 197, and 225 or 35,56, and 84 (±3) days after last dose of 
study drug if ET. Whether or not the patient has maintained the baseline diet and what deviations 
were made, if applicable, should be documented in the source documents and the eCRF.  
11.2.7 
Previous Treatments and Procedure Review 
During the screening visit the Investigator or designee will ask the patient about previous EGD 
and colonoscopy procedures and various treatments or methods of symptom control that they 
have tried in relation to their EoD symptoms. These may be under the supervision of a doctor or 
self-attempted by the patient. These may include medications (prescription or over-the-counter), 


 
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food type/eating avoidance or adaptive behaviors, as well as alternative medicine (i.e., 
acupuncture or hypnotic therapy). See Appendix 11. 
11.3 
Safety-Related Procedures 
11.3.1 
Concomitant Medications 
All concomitant medication and concurrent therapies will be documented at screening and at 
study visits if changes are made. Dose, route, unit, frequency of administration, indication for 
administration, and dates of medication will be captured. Any prior medication received within 
30 days before screening and during the study through Day 225 (±3) or 84 (±3) days after last 
dose of study drug, if ET, will be recorded, or through the first dose of study drug if patient 
enters the OLE period of the study. Any medications taken for EoD or EoD-related symptoms at 
any time (even if longer than 30 days before screening) should be listed as concomitant 
medications, even if the medications were discontinued prior to study participation. 
For patients participating in the OLE period, concomitant medications should be recorded in the 
AK002-021 treatment period database up until the first open-label dose is administered after the 
Day 176 visit. This includes the prednisone premedication administered prior to the first dose 
administration visit in the OLE period, which should be recorded in the Concomitant 
Medications CRF of both the AK002-021 treatment period database and the AK002-021 OLE 
period database. Rescue medications and procedures must be documented as rescue treatment in 
the source documents and on the Prior and Concomitant Medications eCRF. 
11.3.2 
Complete Physical Examination 
A complete physical exam will be performed by either the Investigator or a qualified designee 
during the screening visit. A complete physical exam will include the following body system or 
organ assessments: skin; head, eyes, ears, nose, and throat (HEENT); thyroid; lungs; 
cardiovascular; abdomen; extremities; lymph nodes; and a brief neurological examination.  
11.3.3 
Body Weight and Height 
At screening, height in cm and weight in kg will be measured and body mass index (BMI) will 
be calculated. On Days 1, 29, 57, 85, 113, and 141 only, weight will be calculated predose and 
used to determine the amount of study drug to be administered. Body weight will be entered into 
the IRT for each dosing visit and will also be recorded on the IP Dose Calculation and 
Preparation Worksheet that the pharmacist will maintain and document each patient’s dose 
calculations. Body weight should be collected on site on the day of each study drug infusion or 
the day prior to each infusion. Body weight will also be captured on Days 176 (±3), 197 (±3), 
and 225 (±3) or 35 (±3), 56 (±3), and 84 (±3) days after last dose of study drug if ET. 


 
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11.3.4 
Stool Sample for Ova and Parasite 
At screening, fecal collection kits will be provided to patients for the ova and parasite test. 
Patients will return the sample to the site during the screening period, within 1 day of collection. 
The site will ship samples to a central laboratory where they will be tested for the presence of 
ova and/or parasites. A negative result for helminthic parasites must be obtained from the central 
laboratory prior to randomization into the study (Day 1).  
A sample collected and analyzed by the central laboratory within 30 days prior to screening may 
be used to satisfy eligibility for the AK002-021 study, and a duplicate sample does not have to be 
collected. 
11.3.5 
Symptom-Directed Physical Examination 
A symptom-directed physical exam of reported or observed patient symptoms warranting 
examination (in the opinion of the Investigator), including assessments of possible infusion site 
reactions and IRR, will be performed by either the Investigator or a qualified designee at all 
study visits during the treatment period and follow-up period. New, abnormal physical exam 
findings must be documented and will be followed by the Investigator or Subinvestigator at the 
next scheduled visit or sooner if clinically indicated or referred to a non-study physician.  
11.3.6 
Electrocardiogram 
An ECG will be obtained during screening after the patient has been in the required position for 
≥5 minutes and before any blood draw. The Investigator or Subinvestigator will review and 
assess any abnormalities on the ECG in terms of clinical significance. The ECG (without 
intensive QT analysis) will be used to identify diseases or conditions that would put the patient at 
increased risk if participating in a clinical study, so this should be taken into consideration when 
evaluating eligibility for entry into the study. 
11.3.7 
Vital Signs 
Vital signs including systolic and diastolic blood pressure, pulse, body temperature, and 
respiratory rate will be taken after the patient has been at rest for ≥5 minutes and before any 
blood draw (except for post-infusion when vital signs will be obtained as described below).  
On dosing days, vital signs will be measured within 30 minutes predose, 15 (±5) minutes after 
the start of infusion, immediately following the end of infusion (+15 minutes), and just prior to 
discharge. Refer to the schedule of assessments in Table 2. 


 
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11.4 
Clinical Laboratory Measurements  
Blood and urine samples for clinical safety laboratory tests will be collected at the time points 
described below and in Table 2. Investigators may have additional laboratory tests performed for 
the purpose of planning treatment administration or following AE or abnormal laboratory values. 
The site will process and ship blood and urine samples per central laboratory instructions. A 
central laboratory or designee will analyze blood and urine samples and provide results for the 
clinical safety laboratory tests.  
Clinical laboratory testing may be performed locally if the site thinks the central lab may not be 
able to provide results in a timely fashion due to staff reductions, shipping issues, or other factors 
associated with the coronavirus pandemic. The site will strive to use the central laboratory 
whenever possible. 
For any laboratory test value outside the reference range, the Investigator will determine clinical 
significance: Not Clinically Significant (NCS) or Clinically Significant (CS). An abnormal 
laboratory value should be deemed CS if any of the following conditions are met: 
• 
The abnormality suggests a disease and/or organ toxicity that is new or has worsened from 
baseline. 
• 
The abnormality is of a degree that requires additional active management, e.g., change of 
study drug dose, discontinuation of the study drug, close observation, more frequent 
follow-up assessments, or further diagnostic investigation. 
Therefore, a clinically significant lab value is one that indicates a new disease process, an 
exacerbation or worsening of an existing condition, or requires further action to be taken.  
For any laboratory test value outside the reference range that the Investigator considers clinically 
significant, the Investigator will: 
• 
Repeat the test to verify the out-of-range value. 
• 
Follow the out-of-range value to a satisfactory clinical resolution. 
• 
Record as an AE any laboratory test value after start of study drug that: 
− The Investigator considers clinically significant. 
− Requires a patient to be discontinued from the study. 
− Requires a patient to receive treatment. 
Blood will be obtained for CBC with differential as described in Section 11.2.5. 


 
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11.5 
Blood Chemistry Profile 
Blood will be obtained for chemistry tests at screening and predose on dosing Days 1, 29, 57, 85, 
113, and 141 as well as Days 8, 15, 169, 176, 197, and 225 or 28 (±3), 35 (±3), 56 (±3), and 
84 (±3) days after last dose of study drug if ET. The blood sample will be processed and shipped 
in accordance with the Laboratory Manual and laboratory kit instructions. A central laboratory 
will analyze the serum sample and provide results for chemistry tests including sodium, 
potassium, chloride, bicarbonate, glucose, blood urea nitrogen, creatinine, creatine kinase, 
calcium, phosphorus, magnesium, total and direct bilirubin, total protein, albumin, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-
glutamyl transferase (GGT), and lactate dehydrogenase. 
11.5.1 
Pregnancy Test and Follicle-Stimulating Hormone 
A serum pregnancy (hCG) test will be completed for all female patients of childbearing 
potential. Women who are surgically sterile (tubal ligation, partial or total hysterectomy, or 
bilateral oophorectomy) for at least 3 months or those who are postmenopausal for at least 1 year 
with FSH level >30 MIU/mL are not considered to be of childbearing potential. At screening, 
FSH levels will be tested for female patients to confirm postmenopausal vs. childbearing status. 
Both FSH and hCG samples will be processed by the central laboratory. 
Patients with FSH levels ≤30 MIU/mL are considered to be of childbearing potential. For 
patients of childbearing potential, the site will perform a urine dipstick pregnancy test prior to 
each study drug dosing and at Day 176 and Day 197 (±3) or 35 (±3) days and 56 (±3) days after 
last dose of study drug if ET. This test is to be assessed by the study staff prior to the start of 
each study drug infusion. If a patient has a positive pregnancy test, dosing will immediately be 
discontinued. 
To ensure patient safety, each pregnancy in a patient that received study drug must be reported 
within 24 hours of learning of its occurrence. If the patient received AK002, the pregnancy 
should be followed up to determine outcome, including spontaneous or voluntary termination, 
details of the birth, and the presence of absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. If the patient received AK002, any SAE experienced 
during pregnancy must be reported on the SAE Report Form.  
11.5.2 
Urinalysis 
Urine will be obtained for urinalysis at screening, on Day 29, at the ET visit, and symptom-
based, as necessary. The urine sample will be processed and shipped in accordance with the 
Laboratory Manual and laboratory kit instructions. A central laboratory will analyze the urine 
sample for specific gravity, pH, protein, glucose, ketones, blood, and leukocyte esterase.  


 
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11.5.3 
Serology 
Blood will be obtained at screening for serology tests including hepatitis B surface antigen 
(HBsAG), hepatitis C antibody, hepatitis B core antibody (anti-HBc), and human 
immunodeficiency virus (HIV). The blood sample will be processed and shipped to the central 
laboratory in accordance with the Laboratory Manual and lab kit instructions. A positive result 
will be verified by appropriate reflex testing. A positive result, if clinically significant (and not 
due to previous vaccination or resolved disease or exposure) will exclude the patient from 
enrollment. See Appendix 12. 
11.5.4 
Anti-AK002 Antibodies 
Blood will be collected for determination of ADA at screening, and predose on Days 1, 29, 57, 
85, and on Day 169 and Day 225 or 84 (±3) days after last dose of study drug if ET. An 
unscheduled blood sample for ADA may also be obtained if a related AE suspected of being 
associated with immunogenicity occurs. The serum sample will be collected predose and 
processed and shipped in accordance with the laboratory manual and lab kit instructions. 
A central laboratory will analyze the sample for anti-AK002 antibodies using a validated assay 
method. 
11.5.5 
Blood for Pharmacokinetics and Storage 
Blood samples for serum PK assessments will be collected during the screening period as well as 
predose on dosing Days 29, 57, 85,113, and 141 and on Days 8, 15, 169, 176, 197, and 225 or 
28, 35, 56, and 84 (±3) days after last dose of study drug, if ET. The serum samples will be 
collected predose and processed and shipped frozen in accordance with the study Laboratory 
Manual and lab kit instructions.  
AK002 concentrations will be determined by the central laboratory or designee using a validated 
ELISA method. Specific information on PK sample collection, processing, storage, and shipment 
will be provided in the laboratory manual.  
11.5.6 
Blood for Histamine and Tryptase 
If anaphylaxis is suspected, a blood sample should be obtained for plasma histamine level and 
tryptase within 1–2 hours of the onset of symptoms. The sample will be sent to the central 
laboratory for processing. Refer to Appendix 6 for more details.  
11.5.7 
Blood for IgE 
Blood will be collected for determination of serum IgE levels and sent to the central laboratory 
for processing. Blood will be collected during screening and on follow-up Day 176 (±3) or 
35 (±3) days after last dose of study drug if ET. 


 
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11.5.8 
Blood for Strongyloides stercoralis 
Blood collected for the screening serology sample will be tested for Strongyloides stercoralis. 
The sample will be processed by the central laboratory. A negative result must be available prior 
to the first dose of study drug.  
In case of a positive Strongyloides stercoralis test result, the patient must be screen failed and 
should be treated with standard therapies. If symptoms remain consistent, patient may be 
reconsented and receive a new patient number 4 weeks after completion of therapy. 
11.5.9 
COVID-19 Testing 
Testing for COVID-19 is not required for this study but may be implemented by the study site at 
any time during the study due to safety regulations or procedures. Testing for COVID-19 may be 
individually mandated by EGD facilities or study sites, and if this is required, will be consented 
through the site and not listed in the AK002-021 ICF.  
11.6 
Effective Methods of Contraception for Allakos Studies 
This section applies to study subjects who are women of childbearing potential (WOCBP), and 
male study subjects whose sexual partners are WOCBP.  
Abstinence is the only birth control method that is 100% effective in preventing pregnancy. For 
subjects who do not practice abstinence, Allakos recommends that study subjects use highly 
effective methods of contraception, which include:  
• 
Permanent Sterilization: Tubal ligation, vasectomy – 99% effective  
• 
Long-Acting Reversible Contraceptives (LARC):  
− IUD – 99% effective  
− Implantable rod (matchstick sized rod that contains progestin hormone implanted under 
the skin of the upper arm; prevents ovulation) – 99% effective  
• 
Contraceptive Injection:  
− Intramuscular or SC injection of progestin hormone every 3 months – 96% effective  
• 
Short-Acting Hormonal Methods:  
− Oral contraceptives or patch – 91% effective  
− Vaginal contraceptive ring (releases 2 hormones, progestin and estrogen, to prevent 
ovulation) – 91% effective  
Note: Effectiveness rates obtained from the Birth Control Guide on the FDA web site 
(FDA, 2021).  


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 2 of 1 4 0 
C o nfi de nti al  
Barrier a n d ot her met h o ds n ot liste d a b o ve w he n use d t o get her as d ual met h o d s s uc h as a 
c o n d o m + dia p hr a g m or c o n d o m + s per mici de are less effecti ve met h o ds. Theref ore , t hese d ual 
met h o ds ar e n ot r ec o m me n de d as t he y c o ul d i ncrease t he ris k of bec o mi n g pre g na nt d uri n g t he 
st u d y or f oll o w-u p peri o d. W he n usi n g d ual met h o ds, at least  1 of t he met h o ds s h o ul d be a 
hi g hl y eff ecti ve met h o d of c o ntr ace pti o n.  
S u bjects w h o e nter e d t he st u d y usi n g d ual met h o ds of c o ntrace pti o n t hat d o n ot i ncl u de at least 
1 of t he hi g hl y eff ecti ve met h o ds of c o ntrace pti o n are all o we d t o c o nti n ue i n t he st u d y  b ut m ust 
be i nf or me d of t he ris ks of n ot usi n g hi g hl y effecti ve met h o ds of c o ntrace pti o n.  
1 2.  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 ur es b y visit ar e s h o w n i n T a ble  2. 
Ge ner al I nf or mati o n:  
•  
All r ec or de d cl oc k ti mes s h o ul d utilize a 2 4 -h o ur cl oc k.  
•  
Da y 1 is t he da y of t he first i nf usi o n.  
•  
Pr oce d ur es f or scr ee ni n g ma y be perf or me d o ver t he c o urse of m ulti ple vi sits pri or t o t he 
first i nf usi o n. 
1 2. 1  
Scree ni n g P eri o d  
1) 
O btai n writte n i nf or me d c o nse nt.  
2) 
Assi g n t he partici pa nt a PI D.  
3) 
Be gi n t he c ollecti o n of S A E r elate d t o a n y scree ni n g acti vities.  
4) 
C ollect de m o gr a p hics a n d me dical hist or y.  
5) 
Rec or d pri or a n d c o n c o mita nt me dicati o ns. 
6) 
Deter mi ne b o d y wei g ht a n d hei g ht.  
7) 
Acti vate patie nt access t o t he e P R O q uesti o n naire p ortal a n d i nstr uct patie nt o n use of t he 
we bsite t o c o m plete t he q uesti o n naire(s). Use t he e P R O T eac hi n g T o ol t o i nstr uct t he 
patie nt o n use of t he electr o nic platf or m ( A p pe n di x 7 ). 
8) 
 t o be c o m plete d b y t he patie nt. 
9) 
Perf or m baseli ne diet assess me nt.  
1 0) C o m plete pr e vi o us tr eat me nts  a n d pr oce d ure re vie w. 
1 1) O btai n vital si g ns b ef or e bl o o d dra ws a n d after patie nt at rest ≥5 mi n utes.  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 3 of 1 4 0 
C o nfi de nti al  
1 2) Perf or m a c o m plete p h ysical e xa mi nati o n.  
1 3) O btai n a 1 0 -lea d or 1 2-lea d E C G bef ore bl o o d dra w. 
1 4) C ollect t he f oll o wi n g sa m ples f or t he ce ntral la b orat or y:  
a)  Bl o o d f or C B C wit h diff er e ntial  
b) 
Bl o o d f or C he mistr y ( sa m ple t o be teste d f or F S H a n d h C G if patie nt is of 
c hil d beari n g p ote ntial)  
c)  Uri nal ysis  
d) 
Bl o o d f or ser ol o g y testi n g (i ncl u des Str o n g yl oi des sterc oralis ) 
e)  Bl o o d f or P K  
f) 
Bl o o d f or A D A  
g) 
Bl o o d f or t otal ser u m I g E  
1 5) Pr o vi de patie nt a st o ol c ollecti o n kit a n d as k patie nt t o pr o vi de a st o ol sa m ple w hile o n site 
or r et ur n it t o t he site wit hi n 1 da y of c ollecti o n.  
1 6) Perf or m a scr ee ni n g E G D a n d c ol o n osc o p y wit h bi o ps y f oll o wi n g i nstr ucti o ns pr o vi de d b y 
Alla k os a n y ti me d uri n g t he scr ee ni n g peri o d.  T he E G D a n d c ol o n osc o p y s h o ul d ta ke place 
o n t he sa me da y i n or der t o mi ni mize effects of pr oce d ure pre me dicati o n o n t he P R O 
sc or es. Patie nt s h o ul d arri ve f asti n g f or t he E G D pr oce d ure as s pecifie d b y i nstr ucti o ns 
fr o m t he E G D pr o vi der.  
1 7) 
 t o be c o m plete d b y t he patie nt o n scree ni n g Da y 1 9 ( n ot a cli nic visit).  
1 8) Usi n g res ults fr o m t he ce ntr al hist ol o g y rea der, c o nfir m t hat t he e osi n o p hil c o u nt fr o m t he 
gastric a n d/ or d u o de nal bi o psies q ualif y t he patie nt f or t he st u d y a n d n o e xcl usi o nar y 
criteria ar e f o u n d o n t he E G D  or c ol o n osc o p y. 
1 9) Re vie w all e P R O sc or es. Si nce t he b o wel pre parati o ns c o ul d artificiall y i ncrease t he sc ores, 
e xcl u de e P R O sc or es f ro m t he da y bef ore a n d t he da y of c ol o n osc o p y w he n assessi n g 
eli gi bilit y criteria. 
1 2. 2  
P ri or t o D a y 1  
T he f oll o wi n g pr oce d ur es will be perf or me d pri or t o Da y 1:  
1) 
Patie nt s h o ul d self -a d mi nister 8 0 m g oral pre d nis o ne ( or alter nati ve pre me dicati o n 
a p pr o ve d b y t he Me dical M o nit or) 1 2 – 2 4 h o urs pri or t o i nf usi o n start. Patie nt s h o ul d 
r e me m ber w hat ti me t he y t o o k t he pre me dicati o n. T his 8 0 m g oral pre d nis o ne is o nl y 
all o we d o n Da y 1, u nless pr ea p pr o ve d b y t he Alla k os Me dical M o nit or . 
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 4 of 1 4 0 
C o nfi de nti al  
1 2. 3  
D a y 1 – R a n d o miz ati o n/I nf usi o n 1  
1) 
Pri or t o t he i nf usi o n:  
a)  Assess t he patie nt f or S A E r elate d t o scree ni n g pr oce d ures.  
b) 
C o nfir m c o nti n ui n g eli gi bilit y.  
c)  D oc u me nt a n y c ha n ges t o healt h stat us.  
d) 
D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns.  
e)  D oc u me nt a n y c ha n ges t o baseli ne diet.  
f) 
 
g) 
C o nfir m  
 was c o m plete d electr o nicall y o n Scree ni n g Da y 1 9. I f it was n ot 
c o m plete d, ha ve patie nt c o m plete a pa per versi o n of t he q ues ti o n naire. 
h) 
Deter mi ne b o d y wei g ht.  
i) 
Perf or m uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial . 
j) 
C ollect vital si g ns wit hi n 3 0 mi n utes of t he start of t he i nf usi o n. 
k) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, if nee de d.  
l) 
Bl o o d f or C B C wit h  diff er e ntial  
m) 
Bl o o d f or C he mistr y  
2) 
Pri or t o r a n d o mizi n g t he patie nt i n t he I R T s yste m, t he site will i de ntif y t he hi g hest wee kl y 
T S S of disease acti vit y r ec or de d d uri n g  t he scree ni n g peri o d ( pri or t o Da y 1) i n or der t o 
str atif y patie nts t o T S S ≥2 8 or T S S < 2 8 as ca pt ure d i n t he patie nt P R O. T he st u d y 
c o or di nat or or desi g nee will e nter t he hi g hest wee kl y  T S S i nt o t he I R T o n St u d y Da y 1 t o 
str atif y t he patie nt. 
3) 
T he I R T s yste m will r a n d o ml y assi g n t he patie nt t o A K 0 0 2 at a d ose 3  m g/ k g f or 6  d oses or  
place b o 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 
detaili n g t he kit n u m ber(s) t o use t o pre pare t he i nf usi o n, t he d ose t o pre pare ( 3  m g/ k g), a n d 
t he patie nt’s b o d y wei g ht. 
4) 
T he st u d y p har macist will pr e par e st u d y dr u g usi n g t he wei g ht o btai ne d at t he visit. R efer t o 
t he P har mac y Ma n ual f or details o n d ose pre parati o n. 
5) 
I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o ver at least 4 h o urs usi n g a n i nf usi o n p u m p. See t he 
P har mac y Ma n ual f or i nf usi o n rates. Rec or d t he start a n d st o p ti mes of t he i nf usi o n 
i ncl u di n g a n y ti mes t he i nf usi o n is i nterr u pte d. 
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 5 of 1 4 0 
C o nfi de nti al  
b) 
C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of i nf usi o n.  
c)  If a na p h yla xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne 
level 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 ne d if a n i m m u n o ge nicit y -relate d A E is s us pecte d. 
6) 
P ost -i nf usi o n: 
a)  C ollect vital si g ns wit hi n 1 5 mi n utes of t he e n d of t he i nf usi o n.  
b) 
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 he e n d of t he 
i nf usi o n.  
c)  O bser ve t he patie nt f or at least 1 h o ur after t he e n d of i nf usi o n. C ollect vital si g ns j ust 
pri or t o disc har ge.  
1 2. 4  
D a y 7 ( n ot a Cli nic Visit)  
1) 
 (A p pe n di x 8 ) 
2) 
 (A p pe n di x 9 ) 
1 2. 5  
D a y 8 ( ± 2)  
1) 
Assess t he patie nt 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) 
Bl o o d f or C B C wit h diff er e ntial  
4) 
Bl o o d f or C he mistr y  
5) 
Bl o o d f or P K  
1 2. 6  
D a y 1 5 ( ± 2)  
1) 
Assess t he patie nt 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 baseli ne diet c o m plia nce.  
4) 
Assess dail y diar y c o m plia nce (i ncl u di n g a d diti o nal q uesti o ns).  
5) 
C ollect vital si g ns  
6) 
Perf or m s y m pt o m -dir ecte d p h ys ical e xa m, as nee de d 
7) 
Bl o o d f or C B C wit h diff er e ntial  
8) 
Bl o o d f or C he mistr y  
9) 
Bl o o d f or P K  
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 6 of 1 4 0 
C o nfi de nti al  
1 2. 7  
D a y 2 8 ( n ot a Cli nic Visit)  
1) 
 (A p pe n di x 8 ) 
2) 
 (A p pe n di x 9 ) 
1 2. 8  
D a y 2 9 ( ± 3) – I nf usi o n 2 
1) 
Pri or t o t he i nf usi o n: 
a)  Assess t he patie nt f or A E a n d S A E.  
b) 
D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns.  
c)  Assess baseli ne diet c o m plia nce.  
d) 
Assess dail y diar y c o m plia nce (i ncl u di n g a d diti o nal q uesti o ns).  
e)  
 
f) 
Deter mi ne b o d y wei g ht  
g) 
Uri nal ysis  
h) 
Perf or m uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial.  
i) 
C ollect vital si g ns wit hi n 3 0 mi n utes of t he start of t he i nf usi o n. 
j) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
k) 
Bl o o d f or C B C wit h diff er e ntial  
l) 
Bl o o d f or C he mistr y  
m)  Bl o o d f or P K  
n) 
Bl o o d f or A D A  
o) 
T he I R T will be accesse d, a n d t he patie nt’s PI D a n d b o d y wei g ht will be e ntere d.  
2) 
T he st u d y p har macist will pr e par e st u d y dr u g usi n g t he c urre nt b o d y wei g ht o btai n e d a n d 
t he d osa ge ( 3 m g/ k g) a n d kit n u m ber(s) pr o vi de d b y t he I R T.  
3) 
I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o ver at least 1 h o ur usi n g a n i nf usi o n p u m p. See t he 
P har mac y Ma n ual f or i nf usi o n rates. Rec or d t he start a n d st o p ti mes of t he i nf usi o n 
i ncl u di n g a n y ti mes t he i nf usi o n is i nterr u pte d. 
b) 
C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of i nf usi o n.  
c)  If a na p h yla xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne 
le 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 ne d if a n i m m u n o ge nicit y -relate d A E is s us pecte d. 
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 7 of 1 4 0 
C o nfi de nti al  
4) 
P ost -i nf usi o n: 
a)  C ollect vital si g ns wit hi n 1 5 mi n utes of t he e n d of t he i nf usi o n.  
b) 
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 he e n d of t he 
i nf usi o n. 
c)  O bser ve t he patie nt f or at least 1 h o ur after t he e n d of t he i nf usi o n. C ollect vital si g ns 
j ust pri or t o disc har ge. 
1 2. 9  
D a y 5 7 ( ± 3) – I nf usi o n 3 
1) 
Pri or t o t he i nf usi o n:  
a)  Assess t he patie nt f or A E a n d S A E.  
b) 
D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns.  
c)  Assess baseli ne diet c o m plia nce.  
d) 
Assess dail y diar y c o m plia nce (i ncl u di n g a d diti o nal q uesti o ns).  
e)  
 
f) 
Deter mi ne b o d y wei g ht.  
g) 
Perf or m uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial. 
h) 
C ollect vital si g ns wit hi n 3 0 mi n utes of t he start of t he i nf usi o n. 
i) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
j) 
Bl o o d f or C B C wit h diff er e ntial  
k) 
Bl o o d f or C he mistr y  
m)  Bl o o d f or P K  
n) 
Bl o o d f or A D A  
2) 
T he I R T will be accesse d, a n d t he patie nt’s PI D a n d wei g ht will be e ntere d.  
3) 
T he st u d y p har macist or desi g nee will pre pare st u d y dr u g usi n g t he wei g ht o btai ne d at t he 
visit a n d t he d osa ge ( 3 m g/ k g) a n d kit n u m ber(s) pr o vi de d b y t he I R T.  
4) 
I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o ver at least 1 h o ur usi n g a n i nf usi o n p u m p. See t he 
P har mac y Ma n ual f or i nf usi o n rates. Rec or d t he start a n d st o p ti mes of t he i nf usi o n 
i ncl u di n g a n y ti mes t he i nf usi on is i nterr u pte d.  
b) 
C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of i nf usi o n.  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 8 of 1 4 0 
C o nfi de nti al  
c)  If a na p h yla xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne 
le 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 ul e d 
A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge nicit y -relate d A E is s us pecte d. 
5) 
P ost -i nf usi o n: 
a)  C ollect vital si g ns wit hi n 1 5 mi n utes of t he e n d of t he i nf usi o n.  
b) 
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 he e n d of t he 
i nf usi o n. 
c)  O bser ve t he patie nt f or at least 1 h o ur after t he e n d of t he i nf usi o n. C ollect vital si g ns 
j ust pri or t o disc har ge. 
1 2. 1 0  D a y 8 5 ( ± 3) – I nf usi o n 4 
1) 
Pri or t o t he i nf usi o n:  
a)  Assess t he patie nt f or A E a n d S A E.  
b) 
D oc u me nt a n y c ha n ges t o c o nc o mita nt m e dicati o ns.  
c)  Assess baseli ne diet c o m plia nce.  
d) 
Assess dail y diar y c o m plia nce (i ncl u di n g a d diti o nal q uesti o ns).  
e)  
 
f) 
Deter mi ne b o d y wei g ht.  
h) 
Perf or m uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial. 
i) 
C ollect vital si g ns wit hi n 3 0 mi n utes of t he start of t he i nf usi o n. 
j) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
k) 
Bl o o d f or C B C wit h diff er e ntial  
l)  
Bl o o d C he mistr y  
m)  Bl o o d f or P K  
n) 
Bl o o d f or A D A  
2) 
T he I R T will be accesse d, a n d t he patie nt’s PI D a n d b o d y wei g ht will be e ntere d.  
3) 
T he st u d y p har macist will pr e par e st u d y dr u g usi n g t he wei g ht o btai ne d at t he visit a n d t he 
d osa ge ( 3 m g/ k g) a n d kit n u m ber(s) pr o vi de d b y t he I R T. 
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 7 9 of 1 4 0 
C o nfi de nti al  
4) 
I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o ver at least 1 h o ur usi n g a n i nf usi o n p u m p. See t he 
P har mac y Ma n ual f or i nf usi o n rates. Rec or d t he start a n d st o p ti mes of t he i nf usi o n 
i ncl u di n g a n y ti mes t he i nf usi o n is i nterr u pte d. 
b) 
C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he sta rt of i nf usi o n. 
c)  If a na p h yla xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne 
le 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 ne d if a n i m m u n o ge nicit y -relate d A E is s us pecte d. 
5) 
P ost -i nf usi o n: 
a)  C ollect vital si g ns wit hi n 1 5 mi n utes of t he e n d of t he i nf usi o n.  
b) 
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 he e n d of t he 
i nf usi o n. 
c)  O bser ve t he patie nt f or at least 1 h o ur after t he e n d of t h e i nf usi o n. C ollect vital si g ns 
j ust pri or t o disc har ge. 
1 2. 1 1  D a y 1 1 3 ( ± 3) – I nf usi o n 5 
1) 
Pri or t o t he i nf usi o n:  
a)  Assess t he patie nt f or A E a n d S A E.  
b) 
D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns.  
c)  Assess baseli ne diet c o m plia nce.  
d) 
Assess dail y diar y  c o m plia nce (i ncl u di n g a d diti o nal q uesti o ns).  
e)  
 
f) 
Deter mi ne b o d y wei g ht.  
h) 
Perf or m uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial.  
i) 
C ollect vital si g ns wit hi n 3 0 mi n utes of t he start of t he i nf usi o n. 
j) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
k) 
Bl o o d f or C B C wit h diff er e ntial  
l) 
Bl o o d f or C he mistr y  
m)  Bl o o d f or P K  
2) 
T he I R T will be accesse d, a n d t he patie nt’s PI D a n d b o d y wei g ht will be e ntere d.  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 8 0 of 1 4 0 
C o nfi de nti al  
3) 
T he st u d y p har macist will pr e par e st u d y dr u g usi n g t he c urre nt wei g ht a n d t he d osa ge 
( 3 m g/ k g) a n d kit n u m ber(s) pr o vi de d b y t he I R T.  
4) 
I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o ver at least 1 h o ur usi n g a n i nf usi o n p u m p. See t he 
P har mac y Ma n ual f or i nf usi o n rates. Rec or d  t he start a n d st o p ti mes of t he i nf usi o n 
i ncl u di n g a n y ti mes t he i nf usi o n is i nterr u pte d. 
b) 
C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of t he i nf usi o n.  
c)  If a na p h yla xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas ma hista mi ne 
le 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 ne d if a n i m m u n o ge nicit y -relate d A E is s us pecte d. 
5) 
P ost -i nf usi o n: 
a)  C ollect vital si g ns wit hi n 1 5 mi n utes of t he e n d of t he i nf usi o n.  
b) 
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 he e n d of t he 
i nf usi o n. 
c)  O bser ve t he patie nt f or at least 1 h o ur after t he e n d of t he i nf usi o n. C ollect vital si g ns 
j ust pri or t o disc har ge. 
1 2. 1 2  D a y 1 4 1 ( ± 3) – I nf usi o n 6 
1) 
Pri or t o t he i nf usi o n:  
a)  Assess t he patie nt f or A E a n d S A E.  
b) 
D oc u me nt a n y c ha n ges t o c o nc o mita nt me dicati o ns.  
c)  Assess baseli ne diet c o m plia nce.  
d) 
Assess dail y diar y c o m plia nce (i ncl u di n g a d diti o nal q uesti o ns).  
e)  
 
f) 
Deter mi ne b o d y wei g ht.  
h) 
Perf or m uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial. 
i) 
C ollect vital si g ns wit hi n 3 0 mi n utes of start of t he i nf usi o n. 
j) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
k) 
Bl o o d f or C B C wit h diff er e ntial  
l) 
Bl o o d f or C he mistr y  
m)  Bl o o d f or P K  
C CI


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 81 of 140 
Confidential 
2) 
The IRT will be accessed, and the patient’s PID and body weight will be entered. 
3) 
The study pharmacist will prepare study drug using the current weight and the dosage 
(3 mg/kg) and kit number(s) provided by the IRT. 
4) 
Infusion of Study Drug: 
a) Infuse 100 mL of study drug over at least 1 hour using an infusion pump. See the 
Pharmacy Manual for infusion rates. Record the start and stop times of the infusion 
including any times the infusion is interrupted. 
b) Collect vital signs 15 (±5) minutes after the start of the infusion. 
c) If anaphylaxis is suspected, a sample of blood should be obtained for plasma histamine 
level and tryptase within 1–2 hours of the onset of symptoms. Also, an unscheduled 
ADA blood sample may be obtained if an immunogenicity-related AE is suspected. 
5) 
Post-infusion: 
a) Collect vital signs within 15 minutes of the end of the infusion. 
b) Collect blood for CBC with differential 1 hour (±15 minutes) after the end of the 
infusion. 
c) Observe the patient for at least 1 hour after the end of the infusion. Collect vital signs 
just prior to discharge. 
d) Schedule EGD and colonoscopy for Day 169 (±3). 
12.13 Day 169 (±3) or 28 (±3) Days after Last Dose of Study Drug if ET – 
Follow-up EGD and Colonoscopy 
1) 
Patient should arrive fasting for the EGD procedure as specified by instructions from the 
EGD provider. 
2) 
Blood for CBC with differential 
3) 
Blood for Chemistry 
4) 
Blood for PK 
5) 
Blood for ADA 
6) 
Collect AE, SAE, and changes in baseline diet. Collect all concomitant medications 
provided to the patient during the EGD. 
7) 
Perform EGD and colonoscopy with biopsy following procedures provided by Allakos and 
all EGD facility standard operating procedures (SOP). EGD and colonoscopy should take 
place on the same day.  


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 8 2 of 1 4 0 
C o nfi de nti al  
F or E arl y Ter mi n ati o n:  Perf or m E G D a n d c ol o n osc o p y 2 8 ( ± 3) da ys after last d ose of st u d y 
dr u g or pri or t o t his, if necessar y, t o e ns ure c o m plia nce wit h t he visit. If patie nt disc o nti n ues t he 
st u d y m or e t ha n 2 8 da ys after last d ose of st u d y dr u g, perf or m t he E G D a n d c ol o n osc o p y as s o o n 
as p ossi ble.  
If Da y 1 4 1 (Inf usi o n 6) occ urs o utsi de t he pr ot oc ol wi n d o w, d o n ot  c o n d uct t he E G D a n d 
c ol o n osc o p y o n Da y 1 6 9 b ut r at her o n a da y t hat is 2 8 ( ± 3) da ys  after last d ose of st u d y dr u g.  
C o ntact Alla k os f or m or e i nf or mati o n.  
1 2. 1 4  D a y 1 7 6 ( ± 3) or 3 5 ( ± 3) D a ys after L ast D ose of S t u d y Dr u g if E T – 
F oll o w- u p  Visit  1 
1) 
Assess t he patie nt 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 baseli ne diet c o m plia nce.  
4) 
Assess dail y diar y c o m plia nce (i ncl u di n g a d diti o nal q uesti o ns).  
5) 
 
6) 
Deter mi ne b o d y wei g ht.  
7) 
C ollect vital si g ns.  
8) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
9) 
Bl o o d f or C B C wit h diff er e ntial  
1 0) Bl o o d f or C he mistr y  
1 1) Bl o o d f or P K  
1 2) Bl o o d f or t otal ser u m I g E  
1 3) Uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial  
1 4) Patie nts w h o e nter t he O L E peri o d of t he st u d y will be gi n e xte nsi o n d osi n g 1 da y after 
c o m pleti n g t he Da y 1 7 6 pr oce d ures f or t he d o u ble- bli n d peri o d of Pr ot oc ol A K 0 0 2 - 0 2 1. 
Patie nt s ma y r ecei ve t he r e q uir e d pre me dica ti o n f or t he first O L E d osi n g after all of t he 
d o u ble- bli n d Da y 1 7 6 pr oce d ur es  ha ve bee n c o m plete d . 
 
Patie nts will n ot c o m plete t he Da y 1 9 7 or Da y 2 2 5 pr oce d ures u n der t he d o u ble - bli n d 
peri o d of t he st u d y. O pe n -la bel d osi n g a n d f oll o w-u p will occ ur u n der t he O L E sc he d ule  
f or St u d y A K 0 0 2-0 2 1 ( T a ble  8).  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 8 3 of 1 4 0 
C o nfi de nti al  
Eli gi ble patie n ts w h o c h o ose t o partici 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 Assess me nts  (T a ble  8 i n A p pe n di x 1 3 ) a n d will recei ve t he first d ose of o pe n-la bel 
A K 0 0 2 after Da y 1 7 6 a n d after self-a d mi nisteri n g 8 0 m g  pre d nis o ne pre me dicati o n 1 2 – 2 4 h o urs 
pri or t o t he first d ose of A K 0 0 2 i n t he O L E peri o d of t he  pr ot oc ol.  
F or E arl y Ter mi n ati o n:  Perf or m t his visit 3 5 ( ± 3) da ys after last d ose of st u d y dr u g or pri or t o 
t his, if necessar y, t o e ns ur e c o m plia nce wit h t he visit. If patie nt disc o nti n ues t he st u d y m ore t ha n 
3 5 da ys after last d ose of st u d y dr u g, perf or m t he visit as s o o n as p ossi ble. If o nl y 1 E T visit is 
p ossi ble, E G D wit h c ol o n osc o p y a n d F oll o w -u p Visit  1 ma y occ ur o n t he sa me da y. Bl o o d dra ws 
s h o ul d occ ur pri or t o E G D a n d c ol o n osc o p y me dicati o ns, if p ossi ble.  
1 2. 1 5  D a y 1 9 7 ( ± 3) or 5 6 ( ± 3) D a ys after L ast D ose of St u d y Dr u g if E T – 
F oll o w- u p  Visit  2 
1) 
Assess t he patie nt 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 baseli ne diet c o m plia nce.  
4) 
 
5) 
Deter mi ne b o d y wei g ht.  
6) 
C ollect vital si g ns.  
7) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
8) 
Uri ne pr e g na nc y test if patie nt is of c hil d beari n g p ote ntial  
9) 
Bl o o d f or C B C wit h diff er e ntial  
1 0) Bl o o d f or C he mistr y  
1 1) Bl o o d f or P K  
F or E arl y Ter mi n ati o n:  Perf or m t his visit 5 6 ( ± 3) da ys after last d ose of st u d y dr u g or pri or t o 
t his, if necessar y, t o e ns ur e c o m plia nce wit h t he visit. If patie nt disc o nti n ues t he st u d y m ore t ha n 
5 6 da ys after last d ose of st u d y dr u g, perf or m t he visit as s o o n as p ossi ble.  
1 2. 1 6  D a y 2 2 5 ( ± 3) or 8 4 ( ± 3) D a ys after L ast D ose of St u d y Dr u g if E T  
1) 
Assess t he patie nt 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 baseli ne diet c o m plia nce.  
4) 
Perf or m s y m pt o m -dir ecte d p h ysical e xa m, as nee de d.  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 8 4 of 1 4 0 
C o nfi de nti al  
5) 
Deter mi ne b o d y wei g ht.  
6) 
C ollect vital si g ns.  
7) 
Bl o o d f or C B C wit h diff er e ntial  
8) 
Bl o o d f or C he mistr y  
9) 
Bl o o d f or A D A  
1 0) Bl o o d f or P K  
1 1) Uri nal ysis  
1 2) 
 (A p pe n di x 8 ) 
1 3) 
 (A p pe n di x 9 ) 
F or E arl y Ter mi n ati o n:  Perf or m  t his visit 8 4 ( ± 3) da ys after last d ose of st u d y dr u g or pri or t o 
t his, if necessar y, t o e ns ur e c o m plia nce wit h t he visit. If patie nt disc o nti n ues t he st u d y m ore t ha n 
8 4 da ys a fter last d ose of st u d y dr u g, perf or m t he visit as s o o n as p ossi ble.  
1 3.  A d verse E ve nt Re p orti n g a n d D oc u me nt ati o n  
1 3. 1  
A d verse E ve nts  
I n acc or da nce wit h 2 1 C o de of Fe der al Re g ulati o n ( C F R) 3 1 2. 3 2( b) a n d I nter nati o nal 
C o nf er e nce o n Har m o nisati o n (I C H) G ui da 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 utical pr o d uct a n d t hat d oes n ot 
necess aril y ha ve a ca usal r elati o ns hi p wit h t he treat me nt.  
A n A E is t her ef or e a n y u nf a v or a ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or disease te m p or all y ass ociate d wit h t he a d mi nistrati o n of a n i n vesti gati o nal 
pr o d uct, w het her or n ot r elate d t o t hat i n vesti gati o nal pr o d uct. A n u ne x pecte d A E is o ne of a 
t y pe n ot i de ntifie d i n nat ur e, se verit y, or fre q ue nc y i n t he c urre nt I n vesti gat or’s Br oc h ure or of 
gr eater se verit y or fr e q ue nc y t ha n e x pecte d bas e d o n t he i nf or mati o n i n t he I n vesti gat or’s 
Br oc h ur e. E xa m ples of a n A E i ncl u de:  
•  
Si g nifica nt w orse ni n g or e xacer bati o n of u n derl yi n g me dical c o n diti o n.  
•  
Si g nifica nt a b n or mal fi n di n gs fr o m p h ysical e xa ms, vital si g ns, or la b orat or y tests.  
T he f oll o wi n g e xa m p les ar e n ot c o nsi dere d A E: 
•  
Me dical or s ur gical pr oce d ur e, 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.  
C CI
C CI


 
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• 
Anticipated day-to-day fluctuations of preexisting medical conditions (including laboratory 
values) as long as significant worsening from baseline does not occur. 
• 
Signs or symptoms of the disorder being studied unless they become more severe or occur 
with greater frequency than occurring at baseline. 
• 
Normal progression of the disorder being studied unless it is more severe per Investigator 
judgment or occurs with greater speed/frequency than expected. 
All AE, whether elicited by questions from study staff, volunteered, or noted on physical 
examination/laboratory testing, and regardless of causality or severity, will be assessed and 
recorded in the eCRF beginning after the first administration of study drug in the double-blind 
period of the study and ending at the time of study completion or ET of the double-blind period 
or the OLE period, whichever is later.  
For patients participating in the OLE period, AE will be recorded in the CRF of the AK002-021 
double-blind treatment period database up until the start of the first open-label infusion after the 
Day 176 visit and recorded in the CRF of the AK002-021 OLE period database beginning from 
the start of the first open-label infusion after the Day 176 visit. 
13.2 
Serious Adverse Events 
A SAE is defined as an AE that meets that one of the following criteria:  
• 
Death 
• 
A life-threatening AE that places the subject at risk of death at the time of the event. It does 
not refer to an event that hypothetically might cause death if it were more severe.  
• 
Inpatient hospitalization or prolongation of existing hospitalization. 
• 
A persistent or significant disability/incapacity. 
• 
A congenital anomaly/birth defect occurring in the offspring of a study subject.  
• 
Other important medical events may also be considered a SAE when, based on appropriate 
medical judgment, they jeopardize the patient or require intervention to prevent one of the 
outcomes listed above. 
The date that an AE meets 1 of the criteria listed above is the date that it becomes an SAE. 
Conversely, the date that the SAE no longer meets 1 of the criteria listed above is the end date of 
the SAE. A new AE with an outcome of “recovering” may be created to address the ongoing AE 
once it is no longer considered serious. 


 
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Serious adverse events will be assessed and recorded beginning after the first administration of 
study drug in the double-blind period of the study and ending at the time of study completion or 
ET of the double-blind period or the OLE period, whichever is later.  
If the SAE is related to a screening procedure, it will be captured from the date of informed 
consent.  
13.3 
Adverse Events of Special Interest  
Adverse events of special interest (AESI) for this study include:  
• 
Malignancies confirmed by histopathological report. Mast cells and eosinophils are part of 
the normal immune response. By decreasing their function, AK002 could theoretically 
increase the risk of malignancy. 
• 
Parasitic infections confirmed by positive clinical laboratory test. (Eosinophils are believed 
to be involved in protecting the body from parasitic infections. Decreasing their function 
could theoretically increase the risk of parasitic and opportunistic infections.) 
• 
Opportunistic infections (infections known to be more severe or occur more frequently in 
immunosuppressed populations) as confirmed by positive clinical laboratory test. 
• 
Infusion-related reactions and hypersensitivity reactions, including anaphylaxis. 
Adverse events of special interest will be assessed beginning after the time of the first infusion of 
study drug in the double-blind period of the study and ending at the time of study completion or 
ET of the double-blind period or the OLE period, whichever is later. Any new AESI or new 
information related to a previously reported AESI must be recorded in the AE eCRF and 
designated as an “AE of special interest.”  
13.4 
Infusion-Related Reactions 
All AE considered by the Investigator to be related to the infusion of the biological substance 
and occurring within 24 hours of the start of the study drug infusion should be captured as 1 AE, 
termed “IRR.” Common symptoms of IRR include but are not limited to:  
 


 
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• 
Flushing 
• 
Nausea 
• 
Chills 
• 
Vomiting 
• 
Back or abdominal pain 
• 
Sweating 
• 
Chest discomfort or tightness 
• 
Fever 
• 
Dizziness 
• 
Urticaria 
• 
Shortness of breath 
• 
Pruritus 
• 
Headache 
• 
Bronchospasm 
• 
Hypotension or hypertension 
 
All symptoms experienced by a patient during an IRR will be listed in the eCRF under 1 IRR, 
unless the Investigator believes a symptom is not part of the IRR, in which case it will be 
recorded separately. The start time of the IRR will be captured as the start time of the first 
symptom and the end time of the IRR will be captured as the end time of the last symptom.  
Any medications used within 24 hours of an infusion for the treatment of an IRR are not 
considered prohibited medications.  
13.5 
Anaphylaxis 
A suspicion of anaphylaxis will be carefully monitored and treated according to standard of care. 
Emergency crash cart equipment and medications, including multiple doses of epinephrine, 
vasopressors, and bronchodilators, will be available at all times during the conduct of the study.  
To define anaphylactic reactions in a consistent and objective manner, all AE of suspected 
anaphylaxis will be evaluated using Sampson’s Criteria for Anaphylaxis (Appendix 6). 
The assessment of an AE will be done pursuant to definitions set forth by ICH Good Clinical 
Practice (GCP) guidelines and applicable regulatory requirements.  
If a patient experiences signs or symptoms of anaphylaxis, they should be treated with standard 
of care, such as diphenhydramine, acetaminophen, methylprednisolone, epinephrine, and other 
supportive measures along with cessation of the infusion. 


 
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13.6 
Evaluating Adverse Events and Serious Adverse Events 
13.6.1 
Establishing Diagnosis 
Whenever possible, diagnoses should be given when signs and symptoms are due to a common 
etiology (e.g., dysuria, urinary nitrites should be reported as a urinary tract infection). If the 
diagnosis is not known, individual signs and symptoms should be assessed and recorded in the 
AE eCRF as separate AE. The Investigator (or qualified Subinvestigator) must assign the 
following AE attributes listed below and is responsible for ensuring this information is recorded 
in the source documentation. 
13.6.2 
Assessment of Intensity 
Investigators will use their clinical judgment as well as the guidelines laid out in the NCI 
CTCAE (version 5.0 or most current version) tables to assess the intensity of each AE and SAE 
(Table 3 and Appendix 4). 
Table 3 
Adverse Event Severity per CTCAE 
Grade 
CTCAE Description* 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate 
instrumental activities of daily living (ADL). 
3 
Severe or medically significant but not immediately life-threatening, hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL. 
4 
Life-threatening consequences, urgent intervention indicated. 
5 
Death related to AE. 
* CTCAE v. 5.0: Grade refers to the severity of the AE. The CTCAE displays Grades 1–5 with unique clinical 
descriptions of severity for each AE based on this general guideline. 
The term “severe” is a measure of intensity, and a severe AE is not necessarily a SAE.  
When the intensity of an AE changes more than once a day, the maximum severity for the event 
should be entered into the AE eCRF. If the intensity changes over a number of days, these 
changes should be recorded separately (i.e., as having distinct onset dates). 
13.6.3 
Assessment of Causality to Study Drug 
The Investigator should use their clinical judgment as well as the guidelines in Table 4 to assess 
the relationship between study drug and AE. 


 
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Table 4 
Adverse Event Relationship to Study Drug  
Relationship to 
Study Drug 
Comment 
Related 
There is clear evidence that the event is related to the use of study drug (e.g., confirmation by 
positive re-challenge test, if possible). Another etiology is considerably less likely. 
Possible 
The event cannot be explained by the subject’s medical condition, concomitant therapy, or 
other causes, and there is a plausible temporal relationship between the event and study drug 
administration.  
Unlikely/Remote 
An event for which an alternative explanation is more likely (e.g., concomitant medications 
or ongoing medical conditions) or the temporal relationship to study drug administration 
and/or exposure suggests that a causal relationship is unlikely. (For reporting purposes, 
Unlikely/Remote will be grouped together with Not Related.)  
Not Related 
The event can be readily explained by the subject’s underlying medical condition, 
concomitant therapy, or other causes, and therefore, the Investigator believes no relationship 
exists between the event and study drug.  
13.6.4 
Assessment of Causality to Study Procedure 
The Investigator should use their clinical judgment as well as the guidelines in Table 5 to assess 
the relationship between study procedure and AE. Assessment of Causality to Study Procedure 
should include causality to such items as EGD with biopsy or blood draw (as appropriate), or 
other.  
Table 5 
Adverse Event Relationship to Study Procedure 
Relationship to 
Study Procedure 
Comment 
Related 
There is clear evidence that the event is related to a study procedure. 
Possible 
The event cannot be explained by the subject’s medical condition, concomitant therapy, or 
other causes, and there is a plausible temporal relationship between the event and a study 
procedure.  
Unlikely/Remote 
An event for which an alternative explanation is more likely (e.g., concomitant medications 
or ongoing medical conditions) or the temporal relationship to any study procedure suggests 
that a causal relationship is unlikely (For reporting purposes, Unlikely/Remote will be 
grouped together with Not Related).  
Not Related 
The event can be readily explained by the subject’s underlying medical condition, 
concomitant therapy, or other causes, and therefore, the Investigator believes no relationship 
exists between the event and a study procedure.  


 
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13.6.5 
Action Taken 
Action taken with respect to study drug will be categorized as none, study drug permanently 
discontinued, study drug temporarily withdrawn, or other (specify). 
Action taken with respect to study participation will be categorized as none, withdrawal from 
study participation, or other (specify).  
Action taken with respect to treatment of an AE will be categorized as none, concomitant 
medication, concomitant procedure, or other (specify).  
13.6.6 
Assessment of Outcome 
Event outcome at resolution or time of last follow-up will be recorded as: recovered, recovering, 
not recovered, recovered with sequelae, fatal, or unknown.  
13.7 
Adverse Event Reporting Procedures  
13.7.1 
All Adverse Events  
Any clinically significant AE that is ongoing at the time of study completion or ET will be 
followed by the Investigator until event resolution, the AE is otherwise explained, not considered 
clinically significant by the Investigator, or the patient is lost to follow-up. 
All AE identified, whether serious or non-serious, will be recorded in the AE eCRF beginning 
after the time of first administration of study drug in the double-blind period of the study and 
ending at the time of study completion or ET of the double-blind period or the OLE period, 
whichever is later. Serious adverse events considered related to screening procedures will be 
recorded in the AE eCRF starting on the date of informed consent. Whenever appropriate, the 
CTCAE (version 5.0 or most current version) should be utilized for naming common AE 
(Appendix 4). 
13.7.2 
Serious Adverse Event Reporting  
In the event of any SAE reported or observed during the study, whether or not attributable to the 
study drug, site personnel must report it immediately (within 24 hours of becoming aware of 
the SAE) by telephone or email to the Sponsor, Allakos Inc.  
The SAE report forms will be provided to the investigational site to assist in collecting, 
organizing, and reporting SAE, and forms must be completed with as much information as is 
available and should be submitted to the Sponsor within 24 hours of becoming aware of the 
event. Serious adverse events must also be recorded on the AE eCRF and designated as 
“serious.”  


 
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Even when only minimal information is available for the initial SAE report, the Investigator 
should try to make a causality assessment, as the causality is used to determine the timing of 
regulatory reporting requirements. If the Investigator or designee is not available to sign the SAE 
report on initial submission, they should be contacted by telephone and their assessment 
documented on the SAE form (with a note stating signature is forthcoming). The Investigator 
may change their causality assessment based on follow-up information and submit an amended 
SAE report form.  
All efforts will be made to obtain accurate and complete medical records for the SAE. All efforts 
to obtain information should be documented in the patient source documents.  
The site will notify the IRB according to its guidelines.  
The patient’s condition will be followed by the Investigator or designated Subinvestigator until 
resolution of the condition or a return to baseline levels. If additional visits are required, the 
patient will be asked to return to the study site for further follow-up. If the condition is still 
ongoing at the time the patient exits the study, every effort will be made to continue to follow up 
with the patient for a reasonable period of time, as determined by the Investigator or until there is 
a return to baseline or stabilization of the condition. As additional information becomes 
available, such as hospital discharge notes and patient medical records, the Investigator will be 
notified and provided with all relevant information.  
All SAE that have not resolved by the end of the study or that have not resolved on 
discontinuation of the patient’s participation in the study must be followed until any of the 
following occurs:  
• 
The event resolves.  
• 
The event stabilizes. 
• 
The event returns to baseline if a baseline value is available.  
• 
The event can be attributed to agents other than the investigational product or to factors 
unrelated to study conduct.  
• 
It becomes unlikely that any additional information can be obtained (patient or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts).  


 
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Serious AE must be reported within 24 hours to:  
 
SAE Reporting 
Fax: 
+1-888-237-7475 
Email: 
SAE@allakos.com 
13.7.3 
Pregnancy Reporting 
Pregnancies are captured if they occur in female patients or in the sexual partners of male 
patients from the time the patient is first exposed to the investigational product through 
Day 225 (±3) or 84 (±3) days after last dose if patient does not enroll in the OLE period of the 
study, or until the start of the first dose in the OLE period of the study, unless otherwise directed 
by Allakos.  
Female patients must be instructed to discontinue all study drugs and inform the Investigator 
immediately if they become pregnant during the study. Male patients must be instructed to 
inform the Investigator immediately if their partner becomes pregnant during the study. 
The Investigator must report any pregnancy to Allakos within 24 hours of becoming aware of it 
using the provided pregnancy reporting forms. Female patients must be immediately 
discontinued from study drug. An uncomplicated pregnancy will not be considered an AE or 
SAE, but all pregnancies in patients who received AK002 will be followed through term.  
For male patients with female partners who become pregnant, the site will ask the father (the 
study subject) to provide information about the outcome of the pregnancy and information about 
the baby. If detailed health information about the mother is requested by Allakos, a Pregnant 
Partner Information Release Form will be provided to the site for the mother to sign. 
Any congenital abnormalities noted at birth in the offspring of a patient who received AK002 
will be reported as a SAE. If the patient received AK002, the outcome of any pregnancy and the 
presence or absence of any congenital abnormality will be recorded in the source documentation 
and reported to the Medical Monitor and Sponsor.  
13.7.4 
AESI Reporting 
Beginning from the time of first study drug infusion in the double-blind period of the study and 
ending at the time of study completion or ET of the double-blind period or the OLE period, 
whichever is later, unless otherwise directed by Allakos, any new AESI or new information 
related to a previously reported AESI must be recorded in the AE eCRF and designated as an 
“AE of special interest.”  


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 9 3 of 1 4 0 
C o nfi de nti al  
F or patie nts partici 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 2 1 d o u ble- bli n d tr eat me nt peri o d data base u p u ntil t he start of t he first o pe n-la bel 
i nf usi o n after t he Da y 1 7 6 visit a n d r ec or de d i n t he C R F of t he A K 0 0 2 -0 2 1 O L E peri o d data base 
b e gi n ni n g fr o m t he start of t he first o pe n -la bel i nf usi o n after t he Da y 1 7 6 visit. 
A n A E SI t hat als o q ualifies as a S A E ( per Secti o n 1 3. 2 ) m ust als o be re p orte d as a S A E i n 
acc or da nce wit h Secti o n 1 3. 7. 2 . A d verse e ve nts of s pecial i nterest t hat are als o S A E m ust be 
r ec or de 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 r e 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 war e ness.  
1 3. 8  
Me dic al M o nit ori n g  
Dr. 
 s h o ul d be c o ntacte d directl y usi n g t he p h o ne n u m ber a n d/ or e mail 
a d dr ess bel o w t o r e p ort me dical c o ncer ns or f or q uesti o ns re gar di n g safet y.  
All a k os A K 0 0 2- 0 2 1 Me dic al M o nit or  
All a k os A K 0 0 2 -0 2 1 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:  
 
1 3. 9  
I n de pe n de nt D at a M o nit ori n g C o m mittee 
A n I n de pe n de nt Data M o nit ori n g C o m mittee (i D M C) has bee n c o n ve ne d 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 safet y re vie ws.  
1 3. 1 0  St u d y Wit h dr a w al Crit eri a  
Partici pati o n of a patie nt will be disc o nti n ue d i n t he e ve nt t hat:  
•  
Occ urr e nce of a n e xcl usi o n criteri o n, w hic h is cli nicall y rele va nt a n d affects t he patie nt’s 
saf et y, if disc o nti n uati o n is c o nsi dere d necessar y b y t he I n vesti gat or a n d/ or S p o ns or. 
•  
Re b o u n di n g of e osi n o p hil c o u nts t o > 1 5 0 0/ µ L i n patie nts w h o e ntere d t he st u d y wit h 
e osi n o p hil le vels > 1 5 0 0/ µ L, a n d w h ose 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 will be wit h dr a w n fr o m t he st u d y at t he i nstr ucti o n of t he Safet y M o nit or. 
•  
Ser u m tr a nsa mi nases ( A L T a n d/ or A S T) > 3 × U L N a n d t otal bilir u bi n > 2 × U L N 
( c o nfir me d b y s u bse q ue nt r e peat) wit h o ut a n alter nati ve e x pla nati o n.  
•  
Ele vati o n of A L T or A S T > 3 × U L N (c o nfir me d b y re peat) wit h t he a p peara nce or 
w orse ni n g of s y m pt o ms  f elt b y t he I n vesti gat or t o be p ote ntiall y relate d t o he patic 
i nfla m mati o n, s uc h as f ati 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 ness, 
f e ver, r as h. 
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
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13.11 Study Stopping Rules 
The study may be discontinued prematurely in the event of any of the following: 
• 
A life-threatening AE that is possibly or probably related to treatment.  
• 
A fatal AE that is possibly or probably related to treatment.  
• 
New information leading to unfavorable risk-benefit judgment of the study drug. 
• 
Sponsor’s decision that continuation of the trial is unjustifiable for medical or ethical 
reasons.  
• 
Discontinuation of development of the Sponsor’s study drug.  
Health Authorities and IRB will be informed about the discontinuation of the study in 
accordance with applicable regulations. The study may be terminated or suspended on request of 
Health Authorities or Sponsor.  
14. Discontinuation and Replacement of Patients 
14.1 
Definition of Study Completion 
A patient who completes visits through the Day 225 (±3) visit will be recorded as having 
completed the double-blind period of the study. 
A patient who completes visits through the Day 176 (±3) visit and enters into the OLE period of 
the study will be categorized as having completed the double-blind period of the study. 
A patient who completes visits through OLE Day 197 (Day 372) (±3) visit will be recorded as 
having completed the OLE period of the study. 
14.2 
Early Discontinuation of Study Drug  
A patient may be discontinued from study treatment at any time if the patient, the Investigator, or 
the Sponsor feels that it is not in the patient’s best interest to continue. The following is a list of 
possible reasons for study treatment discontinuation: 
• 
Patient withdraws consent.  
• 
An AE that, in the opinion of the Investigator, results in it being in the best interest of the 
patient to discontinue study treatment.  
• 
Protocol deviation requiring discontinuation of study treatment.  
• 
Participation in any other study during the duration of this study.  


 
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• 
Use of a non-permitted concomitant drug which may adversely affect data interpretation in 
the opinion of the Medical Monitor. 
• 
Loss of ability to freely provide consent through imprisonment or involuntary incarceration 
or treatment of either a psychiatric or physical (e.g., infectious disease) illness.  
If a patient is withdrawn from treatment due to an AE, the patient will be followed and treated by 
the Investigator until the abnormal parameter or symptom has resolved or stabilized.  
All patients who discontinue study drug treatment should be encouraged to continue on study 
and complete assessments and procedures according to the 12-week follow-up period in Table 2, 
if possible (including follow-up EGD with colonoscopy).  
Reasonable attempts will be made by the Investigator to provide reasons for patient withdrawals. 
The reason for the patient’s withdrawal from the study or all attempts to acquire such, will be 
specified in the source documents.  
15. Statistical Methods and General Considerations 
This section outlines the statistical methods to be used for the analysis of the data from the study. 
A separate Statistical Analysis Plan (SAP), which must be documented as completed prior to 
unblinding the study, will describe data handling and statistical techniques in full detail and will 
supersede the statistical methods detailed in the protocol. The SAP will detail any modifications 
to the analysis plan described below.  
Unless specified otherwise, baseline will be defined as the last 2 weeks of observation before the 
first intravenous infusion of the study drug. All patient data will be listed. When appropriate, 
summary statistics of number of non-missing values, mean, median, standard deviation, 
minimum, and maximum will be computed for continuous variables, and summary statistics of 
number and proportion will be computed for categorical variables. Two-sided 95% confidence 
intervals will be provided for the mean and proportion. No formal statistical inferences will be 
made for safety parameters.  
15.1 
Sample Size 
A total of approximately 80 patients will be enrolled.  
First Co-Primary Endpoint: A sample size of 40 patients per treatment group will have >90% 
power to demonstrate a greater proportion of histologic responders at Week 24 in AK002 
patients when compared to placebo patients, assuming the proportions of histologic responders 
are 0.6 and 0.1 in the AK002 and placebo groups, respectively.  


 
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Second Co-Primary Endpoint: A sample size of 40 patients per treatment group will provide 
80% power to detect a statistically significant difference of 7.4 points between AK002 and 
placebo in the mean reduction from baseline in TSS at Weeks 23–24, assuming a common 
standard deviation of 12.5 points(AK002-003 data on file). 
15.2 
Analysis Populations 
The Safety population is defined as all patients who are randomized and have received at least 
1 infusion of the study drug. 
The primary efficacy analysis population is the Evaluable population defined as all randomized 
patients who have received at least 1 infusion of the study drug and at study entry do not meet 
any of the following criteria: 
1) 
>6 eosinophils/hpf in at least 1 esophageal biopsy at baseline. 
2) 
Documented history of irritable bowel syndrome and baseline diarrhea intensity ≥3. 
The complement to the Evaluable population will be referred to as the Excluded population. The 
Per Protocol (PP) population, defined as Evaluable population patients who have received at 
least 1 infusion of study drug and did not have significant protocol violations possibly interfering 
with assessment of efficacy. The Evaluable and Excluded populations will be used for all 
efficacy analysis. The PP population will be used for the primary endpoints and select secondary 
endpoint analyses. The Safety population will be used for all safety analysis. 
The study statistician along with the study team will review protocol deviations to identify 
patients to be excluded from the PP analysis population.  
15.3 
Patient Disposition 
Patient disposition and reason for early discontinuation will be tabulated. Patient demographics, 
baseline characteristics, and treatment exposure will be summarized. 
15.4 
Demographic and Baseline Characteristics 
The following demographic and baseline variables will be summarized: 
• 
Demographics 
• 
Medical history 
• 
Complete physical exam 
• 
ECG at screening 
• 
Screening vital signs and laboratory tests 


 
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Additionally, subgroup analysis will be conducted for the demographic variables (gender, race 
and age) and baseline disease characteristics (IgE <45 vs ≥ 45). 
15.5 
Study Drug Exposure 
Number and percent (n and %) of subjects who have received 1, 2, 3, 4, 5, or 6 infusions will be 
presented. 
15.6 
Efficacy Analysis 
15.6.1 
Primary Efficacy Endpoint Analysis 
The first co-primary endpoint will be analyzed using Fisher’s exact test. Patients who experience 
an ICE, i.e., exit the study prematurely or initiate prohibited or restricted medication, prior to end 
of Week 24 will be treated as non-responders. Proportion of responders and the associated 95% 
confidence interval (CI) will be presented for each treatment group. The between-group 
difference and the associated 95% CI will also be computed and presented. Sensitivity analysis 
may be carried out using the Cochran-Mantel-Haenszel (CMH) test stratified by the 
randomization stratification factor (baseline TSS <28 vs ≥28) to assess robustness of Fisher’s 
exact test results. 
The rationale for specifying Fisher’s exact test for the primary analysis as opposed to specifying 
the CMH test is because when a stratum has 100% response for 1 treatment group and 0% 
response for another treatment group, the CMH test may lose efficiency or not be computable. 
This is evident from the Phase 2 study outcome.  
The second co-primary endpoint will be analyzed using mixed model for repeat measures 
(MMRM) with treatment, week, treatment-by-week interaction, and baseline TSS-by-week 
interaction as fixed factors; gender and baseline TSS (continuous) as covariates; and study site 
(with pooling by geographic location) as random effect. If the model does not converge with 
pooled sites as a random effect, it will be simplified with pooled site as a fixed effect. Details 
about the method for pooling sites will be provided in the statistical analysis plan (SAP).  
The weekly TSS is calculated as the average of the daily TSS. Weekly TSS will be set to missing 
if >3 daily TSS are missing. Baseline TSS will be the average of the last 2 weeks of daily TSS 
collected prior to the first infusion. The model variance-covariance matrix will be unstructured. 
However, if computation does not converge, the matrix will take the form of Toeplitz, 
autoregressive, or compound symmetry, whichever converges first. 
Data on patients who experience an ICE, i.e., exit the study prematurely or initiate prohibited or 
restricted medications, prior to the end of Week 24 will be set to missing. If it is evident that the 


 
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second co-primary endpoint is confounded by the influence of background variables, then the 
second co-primary analysis will be conducted adjusting for the effects of the background 
variables. Possible confounding factors may include age, presence of esophageal inflammation, 
history of IBS, and presence of diarrhea at baseline. 
Two sensitivity analyses are planned. The first is a pattern-mixture model, where it will be 
assumed that AK002 patients who experience an ICE will have a trajectory comparable to 
placebo post-ICE. This analysis will therefore provide a stress test of the missing at random 
(MAR) assumption of the MMRM employed in the principal analysis and will provide a 
conservative estimate of the treatment effect. The pattern-mixture model will be implemented 
using multiple imputations, and the inference of this sensitivity analysis will be based on the 
combined estimates using the standard multiple imputation technique. The imputed data sets will 
be analyzed with the same MMRM model utilized in the primary analysis and then summarized 
using PROC MIANALZE. The other is to analyze the average of Week 23 through Week 24 
using ANCOVA with treatment and study site as factors, gender and baseline TSS (continuous) 
as covariates. Missing Week 23 through Week 24 weekly TSS will be imputed prior to 
ANCOVA using SAS PROC MI under the MAR assumption. 
Detailed specifications for the missing data imputation will be provided in the SAP.  
15.6.2 
Secondary Efficacy Endpoint Analysis 
If both tests of the co-primary endpoints are statistically significant, the hypothesis tests for the 
secondary endpoints will proceed sequentially in a prespecified order (see Section 4.2). If at any 
point, the statistical test is not significant at 2-sided α=0.05 level, the hypothesis testing 
procedure will stop. All endpoints prior to this point will be considered statistically significant, 
and inferential statistics after this point will be considered descriptive.  
For tissue eosinophil count, the calculation will be based on the average count of the highest 
readings from the mucosa at baseline and Day 169 (Week 24). The change in tissue eosinophil 
count from baseline to Day 169 will be analyzed using ANCOVA with treatment, study site 
(with pooling by geographic location) as factors, and baseline eosinophil counts, gender, and 
baseline PRO TSS as covariates. Least square means (LSM), standard errors (SE), and 95% CI 
for individual treatment groups and LSM, SE, 95% CI, and p-value for the between-treatment 
difference will be presented. 
Proportion of patients achieving mean eosinophil count of ≤1 cell/hpf in 3 highest duodenal hpf 
at Week 24 will be analyzed using Fisher’s exact test like the analysis for the first co-primary 
endpoint. 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 9 9 of 1 4 0 
C o nfi de nti al  
Pr o p orti o n of tr eat me nt r es p o n ders at Wee ks 2 3 – 2 4 , w here a res p o n der is defi ne d as > 3 0 % 
i m pr o ve me nt i n T S S a n d mea n e osi n o p hil c o u nt ≤1 5 cells/ h pf i n 3 hi g hest d u o de nal h pf , will be 
a nal yze d usi n g Fis her’s e xact test  li ke t he a nal ysis f or t he first c o-pri mar y e n d p oi nt . 
Pr o p orti o n of patie nts wit h ≥5 0 % r e d ucti o n a n d ≥7 0 % re d ucti o n i n T S S fr o m baseli ne t o 
Wee ks  2 3 –2 4 will be a nal yze d usi n g Fis her’s e xact test, a n d se nsiti vit y a nal ysis will be 
c o n d ucte d usi n g t he C M H test str atifie d b y t he ra n d o mizati o n stratificati o n fact ors.  
C ha n ge i n wee kl y T S S will be a nal yze d usi n g t he  M M R M m o del . T he m o del will i ncl u de fi xe d 
eff ects f or baseli ne val ue, tr eat me nt, wee k , treat me nt b y wee k i nteracti o n, baseli ne val ue b y 
wee k i nter acti o n, a n d all o w f or r a n d o m s u bject effects . T he m o del varia nce -c o varia nce matri x 
will be u nstr uct ur e d. H o we ver, if c o m p utati o n d oes n ot c o n ver ge, t he matri x will ta ke t he f or m 
of T oe plitz, A R( 1), a n d c o m p o u n d s y m metr y, w hic he ver c o n ver ges first . 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 . L S M  a n d t he 9 5 % CI f or 
t he bet wee n-gr o u p diff er e nce will be esti mate d f or eac h wee k. T he e m pirical c u m ulati ve 
distri b uti o n f u ncti o n  (e C D F ) a n d pr o ba bilit y distri b uti o n f u ncti o n  (P D F ) pl ots will be prese nte d 
f or c ha n ge fr o m baseli ne T S S at Wee ks 2 3 – 2 4. 
1 5. 6. 3  E x pl or at or y A n al ysis  
C ha n ge fr o m baseli ne 
 at Wee k 2 5 will be a nal yze d usi n g 
t he 
 si milar t o t he a nal ysis o utli ne d a b o ve.  
C ha n ge i n 
 
 
 as a p plica ble, fr o m baseli ne c o m pare d t o p ost-treat me nt will be a nal yze d usi n g t he 
 C ha n ges i n 
 fr o m baseli ne c o m pare d t o p ost-treat me nt i n t he 
 will be a nal yze d usi n g t he 
 
C ha n ge fr o m baseli ne i n t he 
 will be s u m marize d b y 
 f or 
eac h of t he f oll o wi n g 
: 
•  
 
•  
 
•  
 
•  
 
•  
 
•  
 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 0 0 of 1 4 0 
C o nfi de nti al  
All 
 will be a nal yze d usi n g t he 
 as descri be d 
a b o ve. 
 a n d t he 
 f or t he bet wee n-gr o u p c o m paris o n will  be 
pr ese nte d f or t he 
 acr oss Wee k 1 t hr o u g h Wee k 2 4 a n d f or t he  
 at eac h wee k.  
•  
, t he a nal ysis varia ble, will be base d o n t he 
 
 
 t o esta blis h a 
 
•  
 t he a nal ysis varia ble, will be t he 
 
( defi ne d as 
 a n d calc ulate d as t he  
 
 
 t o esta blis h a 
.  
T he y will t he n be a nal yze d usi n g t he 
 
1 5. 7  
S af et 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 dical Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A) a n d will be classifie d b y Me d D R A s yste m or ga n class ( S O C) a n d preferre d ter m. 
Listi n gs will i ncl u de all A E c ollecte d o n st u d y. T he s u m maries of A E will be base d o n T E A E, 
defi ne d as a n A E r e 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 i ntr a ve n o us i nf usi o n of t he st u d y me dicati o n.  
1 5. 7. 1  
Tre at m e nt E m er ge nt A d verse E ve nts  
Patie nt i nci de nce ( N a n d %) of T E A E will be s u m marize d as f oll o ws:  
•  
O ver vie w of T E A E t o i ncl u de  
− N u m ber ( %) of patie nts w h o re p orte d at least 1 T E A E o verall, b y se verit y, a n d b y 
r elati o ns hi p 
− N u m ber ( %) of patie nts w h o re p orte d at least 1 seri o us T E A E  
− N u m ber ( %) of patie nts w h o re p orte d at least 1 T E A E lea di n g t o treat me nt 
disc o nti n uati o n  
− N u m ber ( %) of patie nts w h o r e p orte d at least 1 T E A E of s pecial i nterest ( T E A E SI)  
•  
T E A E b y pr ef err e d ter m  
•  
T E A E b y S O C a n d pr ef err e 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 ter m  
•  
T E A E b y S O C a n d pr ef err e d ter m a n d relati o ns hi p t o st u d y dr u g  
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


 
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• 
TEAE leading to withdrawal by SOC and preferred term  
• 
Serious TEAE by SOC and preferred term  
• 
TEAESI by SOC and preferred term 
15.7.2 
Anti-Drug Antibodies 
Samples will be obtained for testing of ADA at times identified in Section 11.5.4.  
15.7.3 
Clinical Laboratory Assessments 
Samples will be obtained for the clinical laboratory tests identified in Section 11.4, and 
laboratory tests to be summarized include chemistry, hematology, urinalysis, and AK002 ADA. 
Descriptive statistics will be used to summarize laboratory results at baseline, each visit, and the 
change from baseline for each visit. In addition, shift tables will summarize the laboratory results 
relative to normal reference ranges at baseline and each post-baseline time point.  
15.7.4 
Vital Signs 
Vital signs will be summarized at baseline, each visit, and change from baseline at each visit.  
15.7.5 
ECG 
Patient incidence of the Investigator’s overall assessment (normal, abnormal – not clinically 
significant, and abnormal – clinically significant) will be summarized. 
15.7.6 
Physical Exam 
New or worsening symptoms in the symptom-directed physical exams will be included in the 
by-patient data listing.  
15.7.7 
Concomitant Medications 
All medications (prior and concomitant) will be coded using the most current World Health 
Organization Drug Dictionary (WHODD). Concomitant medications will be summarized by 
Anatomical Therapeutic Chemical (ATC) Class and preferred term.  
15.8 
Patient Confidentiality 
Patient identity should be confirmed, if possible, by the presentation of a photo identification to 
ensure the correct individual is consented, screened, and enrolled (if eligible). Only the PID, 
patient initials, and demographics will be recorded in the eCRF. If the patient’s name appears on 
any source document collected (e.g., hospital discharge summary), it must be removed from the 
document if the document will be viewed by the Sponsor or a sponsor-contracted study vendor 
not permitted access to patient-identifying information. All study findings will be stored in 


 
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electronic databases. The patients will give explicit written permission for representatives of the 
Sponsor, regulatory authorities, and the IRB to inspect their medical records to verify the 
information collected. Patients will be informed that all personal information made available for 
inspection will be kept confidential to the extent permitted by all applicable state, local, and 
federal data protection/privacy laws and/or regulations and will not be made publicly available. 
If the results of the study are published, the patient’s identity will remain confidential. At study 
check-in to the study site, patients will be advised not to share their study information with other 
patients or on social media. 
16. Data Collection, Retention, and Monitoring  
16.1 
Data Collection Instruments  
All staff at participating clinical sites will adhere to good documentation practices. Data will be 
entered into the eCRF using source document data. Source documents may include but are not 
limited to laboratory data, recorded data from automated instruments, medical progress notes, 
and email correspondence.  
16.2 
Data Management Procedures  
The data will be entered into a validated database. The data management group will be 
responsible for data processing in accordance with procedural documentation. Database lock will 
occur once quality assurance procedures have been completed. All procedures for handling and 
analysis of data will be conducted using good computing practices meeting Food and Drug 
Administration (FDA) guidelines for handling and analysis of data for clinical trials.  
16.3 
Data Quality Control and Reporting  
After data have been entered into the study database, a system of computerized data validation 
checks will be implemented and applied to the database on a regular basis. Queries are entered, 
tracked, and resolved through the electronic data capture system directly. The study database will 
be updated in accordance with the resolved queries. All changes to the study database will be 
documented.  
16.4 
Database Lock/Disclosure of Randomization Code 
The database lock will occur after all subjects complete participation in the double-blind period 
of the study. For the database lock, applicable EDC data will be locked in order 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. 
16.5 
Archiving of Data 
The database is safeguarded against unauthorized access by established security procedures; 
appropriate backup copies of the database and related software files will be maintained. 
Databases are backed up by the database administrator in conjunction with any updates or 
changes to the database.  
At critical junctures of the protocol (e.g., production of interim reports and final reports), data for 
analysis is locked and cleaned per established procedures.  
16.6 
Availability and Retention of Investigational Records 
In accordance with 21 CFR 312.62(c), GCP, and all other applicable regulatory requirements, 
following completion or termination of the study, the Sponsor or its designee will retain a copy 
of all study records in a limited access storage room for a minimum of 2 years after notification 
that the investigations have been discontinued and the FDA has been notified, or for 2 years after 
all marketing applications have been approved. The trial master file will be created during the 
implementation phase of a study, maintained on an ongoing basis throughout the duration of the 
project, and collated at the end of the study. The files will contain folders that may include but 
are not limited to the following subcategories: 
• 
Financial agreements 
• 
Regulatory documents 
• 
Independent Ethics Committee (IEC)/IRB Documents 
• 
Drug Accountability 


 
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• 
Correspondence 
• 
Medical Reports 
• 
Patient Data 
• 
Monitoring Visit Reports 
• 
Sample CRF and CRF Guidelines 
16.7 
Monitoring 
Monitoring visits will be conducted by representatives of the Sponsor according to 21 CFR 
Parts 50, 56, and 312 and ICH GCP Guideline E6. By signing this protocol, the Investigator 
grants permission to the Sponsor (or designee) and appropriate regulatory authorities to conduct 
on-site monitoring and/or auditing of all appropriate study documentation. As necessitated by the 
COVID-19 pandemic, monitoring of all appropriate study documentation may occur off-site, 
with remote access to study documents, as permitted by individual study site requirements.  
17. Administrative, Ethical, and Regulatory Considerations 
The study will be conducted in a manner consistent with the Declaration of Helsinki, Protection 
of Human Volunteers (21 CFR 50), IRB (21 CFR 56 and ICH E6), and Obligations of Clinical 
Investigators (21 CFR 312 and ICH E6). The Investigator must also comply with all applicable 
privacy regulations (e.g., HIPAA, European Union Data Protection Directive 95/46/EC).  
17.1 
Protocol Amendments  
An amendment must be agreed to in writing by Allakos Inc. and submitted to the health authority 
as a Clinical Trial Application/Investigational New Drug (IND) amendment. Protocol 
amendments cannot be implemented without prior written IRB approval except as necessary to 
eliminate immediate safety hazards to patients. Written approval of a protocol amendment is not 
required prior to implementation of changes to the protocol that eliminate immediate hazard to 
the patient; however, approval must be obtained as soon as possible thereafter. Each protocol 
amendment must also be signed by the Investigator.  
17.2 
Independent Ethics Committees/Institutional Review Boards 
The protocol and ICF will be reviewed and approved by the IEC/IRB of each participating study 
site prior to study initiation. A Central IRB may be used if permitted by the participating study 
site. All SAE, regardless of causality, will be reported to the IRB in accordance with the SOP 
and policies of the IRB, and the Investigator will keep the IRB informed as to the progress of the 
study. The Investigator will obtain assurance of IRB compliance with regulations.  


 
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Any documents that the IRB may need to fulfill its responsibilities (such as protocol, protocol 
amendments, Investigator’s Brochure, ICF, information concerning patient recruitment, payment 
or compensation procedures, or other pertinent information) will be submitted to the IRB. The 
IRB’s written unconditional approval of the study protocol and the ICF will be in the possession 
of the Investigator before the study is initiated. The IRB’s approval of the investigational site 
must be available to Allakos prior to shipment of study supplies to the site. This approval must 
refer to the study by exact protocol title and number and should identify the documents reviewed 
and the date of review.  
The IRB must be informed of revisions to other documents originally submitted for review; 
serious and/or unexpected adverse experiences occurring during the study in accordance with the 
SOP and policies of the IRB; new information that may adversely affect the safety of subjects or 
the conduct of the study; an annual update and/or request for reapproval; and when the study has 
been completed.  
17.3 
Informed Consent Form 
Prior to study enrollment, all patients must consent to participate. The process of obtaining the 
informed consent will comply with all federal regulations, ICH requirements, and local laws.  
In accordance with ICH GCP Guideline E6 Section 4.3.3, patients should be asked whether they 
would like their primary care physician notified of their study participation. If yes, the primary 
care physician should be notified in writing. Otherwise, the patient should sign a form stating 
that he/she does not wish to disclose such information.  
The Investigator or designee will review the study and the ICF with each potential patient. The 
review will include the nature, scope, procedures, and possible consequences of participation in 
the study. The consent and review must be in a form understandable to the potential patient. The 
Investigator or designee and the subject must both sign and date the ICF after review and before 
the patient can participate in the study. The patient will receive a copy of the signed and dated 
form, and the original will be retained in the site’s study files. The Investigator or designee must 
emphasize to the patient that study participation is entirely voluntary and that consent regarding 
study participation may be withdrawn at any time without penalty or loss of benefits to which the 
patient is otherwise entitled.  
In addition, prior to undergoing biopsies, patients will provide informed consent in accordance 
with the SOP and policies of the EGD facility/investigational site.  


 
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17.4 
Publications 
The preparation and submittal for publication of manuscripts containing the study results will be 
in accordance with a process determined by mutual written agreement among the study Sponsor 
and respective site. The publication or presentation of any study results will comply with all 
applicable privacy laws including but not limited to the Health Insurance Portability and 
Accountability Act of 1996.  
17.5 
Clinical Trial Registration 
This clinical study is registered on the Clinical Trial Registry Website, www.ClinicalTrials.gov, 
as NCT #04856891. 
17.6 
Payment to Patients 
All patients may be compensated for participating in this study, in accordance with the payment 
amounts per study day stated in the patient’s signed ICF approved by the IRB. If the patient is 
discontinued from the study prior to the last study visit, the patient will be compensated for each 
completed study visit on a pro rata basis, as stated in the patient’s ICF. Beginning at dosing 
Day 1, Patients will be compensated for each completed week of daily questionnaires as long as 
at least 4 questionnaires per week are completed. After randomization, patients at participating 
study sites may be reimbursed for expenses associated with attending study visits. No additional 
compensation beyond what is stated in the ICF is permitted.  
17.7 
Investigator Responsibilities  
By signing the Investigator Protocol Agreement page, the Investigator agrees to:  
1) 
Conduct the study in accordance with the protocol and only make changes after notifying 
the Sponsor (or designee), except when to protect the safety, rights, or welfare of subjects.  
2) 
Personally conduct or supervise the study. 
3) 
Ensure that the requirements relating to obtaining informed consent and IRB review and 
approval meet federal guidelines.  
4) 
Report to the Sponsor or designee any AE that occur in the course of the study, in 
accordance with 21 CFR Part 312.64 and ICH Guideline E2A.  
5) 
Ensure that all associates, colleagues, and employees assisting in the conduct of the study 
are informed about their obligations in meeting the above commitments.  
6) 
Maintain adequate and accurate records in accordance with 21 CFR Part 312.62 and ICH 
Guideline E6 and to make those records available for inspection with the Sponsor (or 
designee).  


 
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7) 
Ensure that an IRB that complies with the requirements of 21 CFR Part 56 and ICH 
Guideline E6 will be responsible for initial and continuing review and approval of the 
clinical study.  
8) 
Promptly report to the IRB and the Sponsor (or designee) all changes in the research 
activity and all unanticipated problems involving risks to patients or others (to include 
amendments and IND safety reports).  
9) 
Seek IRB approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the patients. 
10) Comply with all other requirements regarding the obligations of clinical Investigators and 
all other pertinent requirements listed in 21 CFR Part 312.  


 
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18. References  
Alhmoud T, Hanson J, Parasher G. Eosinophilic gastroenteritis: an underdiagnosed condition. 
Dig Dis Sci, 2016;61:2585–92. 
Allakos Clinical Study Report AK002-003. A Phase 2, multicenter, randomized, double-blind, 
placebo-controlled study to evaluate the efficacy, safety, tolerability, and 
pharmacodynamic effect of AK002 in patients with eosinophilic gastritis and/or 
eosinophilic gastroenteritis, version 1, 18 June 2021. 
Allakos Clinical Study AK002-019. A prospective study to identify the incidence of eosinophilic 
gastrointestinal diseases and elevated tissue mast cells among patients with chronic 
gastrointestinal symptoms. Data on file, 2021. 
Bedell A, Taft T, Craven M, Guadagnoli L, Hirano I, Gonsalves N. Impact on health-related 
quality of life in adults with eosinophilic gastritis and gastroenteritis: A qualitative 
assessment. Dig Dis Sci, 2018;63:1148–57. 
Bochner B. Siglec-8 on human eosinophils and mast cells, and Siglec-F on murine eosinophils, 
are functionally related inhibitory receptors. Clin Exp Allergy 2009;39(3):317-24. 
Caldwell J, Collins M, Stucke E, Putnam P, Franciosi J, Kushner J, et al. Histologic eosinophilic 
gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 
immunity, and a unique gastric transcriptome. J Allergy Clin Immunol 2014; 
134:1114-24. 
Dellon E, Peterson K, Murray J, Falk G, Gonsalves N, Chehade M, et al. Anti-Siglec-8 antibody 
for eosinophilic gastritis and duodenitis. N Engl J Med, 2020;383:1624–34. 
Food and Drug Administration. Birth Control Chart from FDA.gov/consumers/free-publications-
women/birth-control. FDA.gov/consumers/free-publications-women/birth-control, 
21 Jun 2021, retrieved 27 Feb 2022, from https://www.fda.gov/consumers/free-
publications-women/birth-control. 
Food and Drug Administration. Guidance for industry ICH E9 (R1) statistical principles for 
clinical trials addendum: estimands and sensitivity analysis in clinical trials. CDER, 
May 2021.  
Hudson S, Herrmann H, Du J, Cox P, Haddad el B, Butler B, et al. Developmental, malignancy-
related, and cross-species analysis of eosinophil, mast cell, and basophil siglec-8 
expression. J Clin Immunol, 2011;31:1045–53. 


 
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Jensen E, Martin C, Kappelman M, Dellon E. Prevalence of eosinophilic gastritis, gastroenteritis, 
and colitis: Estimates from a national administrative database. J Pediatr Gastroenterol 
Nutr, 2016;62:36–42. 
Katz P, Gerson L, Vela M. Guidelines for the diagnosis and management of gastroesophageal 
reflux disease. Am J Gastroenterol, 2013;108:308–328. 
Licari A, Votto M, Scudeller L, De Silvestri A, Rebuffi C, Cianferoni A, Marseglia G. 
Epidemiology of nonesophageal gastrointestinal diseases in symptomatic patients: A 
systematic review and meta-analysis. J Allergy Clin Immunol Pract, 2020;8:1994–2003. 
López-Medina G, Gallo M, Prado A, Vicuna-Honorato I, Díaz de León R. Eosinophilic 
gastroenteritis: case report and review in search for diagnostic key points. Case Rep 
Gastrointest Medicine, 2015; 239506:1–5. 
Mansoor E, Saleh M, Cooper G. Prevalence of eosinophilic gastroenteritis and colitis in a 
population-based study, from 2012-2017. Clin Gastroenterol Hepatol, 2017; 15:1733-41. 
Peterson K, Byrne K, Vinson L, et al. Elemental diet induces histologic response in eosinophilic 
esophagitis. Am J Gastroenterol, 2013;108:759–66. 
Prussin C. Eosinophilic gastroenteritis and related eosinophilic disorders. Gastroenterol Clin 
North Am 2014; 43: 317-27. 
Reed C, Woosley J, Dellon E. Clinical characteristics, treatment outcomes and resource 
utilization in children and adults with eosinophilic gastroenteritis. Dig Liver Dis 2015; 
47: 197-201. 
Sampson H, Munoz-Furlong A, Campbell R, Adkinson Jr N, Bock S, Branum A, et al. Second 
symposium on the definition and management of anaphylaxis: summary report--Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network symposium. J Allergy Clin Immunol 2006;117(2):391–7. 
Wechsler J, Schwartz S, Amsden K, Kagalwalla A. Elimination diets in the management of 
eosinophilic esophagitis. J Asthma Allergy, 2014;7:85–94. 
Zhang M, Li Y. Eosinophilic gastroenteritis: A state-of-the-art review. J Gastroenterol Hepatol 
2017; 32: 64-72.  
 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 1 0 of 1 4 0 
C o nfi de nti al  
1 9.  A p pe n dices  
1 9. 1 
A p pe n di x 1:  P R O Q uesti o n naire  
1 9. 2 
A p pe n di x 2:  
 
1 9. 3 
A p pe n di x 3:  Baseli ne Diet Assess me nt  
1 9. 4 
A p pe n di x 4:  C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts v. 5. 0  
1 9. 5 
A p pe n di x 5:  E G D a n d C ol o n osc o p y Hist ol o g y  
1 9. 6 
A p pe n di x 6:  Sa m ps o n’s Criteria of A na p h yla xis  
1 9. 7 
A p pe n di x 7:  e P R O T eac hi n g T o ol f or St u d y A K 0 0 2 - 0 2 1 
1 9. 8 
A p pe n di x 8:  
  
1 9. 9 
A p pe n di x 9:  
  
1 9. 1 0 A p pe n di x 1 0:  A d diti o nal Q uesti o ns f or D ys p ha gia a n d C o nsti pati o n   
1 9. 1 1 A p pe n di x 1 1:  Pr e vi o us Tr eat me nts  a n d Pr oce d ure  Re vie w   
1 9. 1 2 A p pe n di x 1 2:  He patitis B a n d He patitis C Ser ol o gic T esti n g Details   
1 9. 1 4 A p pe n di x 1 3: O pe n -L a bel E xte nsi o n Peri o d – O pti o nal   
 
C CI
C CI
C CI


 
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19.1 
Appendix 1: PRO Questionnaire  
 
 


 
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19.1 
Appendix 1: PRO Questionnaire cont. 
 


 
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19.1 
Appendix 1: PRO Questionnaire cont. 
 
Bristol Stool Form Scale (English for United States) 
 
BSFS – United States/English – Original version. BSFS_AU1.2_eng-USori.doc 
Copyright 2000 © by Rome Foundation. All Rights Reserved. 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 1 4 of 1 4 0 
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 1 5 of 1 4 0 
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 1 6 of 1 4 0 
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 1 7 of 1 4 0 
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 1 8 of 1 4 0 
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 1 9 of 1 4 0 
C o nfi de nti al  
 
C CI
C CI


 
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19.3 
Appendix 3: Baseline Diet Assessment  
Instructions: To be completed by Study Personnel, through direct interview with Study Participant. Please ask 
questions to Study Participants, much as they appear below. This assessment should be conducted on Day 1 of 
screening. This assessment asks about symptoms of eosinophilic duodenitis (EoD). 
1. 
Are you on Specific, Doctor-Prescribed Diet? 
Yes ☐ 
No ☐ 
 
If Yes, what is the diet? 
 
☐ Elemental 
[If ticked-enteral/tube feeding?]  
Yes ☐  
No ☐ 
 
☐ 6-food or 3 Food Elimination Diet 
 
☐ Supplemental Protein Shake/drink  specify:  
 
 
☐ Other; describe:  
 
2. 
Do you have any confirmed food allergies  
Yes ☐ 
No ☐ 
(i.e., confirmed by skin-prick testing or blood tests)? 
 
If Yes, what are they?  
 
 
 
 
3. 
Does eating certain foods seem to make your EoD symptoms worse?  
Yes ☐ 
No ☐ 
 
If Yes, what are the 3 specific foods/types of foods that make the effects worse? 
Food or Type of Food 
Effect 
 
 
 
 
 
 
4. 
Do you avoid eating any specific foods or types of foods due to your 
Yes ☐ 
No ☐ 
EoD symptoms?  
 
If Yes, which foods are always avoided?  
 
 
 
 
5. 
Do you avoid? (tick all that are appropriate) 
 
☐ Milk 
☐ Egg 
☐ Wheat  
☐ Soy  
 
What are the main foods that YOU DO eat? 
 
If a full diet is eaten do not list all types of foods, just write “All foods.” 
 
 
 
6. 
Do you avoid eating at certain times of the day to avoid symptoms of EoD? 
Yes ☐ 
No ☐ 
 
If Yes, please describe:  
 
 
 
 
v. 14Mar2020 
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19.4 
Appendix 4: Common Terminology Criteria for Adverse Events (version 5.0)  
The CTCAE (version 5) for download can be found at:  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_ 
Quick_Reference_5x7.pdf 
Example of Grading for Infusion-Related Reactions 
Adverse Event 
General Disorders and Administration Site Conditions 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Infusion-related 
reaction 
Mild transient 
reaction; infusion 
interruption not 
indicated; 
intervention not 
indicated 
Therapy or infusion 
interruption indicated 
but responds promptly to 
symptomatic treatment 
(e.g., antihistamines, 
NSAIDS, narcotics, IV 
fluids); prophylactic 
medications indicated 
for ≤24 hours 
Prolonged (e.g., not 
rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion); recurrence 
of symptoms following 
initial improvement; 
hospitalization indicated 
for clinical sequelae 
Life-threatening 
consequences; 
urgent intervention 
indicated 
Death 
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances. 
Example of Grading for Laboratory Abnormalities 
Adverse Event 
Grade 
1 
2 
3 
4 
5 
Growth hormone 
abnormal 
Asymptomatic; 
clinical or diagnostic 
observations only; 
intervention not 
indicated  
Symptomatic; 
medical intervention 
indicated; limiting 
instrumental ADL 
– 
– 
– 
Definition: A finding based on laboratory test results that indicate abnormal levels of growth hormone in biological specimen. 
Haptoglobin decreased 
<LLN  
– 
– 
– 
– 
Definition: A finding based on laboratory test results that indicate a decrease in levels of haptoglobin in a blood specimen. 
Hemoglobin increased 
Increase in >0–2 g/dL Increase in >2–4 g/dL Increase in >4 
g/dL  
- 
- 
Definition: A finding based on laboratory test results that indicate increased levels of hemoglobin above normal. 
Lipase increased 
>ULN –1.5 × ULN  
>1.5–2.0 × ULN; 
>2.0-5.0 × ULN and 
asymptomatic 
>2.0–5.0 × ULN 
with signs or 
symptoms; 
>5.0 × ULN and 
asymptomatic 
>5.0 × ULN and 
with signs or 
symptoms 
– 
Definition: A finding based on laboratory test results that indicate an increase in the level of lipase in a biological specimen. 
Lymphocyte count 
decreased 
<LLN–800/mm3; 
<LLN–0.8 × 10e9/L 
<800–500/mm3; 
<0.8–0.5 × 10e9/L 
<500–200/mm3; 
<0.5–0.2 × 
10e9/L 
<200/mm3; 
<0.2 × 10e9/L 
– 
Definition: A finding based on laboratory test results that indicate a decrease in number of lymphocytes in a blood specimen. 
Lymphocyte count 
increased 
– 
>4000/mm3–
20,000/mm3 
>20,000/mm3 
– 
– 
Definition: A finding based on laboratory test results that indicate an abnormal increase in the number of lymphocytes in the 
blood, effusions or bone marrow.  


 
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19.5 
Appendix 5: EGD and Colonoscopy Histology  
Details for collecting, labeling, and shipping specimens will be provided separately in the 
Histology Manual. 
Staining: The performance of the evaluations listed below will require the following stains for 
each biopsy set: 
• 
Esophagus: 
1) H&E; 2) tryptase; 3) trichrome 
 
For patients with a history of EoE and/or with a score of ≥3 on the 
dysphagia question during screening, esophageal biopsies will also be 
collected at screening and postdose. 
• 
Stomach:  
1) H&E; 2) tryptase 
• 
Duodenum: 
1) H&E; 2) tryptase 
• 
Colon:  
1) H&E; 2) tryptase 
Biopsies will be obtained from the following: 
• 
Esophagus (if patient has a history of concomitant EoE, if esophagus looks suspicious for 
EoE, or if patient is symptomatic on screening dysphagia question, quantified by a score of 
>3 on the dysphagia question on at least 1 day during screening). 
− A set of 2 fragments from the distal esophagus 
− A set of 2 fragments from the mid-proximal esophagus 
− Up to 2 extra specimens may be collected if there are any additional areas of interest. 
 
A count of ≥15 eosinophils/hpf in at least 1 esophageal site will be considered diagnostic of 
EoE for the purposes of the study.  
• 
Stomach  
− 4 specimens from separate areas of the gastric antrum (2–5 cm proximal to the pylorus) 
− 4 specimens from separate areas of the gastric corpus (2 from the proximal lesser 
curvature and 2 from the greater curvature) 
− Up to 2 extra specimens may be collected if there are any additional areas of interest. 
− 1 fragment will be collected for exploratory analysis (shipped to Allakos directly). 


 
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19.5 
Appendix 5: EGD and Colonoscopy Histology cont. 
• 
Duodenum 
− 4 fragments of duodenal mucosa from the second and third part of the duodenum 
− Up to 2 extra specimens may be collected if there are any additional areas of interest. 
− 1 fragment will be collected for exploratory analysis (shipped to Allakos directly). 
• 
Colon 
− At least 2 fragments (preferably 3 fragments) each from terminal ileum; ascending, 
transverse, descending, and sigmoid colon; and rectum 
− Up to 2 extra specimens may be collected if there are any additional areas of interest. 
− 1 fragment each will be collected from terminal ileum; ascending, transverse, 
descending, and sigmoid colon; and rectum for exploratory analysis (shipped to Allakos 
directly). 
The following will be reported for esophageal biopsies: 
• 
Maximum number of eosinophils/hpf  
• 
Maximum number of tryptase-positive mast cells/hpf 
The following histopathologic parameters will be graded from 0 (absent) to 3 (marked or severe): 
• 
Eosinophilic microabscesses  
• 
Eosinophilic degranulation 
• 
Basal zone hyperplasia  
• 
Spongiosis 
• 
Subepithelial tissue present (Y/N) 
• 
Lamina propria fibrosis: (grade only if subepithelial tissue is present)  
The following will be reported for gastric biopsies:  
• 
A highly sensitive monoclonal immunohistochemical stain will be used. The following 
histopathologic parameters will be graded using the Updated Sydney System from 
0 (absent) to 3 (marked or severe):  
− Active inflammation 
− Chronic inflammation 


 
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19.5 
Appendix 5: EGD and Colonoscopy Histology cont. 
− Intestinal metaplasia 
− Atrophy 
− Reactive gastropathy 
• 
Eosinophil and mast cell counts will be reported as: 
− Maximum number of eosinophils/hpf in at least 5 hpf on each biopsy fragment 
− Maximum number of tryptase-positive mast cells/hpf in at least 5 hpf on each biopsy 
fragment 
The following will be reported for duodenal biopsies: 
• 
Eosinophil and mast cell counts will be reported as: 
− Maximum number of eosinophils/hpf in at least 3 hpf on each biopsy fragment 
− Maximum number of tryptase-positive mast cells/hpf in at least 3 hpf on each biopsy 
fragment 
• 
Duodenal intraepithelial lymphocytosis (with counts per 100 enterocytes when 
count is >20) 
• 
Villous architecture  
The following will be reported for ileal and colonic biopsies: 
• 
Eosinophil and mast cell counts will be reported as: 
− Maximum number of eosinophils/hpf in at least 5 hpf on each biopsy fragment 
− Maximum number of tryptase-positive mast cells/hpf in at least 5 hpf on each biopsy 
fragment 
• 
In addition, the ileal and colonic biopsies will be evaluated for chronic or active 
inflammation, lymphocytic colitis, collagenous colitis, or evidence of inflammatory bowel 
disease. The presence of any of these abnormalities will be reported by the central reader 
and evaluated against eligibility criteria by the Investigator and Allakos Medical Monitor. 
Any stored tissue from biopsies of the esophagus, stomach, duodenum, or ileum may be used for 
exploratory analysis.  


 
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19.6 
Appendix 6: Sampson’s Criteria of Anaphylaxis  
ANAPHYLAXIS: Sampson’s definition of anaphylaxis (clinical definition) is the acute onset of 
illness (minutes to several hours) which involves SKIN, MUCOSAL TISSUE, or BOTH (e.g., 
generalized hives, pruritus or flushing, swollen lips-tongue uvula) with 1 OR more of the 
following (Sampson, 2006): 
• 
RESPIRATORY: Airway compromise (e.g., dyspnea, wheeze, or bronchospasm, stridor, 
reduced PEF, hypoxemia) 
• 
CIRCULATORY: Reduced blood pressure or associated symptoms of end-organ 
dysfunction (e.g., hypotonia, syncope) 
 
OR 
2 or MORE of the following that occur rapidly after exposure: 
• 
SKIN, MUCOSAL TISSUE: e.g., generalized hives, itch-flush, swollen lips-tongue-uvula 
• 
RESPIRATORY: Airway compromise (e.g., dyspnea, wheeze, or bronchospasm, stridor 
and reduced PEF) 
• 
CIRCULATORY: Reduced blood pressure or associated symptoms of end-organ 
dysfunction (e.g., hypotonia, syncope) 
• 
GASTROINTESTINAL: Persistent gastrointestinal symptoms (e.g., crampy abdominal 
pain, vomiting, nausea, diarrhea) 
 


 
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19.7 
Appendix 7: ePRO Teaching Tool for Study AK002-021  
 


 
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Appendix 7: ePRO Teaching Tool cont. 
 


 
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Appendix 7: ePRO Teaching Tool cont. 
 


 
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Appendix 7: ePRO Teaching Tool cont.  
 
 


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 3 0 of 1 4 0 
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 3 1 of 1 4 0 
C o nfi de nti al  
 
C CI


 
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19.10 Appendix 10: Additional Questions for Dysphagia and Constipation  
 
 
PID: _______________________ 
 
Date: ______________________ 
ADDITIONAL QUESTION(S) 
Instructions: This questionnaire asks about symptoms that people with your condition may have. Think of the 
last 24 hours and choose the number that best describes the intensity of your symptoms during that time. 
Please complete these every day, at approximately the same time.  
Please choose an answer by selecting only one box for each question below, as appropriate.  
Answer this question unless instructed to stop. 
Question # 1: 
Over the past 24 hours, please rate the Intensity of your difficulty swallowing (dysphagia) at 
its worst. 
 
☐ 0 – No swallowing difficulty  
 
☐ 1 
 
☐ 2 
 
☐ 3 
 
☐ 4 
 
☐ 5 
 
☐ 6 
 
☐ 7 
 
☐ 8 
 
☐ 9 
 
☐ 10 – Worst possible swallowing difficulty 
Answer this question unless instructed to stop. 
Question # 2: 
Over the past 24 hours, please rate the intensity of your constipation (difficulty passing stool) 
at its worst. 
 
☐ 0 – No constipation  
 
☐ 1 
 
☐ 2 
 
☐ 3 
 
☐ 4 
 
☐ 5 
 
☐ 6 
 
☐ 7 
 
☐ 8 
 
☐ 9 
 
☐ 10 – Worst possible constipation 
Version 06-JAN-2021 
Page 1 of 1 


 
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19.11 Appendix 11: Previous Treatments and Procedure Review 
Instructions: To be completed by Study Personnel through direct interview with Study Participant. Please ask 
questions to Study Participants, much as they appear below. This review should be conducted anytime during the 
screening period. 
1. 
Were you clinically diagnosed with EoD (sometimes called EGE) before participating in this study? 
 
Yes 
 
No 
 
2. 
Have you previously taken prescription medications specifically for the diagnosis of EoD? 
N/A, not previously diagnosed with EoD 
 
Yes* 
 No 
 
 
If yes* please list:  
 
 
All medications taken for EoD or EoD symptoms at any time should be listed on the ConMed Log. 
3. 
Have you previously taken over-the-counter (OTC) medications for symptoms of EoD  
(i.e., Zantac®, Tylenol®, Tums®)? 
Yes* 
 No 
 
 
If yes* please list:  
 
 
All medications taken for EoD symptoms at any time should be listed on the Con-Med Log. 
4. 
Have you previously tried changing your diet to help improve the symptoms of EoD? Yes* 
 No 
 
 
If yes* please describe:  
 
5. 
Have you previously tried changing your eating habits to help improve the symptoms of EoD? 
 
Yes* 
 No 
 
 
If yes*please describe:  
 
6. 
Have you previously tried other methods to help improve the symptoms of EoD 
(i.e., acupuncture, pressure point therapy)?  
Yes* 
 No 
 
 
If yes* please describe:  
 
7. 
How many EGD and/or colonoscopies have you had in the last 5 years? 
EGD:  
 
Colonoscopy:  
 
8. 
What was the date of the last EGD/colonoscopy prior to screening for this study? 
EGD:               /              /               
Colonoscopy:              /             /              
 
 DD   /    MM   /  Year 
DD  /   MM   /  Year 
Additional Comments  
 
 
 
 
 
 
 
 
 
Name of Person completing Previous Treatments and Procedure Review 
Date 


 
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19.12 Appendix 12: Hepatitis B and Hepatitis C Serologic Testing Details 
19.12.1 Hepatitis B Testing Details 
HBsAg positive patients are excluded. However, in case of past infections/vaccinations in order 
to qualify, the patient’s testing status needs to align with the information in Table 6. 
Table 6 
Hepatitis B Testing 
Past Infection (Resolved) 
Or 
Vaccinated 
HBsAg 
Negative 
HBsAg 
Negative 
Anti-HBc 
Positive 
Anti-HBc 
Negative 
Anti-HBs 
Positive 
Anti-HBs 
Positive 
 
19.12.2 Hepatitis C Testing Details 
Anti-HCV positive and HCV-RNA positive are excluded. In order to qualify for enrollment, the 
patient’s testing status needs to align with the information in Table 7. 
Table 7 
Hepatitis C Testing 
Non-Reactive 
Or 
Past Infection (Resolved) 
Anti- HCV 
Negative 
Anti- HCV 
Positive 
HCV RNA 
Negative 
 


 
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19.13 Appendix 13: Open-Label Extension Period – Optional  
19.13.1 Summary of the Open-Label Extended Dosing Period 
Patients who receive all 6 infusions of study drug (AK002 or placebo), complete study visits 
through Day 176 (±3) of the double-blind treatment period and meet extended dosing eligibility 
criteria will be given the option to receive 6 doses of AK002 through the Open-Label Extended 
Dosing (OLE) period.  
Patients will follow the visits and procedures of the double-blind period of the study until 
starting the OLE period of the study. At least 1 day after Day 176 (±3), eligible patients 
participating in the OLE period will begin following the OLE Schedule of Assessments (Table 8) 
and will no longer follow the double-blind period of the study Schedule of Assessments 
(Table 2). It is important that the first dose of the OLE period is started after Day 176 to allow 
the patient to receive prednisone premedication 12–24 hours prior to the first dose of AK002 in 
the OLE period. The extended dosing period is summarized as follows:  
• 
The Investigator will evaluate whether the patient is eligible for OLE. If eligible, the patient 
will be given the option to participate in the OLE period and receive 6 doses of open-label 
AK002. 
• 
On OLE Dose 1, eligible patients who completed all double-blind Day 176 required 
procedures will be instructed to begin following the OLE Schedule of Assessments 
(Table 8). 
• 
All patients will receive 80 mg oral prednisone 12–24 hours prior to the first infusion in the 
OLE period. An approved alternative(s) may be used with the approval of the Medical 
Monitor. Premedication may be administered prior to subsequent infusions at the 
Investigator’s discretion, but only with written approval from the Medical Monitor.  
• 
OLE patients will receive 6 doses of open-label AK002 (OLE Days 1, 29, 57, 85, 113, and 
141). All open-label AK002 infusions will be given at a dose of 3 mg/kg. 
• 
Patients will remain at the site for at least 1 hour of observation after each dose. In the event 
of an IRR, the patient may require prolonged observation (>1 hour or until the symptoms 
resolve) as per the Investigator’s discretion.  
• 
Patients will be followed for approximately 8 weeks after last dose. Follow-up visits will 
occur on Day 344 (±7) and Day 372 (±7) (OLE Day 169 and OLE Day 197, respectively).  
• 
If absolute lymphocyte and/or eosinophil counts have not recovered by the OLE Day 197 
visit, patients will return approximately every 28 days for extended follow-up until counts 
have recovered. 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 136 of 140 
Confidential 
19.13.2 OLE Objective 
The objective of the OLE period is to evaluate long-term safety and tolerability of up to 6 doses 
of open-label AK002. The Medical Monitor will review OLE period data relating to safety and 
tolerability throughout the course of OLE dosing. 
19.13.3 OLE Eligibility Criteria 
Following completion of the randomized, double-blind, placebo-controlled treatment (all 
6 doses) and the Day 176 visit, eligible patients will have the option to receive 6 doses of 
open-label AK002 through participation in the OLE period.  
Patients who are not eligible for OLE or who choose not to participate in the OLE period will 
continue to follow the study Schedule of Assessments for the double-blind period of the study 
(Table 2). 
19.13.3.1 OLE Inclusion Criteria 
Patients are eligible to participate in the OLE period if all of the following criteria are met: 
1) 
Patient completed the randomized, double-blind, placebo-controlled treatment period, 
defined as having received all 6 infusions of study drug (AK002 or placebo) and completed 
the Day 176 visit.  
2) 
Patient is willing and able to comply with the OLE period Schedule of Assessments 
(Table 8), including receiving the first open-label AK002 infusion at least 1 day after the 
Day 176 (±3) visit. 
19.13.3.2 OLE Exclusion Criteria 
Patients are not permitted to participate in the OLE period if any of the following criteria are 
met: 
1) 
Previous administration of the study drug (AK002 or placebo) was poorly tolerated by the 
patient, in the opinion of the Investigator. 
2) 
Any other reason that in the opinion of the Investigator or Medical Monitor makes the 
patient unsuitable for participation in the OLE period. 
19.13.4 OLE Treatment 
Formulation, storage, preparation, and administration of the open-label AK002 drug product for 
OLE will be consistent with Section 9. Study Treatment of this protocol and the AK002-021 
Pharmacy Manual. 


 
Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 137 of 140 
Confidential 
Twelve to 24 hours prior to the first open-label AK002 infusion only, all patients will receive 
80 mg oral prednisone. An approved alternative(s) may be used with the approval of the Medical 
Monitor. This dose of prednisone premedication should be recorded in the Concomitant 
Medications CRF of both the AK002-021 double-blind treatment period database and the 
AK002-021 OLE period database. Premedication may be administered prior to subsequent 
infusions at the Investigator’s discretion, but only with written approval from the Medical 
Monitor.  
The first OLE infusion of AK002 will be administered at a dose of 3 mg/kg over at least 4 hours 
after Day 176 (±3). The subsequent infusions on OLE Days 29, 57, 85, 113, and 141 (±3), 
depending on the patient’s tolerance per the Infusion Rate Schedules in the AK002-021 
Pharmacy Manual can be given over ≥1 hour. Any reduction in infusion rate due to tolerability 
will not be considered a deviation from the protocol. If the infusion is slowed or interrupted, the 
infusion must be completed within 8 hours of preparation (prior to expiry).  
The patient will be observed for at least 1 hour (or more as per the Investigator’s discretion) after 
the end of all infusions. In the event of an IRR, the patient may require prolonged observation 
(>1 hour or until the symptoms resolve), as per the Investigator’s discretion. Patients will also be 
instructed to immediately contact the study doctor if any reactions occur after discharge. 
19.13.5 OLE Procedures and Guidelines 
Apart from differences in the Schedule of Assessments beginning after double-blind Day 176 
(±3), the OLE period of the study will be conducted in accordance with the protocol. This 
includes prohibited medications, dietary and lifestyle restrictions, AK002 preparation and 
administration, study assessment and procedure guidelines including the EGD and colonoscopy 
with biopsy, AE reporting, withdrawal criteria and stopping rules, data collection and 
management, and ethical and regulatory requirements. 
The Investigator will evaluate whether the patient is eligible for the OLE period. After 
completion of procedures on Day 176 (±3), eligible patients that choose to participate in the OLE 
period will begin following the OLE Schedule of Assessments (Table 8) and will receive the first 
open-label AK002 infusion.  
 
 


Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 3 8 of 1 4 0 
C o nfi de nti al  
T a ble  8 
St u d y A K 0 0 2 - 0 2 1 Sc he d ule of Assess me nts : O pe n -L a bel E xte n si o n P eri o d  
Ass ess me nt Descri pti o n  
Scree ni n g  
O pe n -L a bel E xte n de d D osi n g ( 2 0 wee ks)  
O L E F oll o w -U p ( ≥8 wee ks) 2 2 
N o Visit 2 
O L E D os e 1  
D a y 1 7 6  
[ O L E D a y 1] 
( ± 3 d a ys) 
O L E D os e 2  
D a y 2 0 4  
[ O L E D a y 2 9] 
( ± 3 d a ys) 
O L E D os e 3  
D a y 2 3 2  
[ O L E D a y 5 7] 
( ± 3 d a ys) 
O L E D os e 4  
D a y 2 6 0  
[ O L E D a y 8 5] 
( ± 3 d a ys) 
O L E D os e 5  
D a y 2 8 8  
[ O L E D a y 1 1 3] 
( ± 3 d a ys) 
O L E D os e 6  
D a y 3 1 6  
[ O L E D a y 1 4 1] 
( ± 3 d a ys) 
D a y 3 4 4  
[ O L E D a y 1 6 9] 
( ± 3 d a ys) 
D a y 3 7 2  
[ O L E D a y 1 9 7] 
( ± 7 d a ys) o r E T 2 1 
E val uate Eli gi bilit y f or O L E Peri o d 2 
X 2 
X 2 
 
 
 
 
 
 
 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
B as eli ne Diet C o m plia nce 4 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
Wei g ht a n d Vital Si g ns
5, 6 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
T otal Ser u m I g E 7, 8 
 
 
 
 
 
 
X 1 
 
X  
C o m plete Bl o o d C o u nt wit h Differe ntial 7, 9 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
C he mistr y 7, 1 0 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X  
X  
P har mac o ki netics 7, 1 1 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
A nti - dr u g A nti b o dies7, 1 2 
 
X 1 
X 1 2 
X 1 2 
X 1 2 
X 1 2 
X 1 2 
X 1 2 
X 
Uri nal ysis 7, 1 3 
 
X 1 
X 1 
 
 
 
 
 
X  
Uri ne Pre g na nc y T est 7,1 4 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
 
 
Pre me dicati o n: Pre d nis o ne 1 5 
X  
 
 
 
 
 
 
 
 
Access I R T: I P Kit Assi g n me nt  
 
X 
X 
X  
X 
X 
X 
 
 
A K 0 0 2 A d mi nistrati o n 1 6 
 
X 
X 
X  
X 
X 
X 
 
 
P ost -D os e O bs er vati o n Peri o d 1 7 
 
X 
X 
X  
X 
X 
X 
 
 
e P R O Q uesti o n naire ( will i ncl u de 
A d diti o nal  Q uesti o ns) 2 3 
< ----------------------------------------------------------C o m plete electr o nicall y o ne ti me dail y ----------------------------------------------------------> 
S y m pt o m- Directe d P h ysical E xa m 1 8 
 
X 
X 
X  
X 
X 
X 
X 
X 
E G D a n d C ol o n os c o p y wit h Bi o ps y 
C ollecti o n 1 9 
 
 
 
 
 
 
 
X 
 
C o nc o mita nt Me dicati o ns  
 
X  
X  
X  
X  
X  
X  
X  
X  
A d vers e E ve nts 2 0 
 
X 
X 
X  
X 
X 
X 
X 
X 
C CI


Pr ot oc ol A K 0 0 2 - 0 2 1 
A m e n d m e nt 2 
Dat e: 1 6 J u ne 2 0 2 2 
All a k os I nc.  
Pa ge 1 3 9 of 1 4 0 
C o nfi de nti al  
A D A:  
A nti -A K 0 0 2 a nti b o d y  
E T:  
E arl y T er mi nati o n  
I R T: 
I nt era cti ve Res p o nse T ec h n ol o g y 
C B C: 
C o m pl et e bl o o d c o u nt  
F S H:  
F ollicle -sti m ul ati n g h or m o ne 
 
  
E C G:   
El ectr ocar di o gra m 
h C G: 
H u m a n C h ori o ni c G o na d otr o pi n  
 
 
e P R O: el ectr o nic Pati e nt Re p ort e d O ut c o m e  
I P: 
I n vesti gati o nal Pr o d uct 
P K:  
P har ma c o ki neti cs  
T a bl e 8  N otes 
1) 
Refer t o assess me nt ta ble n ote  n u m ber  f or s pe cific ti mi n g (e. g., pre d ose, d uri n g i nf usi o n, p ost d ose). 
2) 
T he I n vesti gat or will e val uat e w het her t he pati e nt is eli gi bl e f or t he O L E peri o d per Secti o n 1 9. 1 3. 3 . I m m e diatel y aft er t he d o u ble- bli n d Da y 1 7 6 ( ± 3)  assess m e nts, eli gi bl e 
pati e nts t hat c h o ose t o parti ci pat e 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 ul e of Assess m e nts  a n d will rec ei ve t he first o pe n -la bel A K 0 0 2 i nf usi o n. Pre d nis o ne 
pre me di cati o n will  be a d mi nist ere d aft er t he d o u bl e- bli n d Da y 1 7 6 assess m e nts are c o m pl et e d.  
3) 
 s h o ul d be t he first assess m e nt c o m pl et e d b y t he patie nt at t he be gi n ni n g of t he st u d y visit pri or t o ot her assess m e nts.  
4)  P atie nts s h o ul d m ai ntai n t he baseli ne diet c o nsiste ntl y t hr o u g h o ut t he st u d y. Diet c o m plia nce will be disc usse d d uri n g st u d y visits a n d a n y vari a nc e will be d oc u m e nt e d.  
5) 
W ei g ht will be m eas ure d pre d ose o n  all O L E d osi n g da ys , Da y 3 4 4 , a n d Da y 3 7 2 or E T.  
6) 
O n all O L E d osi n g da ys, v it al si g ns will be m eas ure d wit hi n 3 0 mi n ut es  pre d ose, 1 5 ( ± 5) mi n u tes after i nf usi o n start, wit hi n 1 5 mi n ut es  f oll o wi n g t he e n d of i nf usi o n a n d j ust 
pri or t o disc har ge . Pati e nt s h o ul d be at rest f or ≥5 mi n ut es bef ore vit al si g ns (s yst olic a n d diast olic bl o o d press ure, p ulse, b o d y t e m perat ure, a n d res p irat or y rate) are m eas ure d. 
7) 
Refer t o  t he La b orat or y Ma n ual f or c olle cti o n, pr oc essi n g, a n d s hi p m e nt i nstr ucti o ns. Sa m pl es s h o ul d be s hi p pe d o n t he sa m e da y as c oll ecti o n. 
8) 
Bl o o d f or t ot al ser u m I g E will be o btai ne d pre d ose o n O L E D ose 6  ( Da y 3 1 6) a n d a gai n o n Da y 3 7 2 or E T.  
9) 
Bl o o d f or C B C wit h differe nti al will be o bt ai ne d at all O L E peri o d st u d y visits. O n O L E d osi n g da ys  t he bl o o d sa m ple will be dra w n  j ust pri or t o e ac h i nf usi o n a n d 1 h o ur 
( ± 1 5 mi n ut es) after t he e n d of e ac h i nf usi o n. 
1 0) Bl o o d f or c he mistr y will be o bt ai ne d at all O L E peri o d st u d y visits. O n O L E d osi n g da ys  bl o o d f or c he mistr y will be dra w n pre d ose.  
1 1) Bl o o d f or P K will be o bt ai ne d at all O L E peri o d st u d y visits. O n O L E d osi n g da ys  bl o o d f or P K will be dra w n pre d ose.  
1 2) Bl o o d f or A D A will be o bt ai ne d pre d ose o n O L E D ose 1  a n d o n Da y 3 7 2 or E T. F or O L E D ose s 2,  3, 4, 5 a n d 6 , bl o o d f or A D A will be o bt ai ne d o nl y if a s us pecte d 
i m m u n o ge nicit y-relate d A E occ urs. 
1 3) Uri ne f or uri nal ysis will be o btai ne d pre d ose o n O L E D ose 1 , O L E D ose 2, a n d Da y 3 7 2. 
1 4) F or fe m al es of c hil d beari n g p ot e ntial, uri ne will be c oll ecte d, test e d, a n d pre g na nc y res ult c o nfir me d pre d ose o n all d osi n g da ys. 
1 5) All pati e nts will self-a d mi nist er 8 0 m g oral pre d nis o ne 1 2 – 2 4 h o urs pri or t o t he first i nf usi o n. A n a p pr o ve d alt er nati ve(s) m a y be use d wit h t he a p pr o val of t he Me dic al 
M o nit or. Pre m e di cati o n ma y be a d mi nistere d pri or t o s u bse q ue nt i nf usi o ns at t he I n vesti gat or’s discreti o n, b ut o nl y wit h writte n a p pr o val  fr o m t he Me di cal M o nit or. T his d ose 
of pre d nis o ne pre me dic ati o n pri or t o t he first i nf usi o n m ust be a d mi nist ere d after  all d o u ble- bli n d Da y 1 7 6 assess m e nts are perf or m e d a n d s h o ul d be rec or de d i n t he 
C o nc o mit a nt Me dic ati o ns C R F of b ot h t he A K 0 0 2 -0 2 1 d o u bl e-bli n d treat m e nt peri o d dat a base a n d t he A K 0 0 2 -0 2 1 O L E peri o d data base.  
C CI
C CI
C CI


Protocol AK002-021 
Amendment 2 
Date: 16 June 2022 
Allakos Inc. 
Page 140 of 140 
Confidential 
Table 8 Notes cont. 
16) Open-label AK002 will be administered as a single peripheral intravenous infusion over at least 4 hours on OLE Dose 1 and over at least 1 hour on subsequent dosing days. 
Refer to the AK002-021 Pharmacy Manual for detailed administration and infusion rate schedule instructions. 
17) Patients will remain under observation at the site for at least 1 hour after the end of each infusion. In the event of an IRR, the patient may require prolonged observation 
(>1 hour or until the symptoms resolve), as per the Investigator’s discretion. Patients will also be instructed to immediately contact the study doctor if any reactions occur after 
discharge. 
18) If a new or worsening symptom (or clinically significant finding) is observed or reported, the Investigator or designee will determine whether a symptom-directed physical 
examination is warranted and should perform it at any time or multiple times during a visit (predose, during infusion, and/or postdose).  
19) An EGD and colonoscopy with biopsy collection will be performed on Day 344 (±3) or 28 (±3) days after last dose of study drug if ET. The EGD and colonoscopy should 
take place on the same day. EGD and colonoscopy biopsies will be collected, processed, and shipped in accordance with Section 11.2.4, Appendix 5, and the Histology 
Manual. The patient should arrive fasting for the EGD and colonoscopy procedures, as specified by instructions form the EGD provider, and all concomitant medications 
provided to the patient prior to or during EGD and colonoscopy procedures should be captured in the source data and electronic CRF. 
20) All AE, including AESI and SAE, will be captured throughout the entire OLE period until Day 372 or ET. Adverse events will be assessed and recorded in the CRF of the 
AK002-021 OLE period database beginning from the start of the first open-label infusion during the OLE Dose 1 visit. 
21) ET visits should be conducted 28 (±3) days after last dose of open-label AK002 or prior to this, if necessary, to ensure compliance with the visit. If a patient discontinues the 
study >28 days after last dose of study drug, the ET visit should be conducted as soon as possible. 
22) If absolute lymphocyte and/or eosinophil counts do not recover (to normal range or baseline levels) by Day 372 or ET, extended follow-up visits are required every 
28 (±3) days thereafter to monitor blood counts until they recover. Extended follow-up visits consist of blood collection for CBC with differential and collection of AESI and 
SAE. 
23) Patients entering into the OLE period of the study should continue completing the PRO daily. The PRO should be completed around the same time each day. Patients should 
continue completing the additional questions that they were completing during the double-blind period of the study. 
 

SAP_001.pdf: 
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study 
to Evaluate the Efficacy and Safety of AK002 in Patients with Moderately to 
Severely Active Eosinophilic Duodenitis Who Have an Inadequate Response 
with, Lost Response to, or Were Intolerant to Standard Therapies 
NCT Number: NCT04856891 
Document Date: 29 Jun 2022 


 
 
Statistical Analysis Plan for Protocol AK002-021 
 
Protocol Title 
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of AK002 in Patients with 
Moderately to Severely Active Eosinophilic Duodenitis Who Have an 
Inadequate Response with, Lost Response to, or Were Intolerant to 
Standard Therapies 
Protocol Number 
AK002-021 
Protocol Version 
Amendment 2 
Protocol Dates 
Amendment 2 
16 June 2022 
Amendment 1 
07 July 2021 
Original 
06 January 2021 
Study Drug 
AK002 (lirentelimab) 
Study Phase 
3 
IND Number 
135158 
Sponsor 
Allakos Inc., 825 Industrial Road, Suite 500, San Carlos, CA 94070 USA 
SAP Version 
1 
SAP Date 
29 June 2022 
 
 
 
 
 
 
 
 
 
Page 1 of 63 


Protocol AK002-021 
Statistical Analysis Plan – Version 1 
29 June 2022 
Allakos Inc. 
Page 2 of 63 
Confidential 
 
 
 
 
Signature Page 
 
 
 
 
Prepared by: 
 
 
 
 
 
Allakos, Inc. 
 
PhD 
Biometrics 
30-Jun-2022 | 08:47 PDT 
Date 
 
 
 
Reviewed and 
Approved by: 
 
 
MD, MBA 
Date 
 
Allakos, Inc. 
30-Jun-2022 | 08:53 PDT 


Protocol AK002-021 
Statistical Analysis Plan – Version 1 
29 June 2022 
Allakos Inc. 
Page 3 of 63 
Confidential 
 
 
 
Table of Contents 
Statistical Analysis Plan for Protocol AK002-021 .......................................................................1 
Signature Page ................................................................................................................................2 
Table of Contents ...........................................................................................................................3 
List of In-Text Tables ..............................................................................................................7 
List of Abbreviations ...............................................................................................................8 
Revision History ...........................................................................................................................11 
1. 
Introduction .........................................................................................................................12 
2. 
Study Objectives ..................................................................................................................12 
2.1 
Primary Objective – Primary Endpoints ....................................................................12 
2.2 
Secondary Objectives – Secondary Endpoints ..........................................................13 
2.3 
Exploratory Objectives – Exploratory Endpoints ......................................................13 
2.4 
Safety Objectives – Safety Endpoints .......................................................................13 
3. 
Study Design.........................................................................................................................14 
3.1 
General Description ...................................................................................................14 
3.2 
Study Treatment ........................................................................................................21 
3.2.1 Treatment, Dose, and Mode of Administration .............................................21 
3.2.2 Duration of Study ..........................................................................................21 
3.2.3 Methods of Assigning Subjects to Treatment Group ....................................21 
3.3 
Blinding .....................................................................................................................21 
3.4 
Hypotheses ................................................................................................................21 
3.5 
Determination of Sample Size ...................................................................................22 
4. 
Definitions ............................................................................................................................22 
4.1 
Terminology and Definitions ....................................................................................22 
4.2 
Target of Estimation ..................................................................................................23 


Protocol AK002-021 
Statistical Analysis Plan – Version 1 
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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 .......................................................................................................25 
4.2.4 Intercurrent Events ........................................................................................25 
4.2.5 Strategy for Handling Intercurrent Events ....................................................25 
4.2.6 Summary Measure of the Estimand ..............................................................25 
5. 
Statistical Methods ..............................................................................................................25 
5.1 
General Methodology ................................................................................................25 
5.2 
Visit Window and Unscheduled Assessments ..........................................................27 
5.3 
Adjustment for Covariates .........................................................................................29 
5.4 
Handling of Dropouts, Missing Data, and Data Discrepancies .................................29 
5.4.1 Missing Duodenal Tissue Eosinophil Count at Week 24 ..............................29 
5.4.2 Missing Daily PRO Scores at Weeks 23–24 .................................................29 
5.4.3 Missing or Partial Dates of Adverse Events or Concomitant Medications ...30 
5.5 
Interim Analysis ........................................................................................................31 
5.6 
Timing of Data Analyses ...........................................................................................31 
5.7 
Multicenter Study ......................................................................................................31 
5.8 
Multiple Comparisons/Multiplicity Adjustment .......................................................32 
5.9 
Examination of Subgroups ........................................................................................32 
6. 
Statistical Analysis ...............................................................................................................33 
6.1 
Analysis Populations .................................................................................................33 
6.1.1 Safety Population ...........................................................................................33 
6.1.2 Intent-to-Treat Population .............................................................................33 
6.1.3 Modified Intent-to-Treat Population .............................................................33 
6.1.4 Per Protocol Analysis Population ..................................................................33 


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Statistical Analysis Plan – Version 1 
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Allakos Inc. 
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6.1.5 Primary Analysis Population .........................................................................33 
6.2 
Disposition of Subjects ..............................................................................................34 
6.3 
Protocol Deviations ...................................................................................................35 
6.4 
Demographics and Baseline Subject Characteristics ................................................35 
6.5 
Baseline Disease Characteristics ...............................................................................35 
6.6 
Medical History .........................................................................................................35 
6.7 
Electrocardiogram .....................................................................................................35 
6.8 
Pregnancy Test ..........................................................................................................36 
6.9 
Baseline Diet .............................................................................................................36 
6.10 
Treatments .................................................................................................................36 
6.10.1 Treatment Compliance and Extent of Exposure ............................................36 
6.10.2 Prior, Concomitant, and Newly Initiated Medications ..................................36 
6.11 
Analysis of Primary Efficacy Endpoints ...................................................................37 
6.11.1 Analysis of the First Co-Primary Endpoint ...................................................37 
6.11.2 Sensitivity Analysis of the First Co-Primary Endpoint .................................38 
6.11.3 Subgroup Analysis of the First Co-primary Endpoint ...................................38 
6.11.4 Analysis of the Second Co-Primary Endpoint...............................................38 
6.11.5 Sensitivity Analyses of the Second Co-Primary Endpoint ............................39 
6.11.6 Supplementary Analyses ...............................................................................41 
6.12 
Analysis of Secondary Efficacy Endpoints ...............................................................41 
6.12.1 Change in Tissue Eosinophil Count ..............................................................41 
6.12.2 Proportion of Subjects Achieving Peak Duodenal Intraepithelial Eosinophil 
Count of ≤1 Cell/hpf ......................................................................................41 
6.12.3 Proportion of Treatment Responders .............................................................42 
6.12.4 Proportion of Subjects with ≥50% Reduction and ≥70% Reduction in 
TSS from Baseline to Weeks 23–24 ..............................................................42 
6.12.5 Change in Weekly TSS Over Time ...............................................................42 


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CCI 
CCI 
6.13 
Analysis of Exploratory Endpoints ...........................................................................42 
6.13.1 Change in CCI 
  ................................................................................................ 42 
6.13.2 Change in CCI 
  ........................................................................................................................ 42 
6.13.3 Change in CCI 
  .......................................................... 42 
6.13.4 Change in .......................................................................................................43 
6.13.5 
6.13.6 
6.14 
Analysis of Pharmacokinetic Endpoint .....................................................................44 
6.15 
Safety Analyses .........................................................................................................44 
6.15.1 Adverse Events ..............................................................................................44 
6.15.2 Laboratory Test .............................................................................................45 
6.15.3 Vital Signs, Height and Weight, and Other Safety Measures .......................46 
6.15.4 Electrocardiogram .........................................................................................46 
6.15.5 Physical Examination ....................................................................................46 
6.15.6 Analysis of Anti-Drug Antibody ...................................................................46 
7. 
Validation .............................................................................................................................46 
8. 
References ............................................................................................................................47 
9. 
Appendices ...........................................................................................................................48 
9.1 
Appendix 1: Effect of Missing Data on the Weekly Mean of TSS ...........................49 
9.2 
Appendix 2: Intercurrent Events ...............................................................................51 
9.3 
Appendix 3: List of Tables, Figures, and Listings ....................................................53 
9.4 
Appendix 4: Example SAS Codes .............................................................................63 
CCI 
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Statistical Analysis Plan – Version 1 
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CCI 
 
List of In-Text Tables 
Table 1 
Schedule of Assessments .......................................................................................16 
Table 2 
Terminology and Definitions .................................................................................22 
Table 3 
Analysis Window Rules for ...................................................................................27 
Table 4 
Analysis Window Rules for Vital Sign and Laboratory Tests...............................28 
Table 5 
Analysis Window Rules for PK Concentration and ADA .....................................28 
Table 6 
Analysis Window Rules for Blood Histamine and Urinalysis...............................29 
Table 7 
Standard Errors for the Mean Weekly TSS Diaries by Number of 
Daily Diaries Missing Averaged over 500 Simulations ........................................50 


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Statistical Analysis Plan – Version 1 
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List of Abbreviations 
 
ADA 
Anti-drug antibody 
ADaM 
Analysis Data Model T 
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 
eCDF 
empirical cumulative distribution function 
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture (system) 
EG 
Eosinophilic gastritis 
EGD 
Esophago-gastro-duodenoscopy 
EGE 
Eosinophilic gastroenteritis 
EoD 
Eosinophilic duodenitis 
EoE 
Eosinophilic esophagitis 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FSH 
Follicle-Stimulating Hormone 
hpf 
High power field 
ICE 
Intercurrent events 
ICH 
International Conference on Harmonization 
ICF 
Informed Consent Form 
IRT 
Interactive Response Technology 
ITT 
Intent-to-treat (population) 


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IV 
Intravenous 
LLN 
Lower limit of normal 
LLOQ 
Lower limit of quantification 
LSM 
Least squares mean 
MAR 
Missing at random 
MCAR 
Missing completely at random 
MCMC 
Markov Chain Monte Carlo (method) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple imputation(s) 
MITT 
Modified intent-to-treat (population) 
MMRM 
Mixed Model for Repeated Measures 
MNAR 
Missing not at Random 
p-value 
Probability value 
PD 
Pharmacodynamics 
PE 
Physical examination 
CCI 
 
CCI 
PK 
Pharmacokinetic(s) 
PP 
Per protocol (population) 
PPI 
Proton pump inhibitor(s) 
PRO 
Patient-reported outcome 
PT 
Preferred term 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical analysis system 
SD 
Standard deviation 
SE 
Standard error(s) 
SDTM 
Study Data Tabulation Model 
CCI 
 
 
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 


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TSS 
Total Symptom Score 
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 
29 June 2022 
1 
Initial document 


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1. 
Introduction 
This statistical analysis plan (SAP) describes the rules and conventions to be used in the analysis 
and presentation of efficacy and safety of AK002 in subjects with moderate-to-severe 
eosinophilic duodenitis (EoD) who have an inadequate response with, lost response to, or were 
intolerant to standard therapies, as planned for the clinical protocol. 
 
The SAP describes 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 AK002-021 Amendment 2, dated 16 June 2022, and the 
associated electronic case report forms (eCRF). 
 
2. 
Study Objectives 
 
2.1 
Primary Objective – Primary Endpoints 
The primary objectives of the study are to evaluate the efficacy and safety of 6 doses of AK002 
in subjects with moderate to severe EoD when compared with placebo. 
 
Efficacy will be evaluated by 2 co-primary endpoints: 
1) 
First co-primary endpoint- Proportion of Tissue Eosinophil Responders at Week 24: 
A responder is a subject achieving a mean duodenal eosinophil count ≤15 cells/hpf in 3 
highest duodenal hpf 
2) 
Second co-primary endpoint- Change in TSS from baseline to Weeks 23–24 as measured 
by the Patient Reported Outcome (PRO) questionnaire. 
The PRO Total Symptom Score (TSS) is comprised of the following 6 symptoms: 
− Abdominal pain intensity 
− Nausea intensity 
− Fullness before finishing a meal intensity 
− Loss of appetite intensity 
− Bloating intensity 
− Abdominal cramping intensity 


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2.2 
Secondary Objectives – Secondary Endpoints 
The secondary objectives are to characterize further the efficacy of AK002 in subjects with EoD 
as measured by: 
• 
Percent change in tissue eosinophils from baseline to Week 24 
• 
Proportion of subjects achieving mean eosinophil count ≤1 cell/hpf in 3 highest duodenal 
hpf at Week 24 
• 
Proportion of treatment responders at Weeks 23- 24. Responder is defined as >30% 
improvement in TSS symptom score and mean eosinophil count ≤15 cells/hpf in 3 highest 
duodenal hpf 
• 
Proportion of subjects who achieve ≥50% reduction in TSS from baseline to Weeks 23–24 
• 
Proportion of subjects who achieve ≥70% reduction in TSS from baseline to Weeks 23–24 
• 
Percent change in weekly TSS over time 
 
2.3 
Exploratory Objectives – Exploratory Endpoints 
The exploratory objectives are to evaluate the effect of AK002 by comparing AK002 to placebo 
treatment for the following parameters: 
• 
Change from baseline in CCI 
over time 
• 
Changes in CCI 
from baseline compared to post-treatment in the 
• 
Change from baseline in CCI 
over time 
• 
Change from baseline in CCI 
over time 
 
2.4 
Safety Objectives – Safety 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, action taken, and outcome, serious adverse events (SAE) and adverse events 
(AE) leading to study drug withdrawal 
• 
Anti-drug (AK002) antibody (ADA) 
• 
Blood chemistry 
• 
Hematology 
CCI 


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• 
Urinalysis 
• 
Physical examination 
• 
Changes in vital signs 
• 
Changes in concomitant medication use due to AE 
 
3. 
Study Design 
 
3.1 
General Description 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the efficacy and safety of AK002 in subjects with moderately to severely active EoD without EG 
who have an inadequate response, lost response, or were intolerant to standard therapies. 
Subjects enrolled in the study will receive 6 infusions of placebo or AK002 administered every 4 
weeks and will be followed for 12 weeks after the last dose unless subjects elect to enter the 
optional long-term extension of the study. 
 
Subjects who have signed the informed consent form (ICF) will be screened during 21-45 days 
prior to Study Day 1. 
 
The study will be carried out as follows: 
• 
A screening period of 21–45 days with baseline evaluations for study eligibility, including 
active symptoms of disease (gathered by the patient reported outcome [PRO] questionnaire 
completed during screening) and EGD and colonoscopy (performed on the same day) with 
biopsy. 
• 
Stool antigen test for Helicobacter pylori (H. pylori) will be assessed during screening to 
confirm no active H. pylori infection exists. If H. pylori is detected in tissue biopsies by the 
central pathologist, the patient should be excluded from the trial. 
• 
If subjects meet histology and symptom eligibility criteria, they will be randomized after 
being stratified by the highest weekly TSS of disease activity recorded during the screening 
period (<28 or ≥28 strata). The interactive response technology (IRT) will randomly assign 
subjects 1:1 to receive AK002 or placebo. 
• 
Pre-study medications and dietary restrictions will remain unchanged throughout the study. 
Systemic or topical steroids above 10 mg prednisone will not be allowed except as a 
premedication prior to the first infusion only or due to unforeseen medical circumstances 
where it is deemed to be medically necessary to treat an unrelated medical condition or to 
treat an IRR that occurs during infusion. 


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CCI 
CCI 
 
• 
Eligible subjects will receive the first dose of placebo or AK002 (3 mg/kg) on Day 1 with 
premedication of 80 mg oral prednisone 12–24 hours prior to the start of the infusion. 
• 
If the study drug is well tolerated (no stopping rules being met), subjects will receive 
additional doses of placebo or AK002 (3 mg/kg) on Days 29, 57, 85, 113, and 141. With the 
exception of Day 1, steroid premedication will only be allowed with the written approval of 
the Medical Monitor. 
• 
Subjects will remain at the site for at least 1 hour of observation following the end of the 
infusion. 
• 
A repeat EGD with biopsy will be performed on Day 169 (±3) or 28 (±3) days after last 
dose of study drug if subject is terminated early (between the Day 29 visit and the Day 169 
visit). 
• 
Daily administration of the PRO questionnaire (including additional questions) throughout 
the study and the follow-up period for all patients. 
• 
Patients will rate their impression of disease severity 
and disease improvement 
at specified time points during the study. 
• 
Patients will be prompted to answer additional questions about dysphagia and constipation 
on a daily basis during screening and throughout the study. These will be completed 
following the PRO questionnaire. 
• 
Follow-up will occur for 84 (±3) days after the last dose unless subjects decide to enter the 
long-term, open-label extension (OLE) of the study. Follow-up visits for subjects opting not 
to enter the extension study will occur on Days 176 (±3), 197 (±3), and 225 (±3). 
• 
Patients who receive all 6 doses of study drug have the option to receive AK002 by entering 
into the OLE period of the study if all eligibility criteria for the OLE period are satisfied. 
Patients who enter the OLE period of the study may begin the extension dosing 1 day after 
completing the Day 176 visit of this protocol. Open-label extension patients will not 
complete the Day 197 or Day 225 procedures under the double-blind period of the study. 
• 
Eligible patients who choose to participate in the OLE period will begin following the 
OLE Schedule of Assessments (SOA) after completing the Day 176 double-blind period 
procedures and will receive the first dose of open-label AK002 approximately 1 week after 
Day 169 (on Day 177). 
• 
Total study duration is approximately 35–37 weeks. For subjects entering the OLE period 
of the study, the total study duration is approximately an additional 28–30 weeks. 
 
The overall schedule of procedures and assessments are presented in Table 1. 


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Table 1 
Schedule of Assessments 
 
 
 
 
 
 
Assessment Description 
Screening 
(21–45 days) 
Treatment Period 
(20 weeks) 
Follow-Up Period30 
(12 weeks) 
Baseline1 
Prior to 
Day 1 
Dose 1 
Day 12 
Day 8 
(±2 days) 
Day 15 
(±2 days) 
Dose 2 
Day 29 
(±3 days) 
Dose 3 
Day 57 
(±3 days) 
Dose 4 
Day 85 
(±3 days) 
Dose 5 
Day 113 
(±3 days) 
Dose 6 
Day 141 
(±3 days) 
Day 169 
(±3 days) 
or 28 days 
after last 
dose if ET 
Day 176 
(±3 days) 
or 35 days 
after last 
dose if ET29 
Day 197 
(±3 days) 
or 56 days 
after last dose 
if ET29 
Day 225 
(±3 days) 
or 84 days 
after last 
dose if ET 
Informed consent 
X 
Demographics 
X 
X 
Medical History 
X 
X 
Prior and Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body weight and height2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
10 or 12-lead ECG4 
X 
Complete Physical Exam5 
X 
Symptom-Directed Physical Exam6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Baseline Diet Assessment7 
X 
Baseline Diet Compliance8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Previous Treatments and Procedure 
Review 
X 
Stool for Ova and Parasite9 
X 
Stool antigen test for H. pylori32 
X 
ePRO Activation and Training10 
X 
ePRO Questionnaire (will include 
Additional Questions)11 
< 
Complete electronically 1 time daily 
- 
> 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
<------------------------ Complete electronically on Screening Day 19, Study Day 7, Study Day 28, and Study Day 225 or ET ----------------------------- > 
CCI 
CCI 
<---------------------------------- Complete electronically on Study Day 7, Study Day 28 and Study Day 225 or ET ------------------------------------------ > 
EGD + colonoscopy with 
Biopsy12,14 
X 
X 


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Table 1 
Schedule of Assessments cont. 
 
 
 
 
 
 
Assessment Description 
Screening 
(21–45 days) 
Treatment Period 
(20 weeks) 
Follow-Up Period30 
(12 weeks) 
Baseline1 
Prior to 
Day 1 
Dose 1 
Day 12 
Day 8 
(±2 days) 
Day 15 
(±2 days) 
Dose 2 
Day 29 
(±3 days) 
Dose 3 
Day 57 
(±3 days) 
Dose 4 
Day 85 
(±3 days) 
Dose 5 
Day 113 
(±3 days) 
Dose 6 
Day 141 
(±3 days) 
Day 169 
(±3 days) 
or 28 days 
after last 
dose if ET 
Day 176 
(±3 days) 
or 35 days 
after last 
dose if ET29 
Day 197 
(±3 days) 
or 56 days 
after last dose 
if ET29 
Day 225 
(±3 days) 
or 84 days 
after last 
dose if ET 
Blood for CBC with differential21 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Chemistry15,22 
(Screening Chemistry includes 
hCG and FSH) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Serology and 
Strongyloides stercoralis 16 
X 
Blood for Total Serum IgE17 
X 
X 
Blood for PK23 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for ADA24 
X 
X 
X 
X 
X 
X 
X 
Urine for Urinalysis25 
X 
X 
X25 
Dipstick Pregnancy Test26 
X 
X 
X 
X 
X 
X 
X 
X 
Eligibility Assessment 
X 
X 
X 
Premedication: Prednisone19 
X 
Access IRT: Stratification and 
Randomization18 
X 
Access IRT: IP Kit Assignment 
X 
X 
X 
X 
X 
X 
Study Drug Administration20 
X 
X 
X 
X 
X 
X 
Non-serious Adverse Events27 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events28 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Begin OLE period of the study at 
least 1 day after Day 176 Visit 
(if applicable)29, 31 
X 
Day 197 and 
Day 225 visits are 
not applicable for 
OLE patients 


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Table 1 Notes 
ADA: 
Anti-AK002 antibody 
ET: 
Early Termination 
IRT: 
Interactive Response Technology 
 
CBC: 
Complete blood count 
FSH: 
Follicle-stimulating hormone 
ECG: 
Electrocardiogram 
hCG: 
Human Chorionic Gonadotropin 
ePRO:   electronic Patient Reported Outcome 
IP: 
Investigational Product 
PK: 
Pharmacokinetics 
 
1) Baseline screening visit can occur over several days within the screening period. Day 1 can begin as soon as eligibility criteria are met. 
2) At screening, height (in cm) and weight (in kg) will be recorded. Body weight will also be measured on Days 1, 29, 57, 85, 113, 141, and on follow-up Days 176, 197 and 225 
or 28,56, and 84 days after last dose, if ET. Current body weight or body weight from 1 day prior will be used to calculate the amount of AK002/placebo to be mixed with 
NaCl for the appropriate dose to be administered on each infusion day. 
3) Vital signs will be measured at screening, Days 176, 197, and 225 or 28,56 and 84 days after last dose if ET and on all dosing days: within 30 minutes predose, 
15 (±5) minutes after the start of study drug infusion, within 15 minutes following the end of infusion and just prior to discharge. Additional vital signs measurements may be 
collected at the Investigator’s discretion if an IRR occurs. Vital signs including systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate will be 
measured after the patient has been at rest for ≥5 minutes and before any blood draws have been obtained (unless collected for an IRR). 
4) A 10-lead or 12-lead ECG will be obtained at screening before any blood is drawn and after the patient has been in the appropriate position for ≥5 minutes. 
5) 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. 
6) A symptom-directed physical exam (including assessment of possible infusion site reactions) will be performed by the Investigator or designee, as needed, if any symptoms 
are reported. 
7) A baseline diet assessment (Protocol Appendix 3) will be performed using standardized questions. Eating patterns, food avoidance behaviors, and confirmed allergies will be 
captured. 
8) A baseline diet compliance check will be performed at every study visit, except as noted above, and any variances from the baseline diet documented. Patients should maintain 
the baseline diet throughout the study. 
9) Fecal collection kits for ova and parasite test will be provided to patients at screening. Collection kits should be returned to the clinical site within 1 day of collection. Negative 
results must be available prior to randomization. 
10) Activate PRO questionnaire and provide patient with unique username and password. PRO questionnaire should be activated for all patients on screening Day 1. 
11) PRO should be completed around the same time each day. Prior to enrollment, the PRO weekly averages of abdominal pain, nausea, and diarrhea over the screening period 
will be calculated and used to assess eligibility. Weekly average Total Symptom Score (TSS6) will be calculated for eligibility and stratification. Patients will also complete an 
additional question each about dysphagia and constipation daily during the screening period and throughout the study. The additional questions will be completed following 
the PRO questionnaire. 
CCI 
CCI 


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Table 1 Notes cont. 
12) EGD + colonoscopy with biopsy (performed on the same day whenever possible) will include specimens from the gastric mucosa, duodenum, colon and esophagus (as 
applicable). Specimens will be processed by the central laboratory. See the Histology Manual for collection, processing, and shipping details. The specimens will be evaluated 
by a central pathology reader. Additional biopsies will be collected for exploratory analysis. Prior EGD and colonoscopy biopsy samples may be used for eligibility as long as 
they were performed within 45 days of the AK002-021 screening window for the AK002-021 study and were performed and centrally assessed using the same criteria as for 
the AK002-021 study, and there were no changes to EoD therapy following the EGD. 
13) The CCI 
is to be completed electronically by patient, in clinic, prior to any blood draw, physical exam, or vital sign measurements. 
14) See Protocol Appendix 5 for biopsy assessments. The post-treatment EGD + colonoscopy and biopsy assessments will be performed on Day 169 (±3) or 28 (±3) days after last 
dose of study drug if ET. Post-treatment EGD + colonoscopy biopsy results will be blinded to the site. 
15) Blood for baseline chemistry, including hCG and FSH, will be collected during the screening period. Only patients of childbearing potential and post-menopausal women are 
required to have hCG and FSH testing completed. 
16) Blood for serology testing will be collected during screening and will include HBsAg, hepatitis C antibody, anti-HBc, and HIV, as well as Strongyloides stercoralis. 
17) Blood samples for total serum IgE will be collected during screening and on Day 176 or 35 (±3) days after last dose of study drug, if ET. 
18) Stratification based on TSS of <28 or ≥28 will occur. Randomization and stratification will be conducted through the IRT system. 
19) Premedication with 80 mg oral prednisone or approved alternative is required 12–24 hours prior to the first infusion. Premedication prior to the start of the second through 
sixth infusions will only be administered with the prior written approval of the Medical Monitor. 
20) Study drug will be administered as a single peripheral intravenous infusion over at least 4 hours for Dose 1 and at least 1 hour for subsequent doses. Refer to the Pharmacy 
Manual. 
21) Blood for CBC with differential, including absolute blood eosinophil count, will be obtained once during screening, Day 8, Day 15, and once during each follow-up visit or 
ET visit, as well as twice during dosing days just prior to each infusion and 1 hour (±15 minutes) after the end of each infusion. All differential blood counts from Day 1 
(postdose) through the end of the patient’s participation will be blinded to the Sponsor and the site. An unscheduled CBC may be collected at the request of the Safety 
Monitor. 
22) Blood for chemistry will be obtained once during screening and once during each follow-up visit or ET visit as well as predose on dosing days. 
23) Blood for PK will be obtained predose on dosing Days 29, 57, 85, 113, and 141, as well as during screening and on Days 8, 15, 169, 176, 197, and 225 or 28, 35, 56, and 
84 (±3) days after last dose of study drug if ET. 
24) Blood for ADA will be collected at screening and predose on dosing Days 1, 29, 57, and 85, as well as on Day 169 and 225 or 28 (±3) and 84 (±3) days after last dose of study 
drug if ET. The ADA sample will also be collected any time an immunogenicity-related AE occurs. 
25) Urine for standard urinalysis will be obtained at screening, predose on dosing Day 29, ET, and symptom based, as necessary. 


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Table 1 Notes cont. 
26) Urine will be collected for dipstick pregnancy test on all infusion days and on Day 176 and Day 197 or 35 and 56 (±3) days after last dose of study drug, for all patients of 
childbearing potential. Test kits will be supplied by the central laboratory. Tests will be completed on site and evaluated prior to each infusion. 
27) The capture of non-serious AE and AESI will begin after the first dose of study drug has occurred. 
28) The reporting of SAE occurring after signing the informed consent and prior to the first infusion 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 infusion of study drug. For patients participating in the OLE period, AE will be assessed 
and recorded in the CRF of the AK002-021 double-blind treatment period database up until the start of the first open-label infusion, after the Day 176 visit. The AE will be 
recorded in the CRF of the AK002-021 OLE period database beginning with the start of the first open-label infusion after Day 176. 
29) Patients who continue in the OLE period of the study will complete the procedures for Day 176 and may begin open-label dosing in the OLE period of the study, if eligible, 
1 day after completion of the Day 176 visit. In this case, patients will not complete the Day 197 or Day 225 procedures under the double-blind period of the study. 
30) The ET visits should be conducted 28, 35, 56, and 84 (±3) days after last dose of study drug or prior to this, if necessary, to ensure compliance with the visit. If only 1 ET visit 
is possible, EGD + colonoscopy and end-of-study procedures may occur on the same day. If the end-of-study visit occurs more than 35 days after last dose of study drug, then 
perform the visit as soon as possible. The procedures listed under the 28-day and 35-day post-study drug visit will be conducted unless otherwise directed by the Medical 
Monitor. For patients participating in the OLE period, AE and concomitant medications should be collected and recorded in the AK002-021 double-blind treatment period 
database up until the start of the first open-label infusion after the Day 176 visit. This includes prednisone premedication administered after the Day 176 visit of the OLE 
period, which should be recorded in the Concomitant Medications CRF of both the AK002-021 double-blind treatment period database and the AK002-021 OLE period 
database. 
31) The final hematology assessment for the double-blind period of the study must be collected prior to the patient taking prednisone premedication for the first dose of the OLE 
period. Therefore, dosing in OLE must take place at least 1 day after completion of the Day 176. 
32) Stool antigen test for H. pylori will be obtained to confirm no existing active H. pylori infection is present. Fecal collection fecal kits (same container as for ova and parasite 
testing) should be returned to the clinical site within 1 day of collection. Negative results must be available prior to randomization. If H. pylori is detected in tissue biopsies by 
the central pathologist, the patient should be excluded from the trial. In case of a positive test, the patient must be screen failed. After H. pylori treatment and an additional 
6 weeks later, patient may be reconsented and will receive a new patient number. 


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3.2 
Study Treatment 
 
3.2.1 
Treatment, Dose, and Mode of Administration 
Subjects will be randomly assigned through the IRT system to an active 6 doses of AK002 at 
3 mg/kg or placebo. The exact dose will be calculated prior to each infusion and based on current 
subject weight. Study drug will be administered as a single peripheral IV infusion using an 
infusion pump on Days 1, 29 (±3), 57 (±3), 85 (±3), 113 (±3), and 141 (±3). 
 
3.2.2 
Duration of Study 
The total study duration will be approximately 8 months, which includes: 
• 
Screening phase: 21–45 days prior to study drug administration 
• 
Treatment phase: 20 weeks 
• 
Follow-up period: A follow-up period of 84 days (±3) after last dose of study drug. 
• 
Patients who enter the OLE period of the study will participate in the double-blind period of 
Study AK002-021 for 26–32 weeks and will complete the study at least through the Day 
176 visit. 
• 
Patients who enter the OLE period prior to Day 197 will not complete the Day 197 visit or 
Day 225 visit of the double-blind study period but will instead follow the OLE schedule of 
events through Day 373. 
 
3.2.3 
Methods of Assigning Subjects to Treatment Group 
Approximately 80 subjects with active EoD (without EG) will be stratified by baseline TSS. 
Subject will be randomized 1:1 to receive 1 of 2 dose regimens using stratified randomized 
blocks in a double-blind manner. 
• 
6 doses of AK002 at 3 mg/kg administered every 4 weeks 
• 
6 doses of placebo 
 
3.3 
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 
Hypotheses 
The hypothesis to be tested in the study is that AK002 is different from placebo regarding the 2 
co-primary efficacy endpoints of the proportion of subjects with tissue eosinophil response at 
Week 24 and the mean reduction from baseline in TSS at Weeks 23–24. 


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3.5 
Determination of Sample Size 
A total of approximately 80 subjects will be enrolled. 
 
First Co-Primary Endpoint: A sample size of 40 subjects per treatment group will have >90% 
power to demonstrate a greater proportion of histologic responders at Week 24 in AK002 
subjects compared to placebo subjects, assuming the proportions of histologic responders are 0.6 
and 0.1 in AK002 and placebo groups, respectively. 
 
Second Co-Primary Endpoint: A sample size of approximately 40 patients per treatment group 
will provide 80% power to detect a statistically significant difference of 7.4 points between 
AK002 and placebo in the mean reduction from Baseline in TSS at Weeks 23-24, assuming a 
common standard deviation of 12.5 points (AK002-003 data on file). 
 
4. 
Definitions 
 
4.1 
Terminology and Definitions 
Table 2 
Terminology and Definitions 
 
Terminology 
Definition 
Baseline 
Baseline for non-daily assessment (e.g., laboratory tests and CCI  is defined as the 
non-missing value collected most recent to and before the time of the very first dose 
of study drug. This includes lab test collected on Day 1 Predose as an example. 
Baseline Total Symptom Score (TSS) will be the average of the weekly TSS 
collected in the last 2 weeks prior to the first dose. The day before and day of 
colonoscopy will be taken into consideration when computing baseline TSS. 
Completer for the Study 
Subjects who complete at least through the Day 176 visit if continuing to the OLE 
period of the study or Day 225 visit if not continuing to the OLE period of the study. 
Concomitant Medication 
Medication collected on the Prior/Concomitant Medication CRF, with end date 
on/after Study Day 1. Note a Prior Medication may also be a Concomitant 
Medication if the start date is prior to Study Day 1 and end date is on/after Study 
Day 1. 
Enrolled 
Subject who is randomized to a treatment group. 
Newly Initiated Medication Newly initiated medication refers to any medication with a start date ≥ Study Day 1 
Patient-Reported Outcome 
The patient-reported outcome (PRO) questionnaire evaluates 8 different symptoms 
with 10 daily questions for intensity and frequency: 
• Abdominal pain intensity 
• Nausea intensity 
• Vomiting intensity 
• Vomiting frequency 


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Table 2 
Terminology and Definitions cont. 
Terminology 
Definition 
Patient-Reported Outcome 
cont. 
• Diarrhea intensity 
• Diarrhea frequency 
• Fullness before finishing a meal (Early satiety) intensity 
• Loss of appetite intensity 
• Bloating intensity 
• Abdominal cramping intensity 
Each intensity evaluation is scored on a scale of 0=none to 10=worst possible. 
Prior Medication 
Medication collected on the Prior/Concomitant Medication CRF, with start date 
prior to Study Day 1. 
PRO Total Symptom Score 
Total symptom score (TSS) is the sum of 6 (abdominal pain, abdominal cramping, 
bloating, nausea, early satiety, and loss of appetite) weekly average symptom 
intensity scores. 
Study Day 
Study Day 1 is defined as the date on which a subject took the first dose of study 
drug. Other study days are defined relative to Study Day 1. 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 Drug 
AK002 or placebo administered by IV infusion. 
Study Week 
Study Week for PRO analysis is defined as 7 days a week starting from the day of 
first dose (Day 1). 
Tissue Eosinophil 
Responder in EoD 
Mean duodenal eosinophil count ≤15 cells/hpf in 3 highest duodenal hpf. 
Treatment-emergent 
Adverse events reported in the clinical database with a date of onset on or after the 
start date of the first dose of the study drug. 
Treatment Responder 
Subject with >30% improvement in TSS from baseline and mean eosinophil count 
≤15 cells/hpf in 3 highest duodenal hpf. 
 
4.2 
Target of Estimation 
The estimand (target of estimation) for Protocol AK002-020 is: 
In subjects with EoD, what is the between group (AK002 vs. Placebo) difference in the 
proportion of tissue eosinophil responders at Week 24, and the group difference in TSS 
from baseline to Weeks 23–24 as measured by the patient-reported outcome (PRO) 
questionnaire. 
 
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 must have a histological diagnosis of EoD. A key 
aspect of eligibility is that subjects must have a weekly average score of abdominal pain, nausea, 
or diarrhea ≥3 on the PRO questionnaire (score from 0–10) for at least 2 weeks of screening and 
a weekly average TSS of ≥10 for at least 2 weeks of screening. 
 
The protocol specifically excluded conditions including inflammatory bowel disease, other 
chronic inflammatory diseases in the colon (with the exception of eosinophilic colitis), celiac 
disease, achalasia, or esophageal surgery as these were identified at the time of study conception 
as potential confounders to interpretation of the degree of change in TSS based on overlap in 
symptomatology and several of the symptom-based components of the TSS PRO. The intent of 
this study criteria was as an exclusionary measure for any condition that may interfere with the 
interpretation of the assessment of efficacy based on the TSS instrument however the list of 
exclusionary conditions was not exhaustive and other concomitant conditions that could likewise 
confound interpretation and detection of a treatment effect may not have been fully appreciated 
(see exclusion criterion 7 and Appendix 5 in study protocol). 
 
Subsequently, a supplementary analysis of data from a recent study, AK002-016, focused on 
identification of baseline characteristics which correlate with degree of change in TSS6 at Weeks 
23-24. This examination identified eight variables (age, gender, duodenal eosinophil counts, 
diarrhea frequency, history of IBS, abdominal pain, esophageal eosinophils per hpf >6, and 
history of IBS in combination with diarrhea intensity ≥3) that most influenced the degree of 
change of the TSS endpoint. Two of the variables (esophageal eosinophils per hpf >6, and 
history of IBS in combination with diarrhea intensity ≥3) potentially reflect other disease states 
(IBS, GERD or even active EoE) that could potentially impact multiple symptom components of 
TSS6. To ensure these two variables do not compromise the capacity to detect the treatment 
effect with symptoms of EoD as measured by the TSS questionnaire, the primary comparison of 
AK002 vs placebo will be conducted on the Evaluable population defined as subjects who do not 
exhibit any of the following conditions at baseline: 
1. 
>6 eosinophils per hpf in at least one esophageal site. 
2. 
Documented history of irritable bowel syndrome and baseline diarrhea intensity ≥3. 
 
4.2.2 
Variables of Interest (or Endpoint) to be Obtained for Each Subject 
that is Required to Address the Scientific Question 
The co-primary endpoints to be obtained for each subject in this study to address the scientific 
question are tissue eosinophil responders (as defined in Table 2) at Week 24 and change in TSS 
from baseline to Weeks 23–24 as measured by the PRO questionnaire. 


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4.2.3 
Treatment 
AK002 or placebo administered to subjects on Days 1, 29, 57, 85, 113, and 141. 
 
4.2.4 
Intercurrent Events 
The events below are considered intercurrent events (ICE) confounding with the efficacy 
outcomes. 
• 
Premature discontinuation from the study 
• 
Use of prohibited/restricted medication 
 
Further clarification and handling of ICE including prohibited/rescue medications is detailed in 
Appendix 2. 
4.2.5 
Strategy for Handling Intercurrent Events 
For the analysis of the study product estimand, tissue eosinophil values and TSS will be counted 
as non-responders for binary variables and set to missing for continuous outcomes from the point 
when an ICE occurs. The estimand will provide an answer to the question that is crucial to 
individual subjects: 
“If I take this study medication as part of my treatment regimen, without adding any further 
medications that may impact the underlying disease or exit the study prematurely, what 
improvements in histology and PRO symptoms might be anticipated after 24 weeks?” 
 
4.2.6 
Summary Measure of the Estimand 
• 
Percent (and 95% CI) of subjects having tissue eosinophil response at Week 24 in the 
AK002 and Placebo treatment groups and the absolute difference (and 95% CI) in the 
percent response between treatments. 
• 
Least squares mean (LSM) (and standard error [SE]) of change from baseline to the average 
of Weeks 23–24 TSS and the between treatment difference in the AK002 and placebo 
treatment groups LSM. LSM and SE derived from mixed model repeated measures 
(MMRM) model. 
 
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. 


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All CRF 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 
• 
Percentage: 1 decimal place generally, or 2 decimal places for <0.1%, or no decimal places 
for 0% and ≥100% 
• 
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. 


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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 should 
some of the assumptions underlying the proposed analyses not be met. Reason for departure 
from the planned methods will be documented as 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. These may provide biased results if the assessment is performed early or late. 
Therefore, assessments will be slotted into analysis windows to allow summaries to be 
performed for subjects with similar study drug exposure. The analysis window is constructed by 
the medians of 2 target study days of the adjacent planned visits. 
 
Table 3 
Analysis Window Rules for CCI 
Visit Description 
Window 
Baseline 
On or Prior to Day 1 Predose 
Day 1 
Predose on infusion Day 1 
Day 29 
Day 1 Postdose to Day 42 
Day 57 
Day 43 to Day 70 
Day 85 
Day 71 to Day 98 
Day 113 
Day 99 to Day 126 
Day 141 
Day 127 to Day 158 
Day 176 
Day 159 to Day 186 
Day 197 
Day 187 to End of Study 


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Table 4 
Analysis Window Rules for Vital Sign and Laboratory Tests 
Visit Description 
Window 
Baseline 
On or Prior to Day 1 Predose 
Day 1 
Day 1 Postdose 
Day 15 
Day 2 to Day 22 
Day 29 
Day 23 to Day 42 
Day 57 
Day 43 to Day 70 
Day 85 
Day 71 to Day 98 
Day 113 
Day 99 to Day 126 
Day 141 
Day 127 to Day 158 
Day 176 
Day 159 to 186 
Day 197 
Day 187 to End of Study 
 
Table 5 
Analysis Window Rules for PK Concentration and ADA 
Visit Description 
Window 
Baseline 
On or Prior to Day 1 Predose 
Day 8 
Day 1 Postdose to Day 11 
Day 15 
Day 12 to Day 22 
Day 29 
Day 23 to Day 42 
Day 57 
Day 43 to Day 70 
Day 85 
Day 71 to Day 98 
Day 113 
Day 99 to Day 126 
Day 141 
Day 127 to Day 154 
Day 169 
Day 155 to Day 172 
Day 176 
Day 173 to Day 186 
Day 197 
Day 187 to Day 210 
Day 225 
Day 211 to End of Study 


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Table 6 
Analysis Window Rules for Blood Histamine and Urinalysis 
Visit Description 
Window 
Baseline 
On or Prior to Day 1 Predose 
Day 1 
Predose on Day 1 
Day 29 
Day 1 Postdose to Day 42 
Day 57 
Day 43 to Day 70 
Day 85 
Day 71 to Day 98 
Day 113 
Day 99 to Day 126 
Day 141 
Day 127 to Day 158 
Day 176 
Day 159 to Day 186 
Day 197 
Day 187 to End of Study 
 
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. 
 
5.3 
Adjustment for Covariates 
Efficacy analyses will be adjusted for baseline values and randomization stratum using 
ANCOVA, MMRM, or Cochran-Mantel-Haenszel tests, where applicable. 
 
5.4 
Handling of Dropouts, Missing Data, and Data Discrepancies 
 
5.4.1 
Missing Duodenal Tissue Eosinophil Count at Week 24 
Eosinophil counts will be set to missing if they are collected after subjects have experienced ICE. 
Subject with missing Week 24 tissue eosinophil count for any reason will be imputed with the 
eosinophil count collected from the postbaseline unscheduled visit prior to missing. If no 
eosinophil count is collected postbaseline, the subject will be considered treatment failure for 
tissue eosinophil response. 
5.4.2 
Missing Daily PRO Scores at Weeks 23–24 
PRO daily scores will be set to missing if they are collected after subjects have experienced ICE. 
We note that the day before and day of colonoscopy will be taken into consideration when 
computing baseline and Week 24 TSS scores. For the endpoints of change in the weekly average 
of PRO TSS, when ≥4 of 7 daily scores are available, the weekly average score will be 
calculated using the available daily scores. (See Appendix 1 for justification of allowing weekly 


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average being calculated from ≥4 daily scores.) This calculation implies the missing daily scores 
are the same as the mean of the non-missing daily scores. When ≥4 daily scores are missing, the 
weekly score will be set to missing. For the calculation of the average PRO TSS over Weeks 23- 
24, if ≥1 weekly score is missing, the biweekly average of Weeks 23–24 will be considered 
missing. 
 
Missing average of Weeks 23–24 TSS will be imputed using the Markov Chain Monte Carlo 
(MCMC) method. Baseline tissue eosinophil count and PRO TSS will be included along with the 
average biweekly PRO TSS (W01_02, W03_04, W05_06, …, W21_22, W23_24) in the 
multivariate distribution construction. The imputation will be carried out for each treatment 
group separately and will be executed multiple (50) times (MI). The purpose of MI is to account 
for the imputation variability in the parameter estimates. An example of the SAS code for this 
imputation follows. 
 
proc mi data=TSS seed=1357986420 nimpute=50 
out=TSS_IMMPUTED ; 
by TRTMT ; 
mcmc chain=multiple impute=full initial=em nbiter=200 niter=100 ; 
var B_EOS B_TSS TSS_W01_02 TSS_W03_04 
... TSS_W21_22 TSS_W23_24 ; 
run ; 
 
After the imputation, the least squares mean (LSM) and standard error (SE) are derived from the 
conventional ANCOVA from each imputed data set. 
 
These LSM and SE are synthesized to derive the imputation variability-adjusted LSM and SE for 
each treatment group and for the between treatment difference. These synthesized LSM and SE 
are then used in the hypothesis test for the between treatment difference. An example of the SAS 
code for the synthesized LSM comparisons between treatment is as follows. 
 
ods output ParameterEstimates=LSMDIF ; 
proc mianalyze data=DIFF alpha=0.05 ; 
modeleffects LSM ; 
stderr SE ; 
run ; 
 
5.4.3 
Missing or Partial Dates of Adverse Events or Concomitant Medications 
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 


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events with missing relationship to study drug will be included in the “Related” category for the 
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 
Interim Analysis 
No interim analysis is planned. 
 
5.6 
Timing of Data Analyses 
The database lock will occur after all subjects complete participation in the double-blind period 
of the study. 
 
For the database lock, applicable EDC data will be locked in order 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. 
• 
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 35 sites. Analysis of site effect will be based on analysis 
centers. Analysis centers will be formed in such a way that there are sufficient subjects per 


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pooled analysis center for the assessment of study site effects. Pooling of study sites by 
geographic location is described below: 
• 
Analysis Center 1: Massachusetts, Connecticut, Rhode Island, New York, New Jersey, 
Pennsylvania, District of Columbia, Maryland, Maine, Vermont, Delaware, and New 
Hampshire 
• 
Analysis Center 2: Virginia, West Virginia, South Carolina, Georgia, Mississippi, Florida, 
Alabama, Louisiana 
• 
Analysis Center 3: North Carolina, Tennessee, Ohio, Michigan, Indiana, Kentucky 
• 
Analysis Center 4: South Dakota, Arkansas, Minnesota, Wisconsin, North Dakota, Illinois, 
Missouri, Iowa, Texas, Oklahoma, Kansas, Nebraska, Wyoming, Colorado 
• 
Analysis Center 5: Utah, New Mexico, Arizona, California, Oregon, Washington, Idaho, 
Hawaii, Alaska, Montana, Nevada 
 
5.8 
Multiple Comparisons/Multiplicity Adjustment 
To control for the family-wise type-I error rate, the following testing procedures will be 
implemented: 
 
Test each co-primary efficacy endpoint at 2-sided α=0.05 level. 
• 
If p≤0.05 for both co-primary endpoints, then reject the null hypothesis that AK002 is no 
different from placebo and accept the alternative hypothesis that AK002 is superior to 
placebo in reducing tissue eosinophil count and TSS score. 
• 
If p≤0.05 for both co-primary endpoints, the hypothesis tests for the secondary endpoints 
will proceed in the prespecified order. 
• 
If p>0.05 for either co-primary endpoint, the null hypothesis is accepted. No hypothesis test 
will be performed for the secondary endpoints. 
• 
The issue of multiplicity of secondary endpoints will be handled by statistical testing of 
these outcomes in a hierarchical fashion. The order of secondary endpoints is described in 
Section 2.2. If at any point during the analysis of the secondary endpoints, the statistical test 
is not significant at 2-sided α=0.05 level, the hypothesis testing procedure will stop. AK002 
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 subgroups. Subgroups to be considered are: 


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• 
Gender (Male, Female) 
• 
Age (<65, ≥65) 
• 
Race (White, Non-White) 
• 
IgE (<45, ≥45) 
 
6. 
Statistical Analysis 
 
6.1 
Analysis Populations 
The population of “all screened subjects” 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 is defined as subjects who were randomized and 
received at least 1 dose of the study drug. 
 
6.1.4 
Per Protocol Analysis Population 
The per protocol (PP) population will include the Evaluable population (see Section 6.1.5) who 
have received at least 1 dose of study drug and did not have major protocol violations potentially 
interfering with the efficacy assessment. The PP exclusion criteria will be specified prior to the 
database lock and unblinding. 
 
6.1.5 
Primary Analysis Population 
The primary efficacy analysis population is the Evaluable Population defined as all randomized 
subjects who have received at least 1 infusion of study drug, and at study entry do not exhibit 
any of the following criteria: 
1. 
>6 eosinophils per hpf in at least one esophageal biopsy at baseline 
2. 
Documented history of irritable bowel syndrome and baseline diarrhea intensity ≥3. 
• 
The complement to the Evaluable population will be referred to as the Excluded population. 
It is worth remarking that for this study, if a subject has a history of concomitant EoE, or if 


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esophagus looks suspicious for EoE or other condition, or if patient is symptomatic on 
screening dysphagia question, quantified by a score of >3 on the dysphagia question on at 
least 1 day during screening, then the following is undertaken: 
− A set of 2 fragments is collected from the distal esophagus 
− A set of 2 fragments is collected from the mid-proximal esophagus 
− Up to 2 extra specimens may be collected if there are any additional areas of interest. 
• 
A count of >6 eosinophils per hpf in at least one esophageal site will be considered 
diagnostic of at least having esophageal eosinophilia for the purposes of the study and in 
cases where there is a history of EoE this could reflect active eosinophilic esophagitis 
although fulfillment of the diagnostic criteria for that condition may not be certain (see 
Appendix 5 for details). 
Analysis will be conducted on the complement population, referred to as Excluded Population, 
and is planned as exploratory. In addition, for completeness purposes, analysis will be conducted 
on the mITT population to show what the study results would have been on all the subjects prior 
to removing those with confounding conditions outlined above. 
 
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 all enrolled subjects. 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 all enrolled subjects. 


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6.3 
Protocol Deviations 
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 8.1) 
• 
Non-compliance with study inclusion or exclusion criteria 
• 
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 
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 PP population will be listed with reasons for exclusion. 
 
6.4 
Demographics and Baseline Subject Characteristics 
Descriptive statistics for subject characteristics and baseline values 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 Evaluable, Excluded, mITT, and PP populations. 
6.5 
Baseline Disease Characteristics 
Baseline disease characteristics including demographics, weight, blood eosinophils 
(≥500 cells/µL), IgE, IgE category (<45/≥45), history of atopic dermatitis, functional GI 
symptoms, history of EG and/or EoD, duodenal eosinophils (per 3hpf in EoD), TSS total score at 
baseline, PRO symptom scores, and baseline elevated esophageal eosinophils histologic criteria 
will be included in the subject data listing. 
6.6 
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). 
 
6.7 
Electrocardiogram 
A listing of electrocardiograms (ECG) overall interpretation at screening visit will be provided. 


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6.8 
Pregnancy Test 
A listing of pregnancy test results will be provided. 
 
6.9 
Baseline Diet 
A listing of baseline and on-study diet assessment and compliance will be provided. 
 
6.10 
Treatments 
 
6.10.1 
Treatment Compliance and Extent of Exposure 
Summaries of treatment compliance and exposure to AK002 will be based on the safety 
population. 
 
Duration of treatment exposure is defined as the total number of days a subject is exposed to the 
study treatment. This will be calculated for each subject by taking the difference between the 
date of last dose minus the date of first dose, plus 1 (date of last dose – date of first dose +1). 
Duration of exposure will be summarized using descriptive statistics (n, mean, standard 
deviation, median, minimum, and maximum). 
 
Treatment compliance is defined as the number of infusions that subjects received divided by 
6 (i.e., total number of infusions expected) × 100%. Treatment compliance will be summarized 
descriptively. In addition, an overall compliance that includes adherence to treatment 
administration schedule and any interruptions will be included in the data listing. 
 
The treatment infusion information (length, volume, rate, and interruption) will be included in 
the subject data listing. 
 
6.10.2 
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 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 


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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. A separate data listing will include 
subjects who have received prohibited medications. 
6.11 
Analysis of Primary Efficacy Endpoints 
To assist the data interpretation, all ICE will be listed with pertinent subject information (subject 
ID, date of last infusion, ICE start/stop day, nature of ICE (reason for treatment/study 
discontinuation if applicable, description of AE, description of prohibited/restricted medication), 
baseline tissue eosinophil count and TSS, and most recent tissue eosinophil count and 2-week 
average of TSS). A summary table will be created to present number of subjects (n, %) by 
treatment group: 
• 
Subjects with any ICE 
− Subjects by ICE category 
 
6.11.1 
Analysis of the First Co-Primary Endpoint 
The first co-primary endpoint will be analyzed using the imputed data set (Section 5.4.1). 
Fisher’s exact test (primary analysis) will be conducted comparing AK002 with placebo for the 
proportion of tissue eosinophil responders. Proportion of responders and the associated 95% 
confidence interval will be presented for each treatment group. The between group difference 
and the associated 95% confidence interval will also be computed and presented. A sample SAS 
code is as follows. 
* 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 TRTAN ; 
run; 
 
* COMPUTE 95% EXACT CONFIDENCE INTERVAL AND FISHERS EXACT P-VALUE FOR 
BETWEEN TREATMENT DIFFERENCE ; 
ods output FishersExact=PVAL(where=(name1='XP2_FISH')) 
RiskDiffCol2=DIFF(where=(row='Difference') ; 
proc freq data=ADEF ; 
table TRTPN*RESP / riskdiff(cl=exact) exact ; 
run ; 


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6.11.2 
Sensitivity Analysis of the First Co-Primary Endpoint 
Sensitivity analysis may be carried out using the Cochran-Mantel-Haenszel (CMH) test stratified 
by the randomization stratification factor (baseline TSS [<28 vs. ≥28] to assess robustness of the 
Fisher’s exact test results. 
 
A sample SAS code for the pairwise comparison 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 TSS_STRAT*TRTP*RESP / cmh commonriskdiff 
(cl=NEWCOMBE) ; 
run ; 
 
The rationale for specifying the Fisher’s exact test as the primary analysis as opposed to 
specifying the CMH is because when a stratum has 100% response for 1 treatment group and 0% 
response for another treatment group, the CMH test may lose efficiency or not be computable. 
This is evident from the Phase 2 study outcome. 
 
6.11.3 
Subgroup Analysis of the First Co-primary Endpoint 
Analysis comparing AK002 and placebo will use the Fisher’s exact test for each of the 
subgroups defined in Section 5.9. 
 
6.11.4 
Analysis of the Second Co-Primary Endpoint 
The second co-primary endpoint will be analyzed using mixed model for repeat measures 
(MMRM) with treatment, week, treatment-by-week interaction, and baseline TSS-by-week 
interaction as fixed factors, gender, and baseline TSS (continuous) as covariates, and study site 
(with pooling by geographic location) as random effect. If the model does not converge with 
pooled sites as a random effect, it will be simplified with pooled site as a fixed effect. 
 
The weekly TSS score is calculated as the average of the daily TSS scores. Weekly TSS will be 
set to missing if >3 daily TSS are missing. Baseline TSS score will be the average of the last 
2 weeks of daily TSS collected prior to the first infusion. The model variance-covariance matrix 
will be unstructured. However, if computation does not converge, the matrix will take the form 
of Toeplitz, autoregressive, or compound symmetry, whichever converges first. A sample of the 
SAS code for MMRM analysis is provided as below: 


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proc mixed data=tss method=reml; 
class TRTMT USUBJID AVISITN ANALYSIS_CENTER GENDER; 
model CHG= B_TSS TRTMT AVISITN ANALYSIS_CENTER GENDER 
TRTMT*AVISITN B_TTS*AVISITN / DDFM=KR; 
REPEATED AVISITN / SUBJECT=USUBJID (TRTMT) TYPE=UN; 
RANDOM ANALYSIS_CENTER; 
LSMEANS TRTMT*AVISITN / PDIFF CL; 
ESTIMATE 'PBO VS. AK002 at WEEKS 23-24' TRTMT -1 1 
TRTMT*AVISITN 0 0 0 0 0 0 0 0 0 0 0 -1 
0 0 0 0 0 0 0 0 0 0 0 1 / CL; 
 
RUN; 
 
Where TRTMT = planned treatment group in numeric (1 = placebo, 2 = AK002); AVISITN = 
time point (i.e., Weeks 1-2, Weeks 3-4, …, Weeks 23-24. 
 
6.11.5 
Sensitivity Analyses of the Second Co-Primary Endpoint 
The two sensitivity analyses planned below are constructed based on the already imputed 
biweekly data set from Section 5.4.2. 
 
The first sensitivity analysis is based on the placebo-based pattern-mixture model for the missing 
data imputation under the missing not at random (MNAR) assumption. In this model, subjects 
from the active treatment group after the ICE are assumed to behave like the subjects from the 
placebo group. Their missing data are imputed using the response profile from the placebo 
subjects who have similar baseline covariates and prior response trajectory. The sample SAS 
code follows. 
/*Step 1: Achieve Monotone Missing Data Pattern */ 
 
 
proc mi data=tss seed=135791 nimpute=50 out=mono; 
var B_EOS B_TSS TSS_W01_02 TSS_W03_04 ... 
TSS_W21_22 
TSS_W23_24; 
MCMC impute=monotone nbiter=200 niter=100; 
By TRTMT; 
run ; 
 
/*Step 2: Achieve Control-Based Copy-Reference Imputation */ 
 
 
proc mi data=mono seed=135791 nimpute=50 out=outm1; 
class TRTMT; 
by _imputation_; 
var TRTMT B_EOS B_TSS TSS_W01_02 TSS_W03_04 ... 
TSS_W21_22 
TSS_W23_24; 


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monotone reg; 
mnar model(TSS_W01_02 TSS_W03_04 ... TSS_W21_22 TSS_W23_24 / 
modelobs=(TRTMT='0')); * CODE 0 IS FOR PLACEBO GROUP ; 
run ; 
 
/*Step 3: Run MMRM Analysis on Imputed Data */ 
 
proc mixed data=tss method=reml; 
class TRTMT USUBJID AVISITN ANALYSIS_CENTER GENDER; 
model CHG= B_TSS TRTMT AVISITN ANALYSIS_CENTER GENDER 
TRTMT*AVISITN B_TTS*AVISITN / DDFM=KR; 
REPEATED AVISITN / SUBJECT=USUBJID (TRTMT) TYPE=UN; 
RANDOM ANALYSIS_CENTER; 
LSMEANS TRTMT*AVISITN / PDIFF CL; 
ESTIMATE 'PBO VS. AK002 at WEEKS 23-24' TRTMT -1 1 
TRTMT*AVISITN 0 0 0 0 0 0 0 0 0 0 0 -1 
0 0 0 0 0 0 0 0 0 0 0 1 / CL; 
ODS OUTPUT PARAMETERESTIMATES=PESTIMATES; 
RUN; 
 
/*Step 4: Combining estimates from each imputed data set */ 
 
proc mianalyze data=PESTIMATES; 
modeleffects ESTIMATE; 
stderr stderr; 
by label; 
ods output PARAMETERESTIMATES=miparm; 
run ; 
 
 
The second sensitivity analysis is based on ANCOVA using the imputed data set (Section 5.4.2). 
The LS mean, SE, and 95% CI for each treatment group and for the between group difference 
will be derived from ANCOVA with treatment as factor, baseline PRO TSS (continuous) as 
covariates. The hypothesis test for the treatment effect will be carried out by the F-test. The 
synthesizing method will be used to combine the results from multiple imputations. The sample 
SAS code follows. 
/** ANCOVA by imputation **/ 
ods output diffs=diffs lsmeans=lsm; 
proc mixed data=ADIMP1 method=reml; 
where PARAMCD=’TSS6’ and ATPT=’Weeks 23-24’; 
by IMPUTED1; 
class gender analysis_center TRT01P; 
model CHG=gender analysis_center BASE TRT01P; 
lsmeans TRT01P / diff; 
quit; 
ods output close; 


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/** Combine LS Means (by treatment and difference) **/ 
data lsmdiff; 
set lsm diffs(in=d); 
if d then trt01p='DIFF'; 
run; 
 
proc sort; 
by trt01p; 
run; 
 
 
/** Synthesized results **/ 
ods output ParameterEstimates=SYNDIF; 
proc mianalyze data=LSMDIFF alpha=0.05; 
by trt01p; 
modeleffects ESTIMATE; 
stderr STDERR; 
run; 
 
ods output close; 
 
6.11.6 
Supplementary Analyses 
Analysis of Section 6.11.2 will be repeated for the Per Protocol population. 
 
Additional analysis will investigate the treatment effect on PRO TSS change from baseline in the 
subgroups defined in Section 5.9. This analysis will use MMRM similarly to the primary 
analysis (Section 6.11.2). 
 
Empirical cumulative distribution function (eCDF) of the change from baseline in TSS will be 
plotted by treatment group to demonstrate consistency of the treatment effect. 
 
6.12 
Analysis of Secondary Efficacy Endpoints 
 
6.12.1 
Change in Tissue Eosinophil Count 
For subjects who provide duodenal biopsy, the calculation will be based on the average count of 
the highest readings from the respective mucosa at baseline and Day 169 (Week 24). The change 
in tissue eosinophil count from baseline to Day 169 will be analyzed using ANCOVA with 
treatment as factor, baseline eosinophil counts, baseline PRO TSS as covariates. The LSM, SE, 
and 95% CI for individual treatment groups, and LSM, SE, 95% CI, and p-value for the between 
treatment difference will be presented. 
 
6.12.2 
Proportion of Subjects Achieving Peak Duodenal Intraepithelial Eosinophil Count 
of ≤1 Cell/hpf 
This endpoint will be analyzed using the Fisher’s exact test similar to the analysis for the first 
co-primary endpoint (Section 6.11.1). 


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6.12.3 
Proportion of Treatment Responders 
Treatment responder is defined as >30% improvement in TSS and mean eosinophil count ≤15 
cells/hpf in 3 highest duodenal hpf. This endpoint will be analyzed using Fisher’s exact test 
similar to Section 6.11.1. 
 
6.12.4 
Proportion of Subjects with ≥50% Reduction and ≥70% Reduction in 
TSS from Baseline to Weeks 23–24 
These 2 endpoints will be analyzed using the CMH test stratified by the randomization 
stratification factor. 
 
6.12.5 
Change in Weekly TSS Over Time 
Prior to the analysis, the missing weekly TSS scores will be imputed similarly to the imputation 
for the missing biweekly PRO TSS scores (Section 5.4.2). The imputed data sets will be 
analyzed using the mixed model for repeat measures (MMRM) similar to the analysis for the 
second co-primary endpoint. 
 
The rationale for using the MMRM model is that this analysis is appropriate assuming subjects 
with missing data behave similarly to other subjects in the same treatment group. Having 
included in the model baseline symptom score (TSS), and response trajectory prior to missing, it 
is reasonably to believe that the missing data are either completely at random (MCAR) or at 
random (MAR) in this setting. In another words, if missing mechanism is not MCAR, it is likely 
explainable by the above model covariates and response trajectory. 
 
6.13 
Analysis of Exploratory Endpoints 
 
6.13.1 
Change in 
Change from baseline in the number of 
in 
will be analyzed using 
 
 
6.13.2 
Change in 
Change from baseline in 
summary (including domain scores) will be analyzed using 
 
 
similar to Section 6.12.5. 
 
6.13.3 
Change in 
Change from baseline in 
will be analyzed using 
CCI 


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CCI 
CCI 
6.13.4 
Change in 
Changes in 
 
from baseline compared to post-treatment in the 
will be analyzed using 
 
 
6.13.5 
CCI 
Change from baseline in CCI 
will be analyzed using the CCI 
similar to the CCI 
• 
• 
• 
• 
• 
• 
 
CCI 
the analysis variable, will be based on the CCI 
and calculated as the CCI 
to establish a CCI 
The data will be analyzed by CCI 
at 
Weeks 23-24. The sample SAS code follows. 
 
• 
CCI 
CCI 
CCI 
CCI 
CCI 
CCI 
CCI 
CCI 
CCI 
, the analysis variable, will be the CCI 
(defined as CCI 
and calculated as the CCI 
to establish a CCI 
Analyzed in a CCI 


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CCI 
6.13.6 
Methods for 
and 
and 
are described in a separate analysis plan. 
 
6.14 
Analysis of Pharmacokinetic Endpoint 
The analysis of the PK concentration will be based on the Safety population. AK002 
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. 
 
6.15 
Safety Analyses 
 
6.15.1 
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. 
 
For summaries by relationship to study drug, “possibly related” will be combined with “related”, 
and “unlikely/remotely related” will be combined with “not related.” When multiple AE are 
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. 
CCI 
CCI 
CCI 


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• 
Overview of TEAE to include 
− Number (%) of subjects who reported at least 1 TEAE 
− 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). 
 
6.15.2 
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. 


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Shift tables will be presented, in which, lab test results at baseline and post-baseline visit will be 
classified into below (<LLN), within (≥LLN and ≤ULN), and above (>ULN) normal ranges. 
Subject incidences (n and %) will be presented for the shift from baseline to the post-baseline 
visits. 
 
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. 
 
6.15.3 
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. 
6.15.4 
Electrocardiogram 
Incidence of the Investigator’s overall assessment (normal, abnormal – not clinically significant, 
and abnormal – clinically significant) will be summarized. 
 
6.15.5 
Physical Examination 
New or worsening symptoms in the symptom-directed physical exams will be included in the 
by-subject data listing. 
 
6.15.6 
Analysis of Anti-Drug Antibody 
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 are 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. 


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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: 
• 
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. 


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9. 
Appendices 
 
9.1 
Appendix 1: Effect of Missing Data on the Weekly Mean of TSS 
 
9.2 
Appendix 2: Intercurrent Events 
 
9.3 
Appendix 3: List of Tables, Figures, and Listings 
 
9.4 
Appendix 4: Example SAS Codes 


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9.1 
Appendix 1: Effect of Missing Data on the Weekly Mean of TSS 
Following the FDA’s suggestion for the evaluation of the missing daily diary effect on the 
weekly mean of TSS score, data from the Phase 2 study are extracted. The Phase 2 study has 
diaries collected daily over 14 weeks of the treatment period. A simulation study was conducted 
examining the changes in standard error by the number of missing daily diaries that were 
randomly created. The step are as follows. 
1) 
A complete date set is created in which a subject week is kept only if the week has all 
7 daily diaries. This data set is at the subject-day level. 
2) 
For each week in the complete data set, 1 of the 7 daily diaries is randomly set to missing. 
This creates a data set with 1 day per week missing. 
3) 
Step 2 is repeated for 2 of the 7 daily diaries are randomly set to missing to create a data set 
with 2 day per week missing. 
Finally, a data set is created with 6 days per week are randomly set to missing. 
 
4) 
For each of the 7 data sets (0 day/week missing, 1 day/week missing, …, 6 days/week 
missing), daily diaries are averaged to derive the weekly mean for each subject at each 
week. 
5) 
Weekly means of the diaries are further averaged across all subjects to derive the 
population means and population standard error of the diaries for each week. 
6) 
Steps 2 through 5 are repeated 500 times. Each time, the daily diaries are randomly set to 
missing. 
7) 
The 500 weekly population standard errors from Step 6 are averaged and presented in the 
table below. 
 
As expected, the standard error increases as the number of missing daily diaries increases, 
indicating the estimate of weekly TSS mean becomes less accurate. However, the increase in the 
standard error does not exceed 2% when allowing 3 out of 7 daily diaries missing, and does not 
exceed 4% when allowing 4 out of 7 daily diaries missing. 


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Table 7 
Standard Errors for the Mean Weekly TSS Diaries by Number of 
Daily Diaries Missing Averaged over 500 Simulations 
Week 
Number of Daily Diaries Missing 
0 Day 
1 Day 
2 Days 
3 Days 
4 Days 
5 Days 
6 Days 
1 
3.092 
3.100 
3.115 
3.132 
3.166 
3.232 
3.405 
2 
2.917 
2.923 
2.929 
2.941 
2.964 
3.003 
3.102 
3 
3.070 
3.081 
3.088 
3.095 
3.125 
3.198 
3.321 
4 
2.862 
2.868 
2.874 
2.881 
2.894 
2.926 
2.994 
5 
3.111 
3.118 
3.122 
3.134 
3.149 
3.187 
3.293 
6 
3.135 
3.137 
3.147 
3.154 
3.170 
3.191 
3.279 
7 
3.039 
3.045 
3.054 
3.067 
3.093 
3.140 
3.283 
8 
3.842 
3.846 
3.849 
3.858 
3.871 
3.884 
3.959 
9 
2.854 
2.869 
2.874 
2.899 
2.932 
3.021 
3.176 
10 
2.823 
2.829 
2.840 
2.845 
2.857 
2.886 
3.010 
11 
2.997 
3.002 
3.010 
3.008 
3.037 
3.069 
3.148 
12 
2.656 
2.661 
2.671 
2.689 
2.691 
2.731 
2.842 
13 
2.864 
2.879 
2.886 
2.905 
2.950 
3.011 
3.208 
14 
2.388 
2.402 
2.414 
2.437 
2.474 
2.580 
2.795 
Source: K:\AK002-016\planning\MissingOnSE.sas 08MAR2020 


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9.2 
Appendix 2: Intercurrent Events 
 
A. 
Use of any of the following prohibited medications during the course of the study as 
described 
1) 
Immunosuppressive or immunomodulatory drugs (e.g., IL-5 modulators, i.e., 
benralizumab, reslizumab, mepolizumab; IL-4 and IL-13 antagonists, i.e., dupilumab; 
calcineurin inhibitors, i.e., cyclosporin, tacrolimus;, mTOR inhibitors, i.e., sirolimus, 
everolimus; anti-metabolites, i.e., azathioprine, methotrexate, 6-mercaptopurine, 
leflunomide, mycophenolate mofetil; alkylating agents, i.e., cyclophosphamide; TNF 
inhibitors, i.e., infliximab, adalimumab; anti-IgE antibodies, i.e., omalizumab; and 
eosinophil-depleting drugs, i.e., pramipexole. 
a) 
Use at any point during the study. 
2) 
Glucocorticoids 
a) 
Initiation of any course of treatment or single use of systemic or swallowed 
corticosteroids at a dose of >10 mg/day prednisone or equivalent starting at 
Week 21 and through the end of Week 24. This does not include use of 
corticosteroids given as pre-infusion prophylaxis or treatment of IRR. 
 
B. 
Use of restricted medications outside the protocol-defined specifications 
1) 
Glucocorticoids 
a) 
Discontinuation of a previously stable dose of systemic or swallowed 
corticosteroids (≤10 mg/day prednisone or equivalent) after the screening period. 
b) 
Initiation of a new course of systemic or swallowed corticosteroids (≤10 mg/day 
prednisone or equivalent) following the screening period and continuing to at 
least study Week 21 (within 2 weeks of efficacy assessment at Weeks 23 and 24). 
2) 
Proton Pump Inhibitors 
a) 
Discontinuation of a previously stable dose of an oral PPI after the screening 
period and before the end of Week 24. 
b) 
Initiation or increase in the dose of an oral PPI following the screening period 
and continuing to at least study Week 21 (within 2 weeks of efficacy assessment 
at Weeks 23 and 24). 
3) 
Sodium cromolyn 
a) 
Discontinuation of a previously stable dose of sodium cromolyn after the 
screening period and before the end of Week 24 


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b) 
Initiation or increase in the dose of sodium cromolyn following the screening 
period and continuing to at least study Week 22 (within 1 week of efficacy 
assessment at Weeks 23 and 24). 
 
C. 
Discontinuation of Investigational Medical Product 
1) 
Discontinuation of study agent due to: 
a) 
Infusion-related reaction 
b) 
Subject withdrawal 
c) 
Meeting study withdrawal criteria (Protocol Section 13.10) 
 
Per protocol, subjects are required to remain on stable doses of either PPI or corticosteroids 
(≤10 mg prednisone equivalent per day) throughout the course of the study if they are on a stable 
dose during the screening period. Because of the potential impact of corticosteroids and PPI on 
both histologic assessment of tissue eosinophil levels as well as subject reported GI symptoms, 
subjects must meet the entry requirements for both histology and symptom burden (TSS6) if they 
are on any of these medications at screening and therefore must remain on a stable dose 
throughout the study in order to meaningfully interpret any change from baseline during the 
evaluation phase. Conversely, subjects starting these medications due to unforeseen medical 
necessity following the screening period and remaining on them through a time point sufficiently 
close to the evaluation period to potentially impact assessment of symptoms and/or histologic 
assessments will be considered as intercurrent events. For PPI and corticosteroids (≤10 mg/day 
prednisone or equivalent) a conservative washout period is estimated at 2 weeks, and therefore, 
continuation of a new course of therapy beyond Week 21 could be considered as a potential ICE. 
Sodium cromolyn is a mast cell stabilizer and could potentially impact reported symptoms in a 
similar way to 1 of the mechanisms of action of AK002. As such, discontinuation of a previously 
stable dose of sodium cromolyn after the screening period and before the end of Week 24 could 
be considered as a potential ICE. Likewise, the initiation or increase in the dose of sodium 
cromolyn following the screening period and continuing to at least study Week 22 (within 
1 week of efficacy assessment at Weeks 23 and 24) could be considered as a potential ICE. It is 
estimated that 1 week would be a sufficient washout period for the effects of sodium cromolyn. 
Antihistamines are unlikely to impact histologic assessments in the study but could have slight 
impact in some symptoms depending on the type, dose, and duration of use. As such, subjects are 
required to stay on stable doses of antihistamines if they are taking them at the time of screening 
and to remain on them through completion of the study. Due to unforeseen medical 
circumstances and acknowledging that some subjects may have concurrent allergic conditions, 
the use of these medications by some subjects during the study is anticipated. 


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9.3 
Appendix 3: 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 (Evaluable Population) 
 
Table 14.1.1d 
Subject Disposition and Reason for Discontinuation (Excluded Population) 
 
Table 14.1.1e 
Subject Disposition and Reason for Discontinuation 
(Per Protocol Population) 
Table 14.1.2 
Major Protocol Deviations 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 (Evaluable Population) 
Table 14.1.5c 
Demographics and Baseline Characteristics (Excluded Population) 
Table 14.1.5d 
Demographics and Baseline Characteristics (Per Protocol Population) 
Table 14.1.6a 
Medical History by System Organ Class and Preferred Term: Subject 
Incidence (Safety/MITT Population) 
Table 14.1.6b 
Medical History by System Organ Class and Preferred Term: Subject 
Incidence (Evaluable Population) 
Table 14.1.7.1 
Study Drug Exposure (Safety Population) 
Table 14.1.7.2 
Study Drug Exposure (Safety Population) 
Table 14.1.7.3 
Duration of Treatment Exposure and Compliance (Safety Population) 
 
Table 14.1.8.1a 
Prior Medications by Anatomic Therapeutic Chemical Classification and 
Preferred Term: Subject Incidence (Safety Population) 


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Table 14.1.8.1b 
Prior Medications by Anatomic Therapeutic Chemical Classification and 
Preferred Term: Subject Incidence (Evaluable 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 14.1.11a 
Baseline Eosinophil and 
Counts (MITT Population) 
Table 14.1.11b 
Baseline Eosinophil and 
Counts (Evaluable Population) 
Table 14.1.12a 
Baseline Dysphagia Severity Score (MITT Population) 
Table 14.1.12b 
Baseline Dysphagia Severity Score (Evaluable Population) 
 
Table 14.1.13a 
Baseline Subject Reported Outcome Total and Symptom Scores 
(MITT Population) 
Table 14.1.13b 
Baseline Subject Reported Outcome Total and Symptom Scores 
(Evaluable Population) 
Table 14.1.14 
Baseline Vital Signs (MITT Population) 
 
Table 14.1.15a 
Subject Incidence of Intercurrent Events (MITT Population) 
Table 14.1.15b 
Subject Incidence of Intercurrent Events (Evaluable Population) 
Table 14.2.1.1a 
Tissue Eosinophil Responder at Week 24 – Primary and Sensitivity 
Analysis (Evaluable Population) 
Table 14.2.1.1b 
Tissue Eosinophil Responder at Week 24 – MITT Population 
Table 14.2.1.1c 
Tissue Eosinophil Responder at Week 24 – Excluded Population 
Table 14.2.1.2.1 
Tissue Eosinophil Responder at Week 24 by Gender (Evaluable Population) 
 
Table 14.2.1.2.2 
Tissue Eosinophil Responder at Week 24 by Age Group 
(Evaluable Population) 
Table 14.2.1.2.3a 
Tissue Eosinophil Responder at Week 24 by Baseline Peripheral Eosinophil 
Count Subgroup (Evaluable Population) 


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Table 14.2.1.2.3b 
Tissue Eosinophil Responder at Week 24 by Race (Evaluable Population) 
 
Table 14.2.1.2.3c 
Tissue Eosinophil Responder at Week 24 by IgE Group (Evaluable 
Population) 
Table 14.2.2.1a 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – Primary Analysis – MMRM (Evaluable Population) 
Table 14.2.2.1a 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – MMRM (MITT Population) 
Table 14.2.2.1c 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – MMRM (Excluded Population) 
Table 14.2.2.2 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – Sensitivity Analysis 1 – Weekly TSS Due to ICE are 
Replaced/Imputed Using Placebo-Based Pattern-Mixture Model Multiple 
Imputation (Evaluable Population) 
Table 14.2.2.3 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – Sensitivity Analysis 2 – Weekly TSS Due to ICE are 
Replaced/Imputed Using Multiple Imputation by the MCMC Method 
(Evaluable Population) 
Table 14.2.2.4 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – MMRM (Per Protocol Population) 
Table 14.2.2.5.1 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores by Gender – MMRM (Evaluable Population) 
Table 14.2.2.5.2 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores by Age Group – MMRM (Evaluable Population) 
Table 14.2.2.5.3a 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores by Baseline Peripheral Eosinophil Count Subgroup – MMRM 
(Evaluable Population) 
Table 14.2.2.5.3b 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores by Race – MMRM (Evaluable Population) 
Table 14.2.2.5.3c 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores by Baseline IgE Group – MMRM (Evaluable Population) 


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Table 14.2.3 
Change from Baseline to Week 24 Tissue Eosinophil Count 
(Evaluable Population) 
Table 14.2.4 
Subjects Achieving Duodenal Intraepithelial Eosinophils Count ≤1 cell/hpf 
(Evaluable Population) 
Table 14.2.5 
Subjects Achieving Tissue Eosinophil and TSS Treatment Response 
(Evaluable Population) 
Table 14.2.6 
Subjects with ≥50% Reduction and ≥70% Reduction in TSS from Baseline 
to Weeks 23-24 (Evaluable Population) 
 
Table 14.2.7 
Change from Baseline in Weekly TSS from Week 1 Through Week 24 
Using MMRM (Evaluable Population) 
Table 14.2.8 
Change from Baseline to Week 24 CCI 
(Evaluable Population) 
 
Table 14.2.9.1 
Change from Baseline in 
– Physical Component Summary 
(Evaluable Population) 
Table 14.2.9.2 
Change from Baseline in 
– Mental Component Summary 
(Evaluable Population) 
Table 14.2.10 
Change from Baseline in 
(Evaluable Population) 
 
Table 14.2.11.1 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.11.2 
Change from Baseline in Weekly 
(Evaluable 
Population) 
Table 14.2.11.3a 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.11.3b 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.11.4a 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.11.4b 
Change from Baseline in Weekly 
(Evaluable Population) 
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Table 14.2.11.5 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.11.6 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.11.7 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.11.8 
Change from Baseline in Weekly 
(Evaluable Population) 
 
Table 14.2.12 
Severity of Dysphagia at Baseline and Post-Baseline (Evaluable Population) 
 
Table 14.2.13 
Morphological Assessment of Gastric Biopsies by Sydney System 
(Evaluable Population) 
Table 14.2.14 
Morphological Assessment of Duodenal Biopsies by Marsh Scale 
Classification (Evaluable Population) 
Table 14.2.15 
Change from Baseline in Body Weight (Evaluable Population) 
Table 14.2.16 
Total Serum IgE Concentration (Evaluable Population) 
Table 14.2.17a 
Subject Incidence of Positive Anti-Drug (AK002) Antibody (ADA) Test 
(Safety Population) 
Table 14.2.17b 
Subject Incidence of Positive Anti-Drug (AK002) Antibody (ADA) Test 
(Evaluable Population) 
Table 14.3.1.1a 
Overview of Treatment-Emergent Adverse Events (Safety Population) 
Table 14.3.1.1b 
Overview of Treatment-Emergent Adverse Events (Evaluable Population) 
Table 14.3.1.2a 
Treatment-Emergent Adverse Events by Preferred Term: Subject Incidence 
(Safety Population) 
Table 14.3.1.2b 
Treatment-Emergent Adverse Events by Preferred Term: Subject Incidence 
(Evaluable Population) 
 
 
Table 14.3.1.3a 
Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term: Subject Incidence (Safety Population) 
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Table 14.3.1.3b 
Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term: Subject Incidence (Evaluable Population) 
Table 14.3.1.4a 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Maximum Severity: Subject Incidence (Safety Population) 
Table 14.3.1.4b 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Maximum Severity: Subject Incidence (Evaluable Population) 
Table 14.3.1.5a 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Relationship to Study Drug: Subject Incidence 
(Safety Population) 
 
Table 14.3.1.5b 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Relationship to Study Drug: Subject Incidence 
(Evaluable Population) 
 
Table 14.3.1.6a 
Treatment-Emergent Adverse Events Leading to Study Drug 
Discontinuation by System Organ Class and Preferred Term: Subject 
Incidence (Safety Population) 
Table 14.3.1.6b 
Treatment-Emergent Adverse Events Leading to Study Drug 
Discontinuation by System Organ Class and Preferred Term: Subject 
Incidence (Evaluable Population) 
Table 14.3.1.7a 
Treatment-Emergent Serious Adverse Events by System Organ Class and 
Preferred Term: Subject Incidence (Safety Population) 
Table 14.3.1.7b 
Treatment-Emergent Serious Adverse Events by System Organ Class and 
Preferred Term: Subject Incidence (Evaluable Population) 
Table 14.3.1.8a 
Treatment-Emergent Adverse Events of Special Interest by System Organ 
Class and Preferred Term: Subject Incidence (Safety Population) 
Table 14.3.1.8b 
Treatment-Emergent Adverse Events of Special Interest by System Organ 
Class and Preferred Term: Subject Incidence (Evaluable 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) 


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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 
Cumulative Distribution Function Plot of Change from Baseline in Average 
of Weeks 23-24 TSS (Evaluable Population) 
Figure 2 
P-value from Between-Treatment Comparison in Weeks 23-24 TSS – 
Tipping Point Analysis (Evaluable 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 Diet Assessment (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 16.2.2.1.1 Esophago-Gastro-Duodenoscopy (EGD) Biopsy Finding 
(Safety Population) 
Listing 16.2.2.1.2 Duodenal biopsy assessments (Safety Population) 
Listing 16.2.2.1.3 Esophageal biopsy assessments (Safety Population) 
Listing 16.2.2.2a Eosinophilic Gastritis and Gastroenteritis Questionnaire – Question Text 
(Safety Population) 
Listing 16.2.2.2b 
Eosinophilic Gastritis and Gastroenteritis Questionnaire – Daily Score 
(Safety Population) 
Listing 16.2.2.2c Eosinophilic Gastritis and Gastroenteritis Questionnaire – Weekly Score 
(Safety Population) 
Listing 16.2.2.3 
Eosinophilic Gastritis Endoscopic Reference Score (EGERS) 
(Safety Population) 
Listing 16.2.2.4a 
Questionnaire – Question Text 


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Listing 16.2.2.4b 
Listing 16.2.2.4c 
Listing 16.2.2.5a 
Listing 16.2.2.5b 
 
Listing 16.2.3.1.1 
 
Listing 16.2.3.1.2 
 
Listing 16.2.3.1.3 
 
Listing 16.2.3.1.4 
 
Listing 16.2.3.1.5 
 
Listing 16.2.3.2.1 
 
Listing 16.2.3.2.2 
 
Listing 16.2.3.2.3 
 
Listing 16.2.3.2.4 
 
 
Listing 16.2.3.2.5 
 
Listing 16.2.3.2.6 
 
Listing 16.2.3.2.7 
 
Listing 16.2.3.3.1 
 
Listing 16.2.3.3.2 
 
Listing 16.2.3.4.1 
 
Listing 16.2.3.4.2 
 
Listing 16.2.3.5 
 
Listing 16.2.3.6 
 
Listing 16.2.3.7.1 
Questionnaire – Individual Questions (ITT Population) 
Questionnaire – Domain Scores (ITT Population) 
Intensity of Symptoms Questionnaire – Question Text (Safety Population) 
 
Intensity of Symptoms Questionnaire – Individual Scores 
(Safety Population) 
All Adverse Events (Safety Population) 
Serious Adverse Events (Safety Population) 
Adverse Events with Outcome of Death (Safety Population) 
 
Adverse Events Leading to Study Drug Discontinuation (Safety Population) 
Adverse Events of Special Interest (Safety Population) 
Clinical Laboratory Tests-Hematology (Safety Population) 
Clinical Laboratory Tests – Blood Chemistry (Safety Population) 
Clinical Laboratory Tests – Urinalysis (Safety Population) 
Clinical Laboratory Tests – Diagnostic Immunology/Molecular Biology 
(Safety Population) 
Clinical Laboratory Tests – Endocrinology (Safety Population) 
Clinical Laboratory Tests – Parasitology (Safety Population) 
Pre-Infusion Blood Collection (Safety Population) 
Substance Use – Alcohol Consumption at Screening (Safety Population) 
Urine Pregnancy Test (Safety Population) 
Study Drug Administration (Safety Population) 
Study Drug Accountability (Safety Population) 
Vital Signs (Safety Population) 
Subject Body Size (Safety Population) 
 
12-Lead ECG Intervals at Baseline (Safety Population) 
CCI 


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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 16.2.3.10.1 Morphological Assessment of Gastric Biopsies by Sydney System 
(Safety Population) 
Listing 16.2.3.10.2 Morphological Assessment of Duodenal Biopsies by Marsh Scale 
Classification (Safety Population) 
Listing 16.2.3.10.3 Morphological Assessment of Esophageal Biopsy (Safety Population) 
Listing 16.2.3.11 
Serum Concentrations of IgE (Safety Population) 


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9.4 
Appendix 4: Example SAS Codes 
 
/** Multiple Imputation **/ 
proc mi data=TSS seed=1357986420 nimpute=50 out=TSS_IMPUTED1 ; 
by TRTMT ; 
mcmc chain=multiple impute=full initial=em nbiter=200 niter=100 ; 
var B_EOS B_TSS TSS_W01_02 TSS_W03_04... TSS_W21_22 TSS_W23_24 ; 
quit; 
/** Recalculate change from baseline **/ 
data tss_imputed2; 
set tss_imputed1; 
chg=tss_w23_24 - b_tss; 
run; 
 
proc sort data=tss_imputed2 out=tss_imputed; 
by _imputation_; 
run; 
 
/** ANCOVA by imputation **/ 
ods output diffs=diffs lsmeans=lsm; 
proc mixed data=tss_imputed method=reml; 
by _imputation_; 
class analysis center gender TRTMT; 
model CHG= analysis_center genderB_TSS TRTMT; 
lsmeans TRTMT / diff; 
quit; 
ods output close; 
 
/** Combine LS Means (by treatment and difference) **/ 
data lsmdiff; 
set lsm diffs(in=d); 
if d then trtmt='DIFF'; 
run; 
 
proc sort;by TRTMT;run; 
 
 
/** Synthesized results **/ 
ods output ParameterEstimates=SYNDIF; 
proc mianalyze data=LSMDIFF alpha=0.05; 
by TRTMT; 
modeleffects ESTIMATE; 
stderr; 
run ; 
ods output close;