Clinical trial NCT04322604
Conditions: Eosinophilic Gastritis Eosinophilic Duodenitis
Keywords: Eosinophil Eosinophilic Eosinophilic gastrointestinal disorders EGID EG EGE Eosinophilic Gastritis Eosinophilic Gastroenteritis Eosinophilic Duodenitis
Sponsor: Allakos Inc.
Start date: 2020-06-18; Completion date: 2022-01-12
Enrollment: 181 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 patients with moderately to severely active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (formerly referred to as Eosinophilic Gastroenteritis) who have an inadequate response with, lost response to, or were intolerant to standard therapies

Detailed description:

Arms: arm 1: Placebo arm 2: Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): a first dose of 1 mg/kg followed by 5 monthly doses of 3 mg/kg.
Interventions: intervention 1: lirentelimab (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: 
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975 Island Drive, Suite 201, Redwood City, CA 94065
Page 1 of 127
Clinical Research Protocol AK002-016
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 Gastritis and/or Eosinophilic Duodenitis (formerly 
referred to as Eosinophilic Gastroenteritis) Who Have an Inadequate Response 
with, Lost Response to, or Were Intolerant to Standard Therapies
Protocol Number
AK002-016
Version and Date
Original
30 September 2019
Amendment 1
18 March 2020
Amendment 2
07 August 2020
Amendment 3
20 April 2021
Amendment 4
26 October 2021
Investigational Product
AK002 (lirentelimab)
Study Phase
3
Sponsor
Allakos Inc., 975 Island Drive, Suite 201
Redwood City, CA 94065 USA
Medical Monitor
Name:
 MD
Telephone:
Email:
Approval:
MD, MBA
Date
Confidentiality Statement
This confidential information about an investigational product is provided for the exclusive use 
of Investigators of this product and is subject to recall at any time. The information in this 
document may not be disclosed unless federal or state law or regulations require such disclosure. 
Subject to the foregoing, this information may be disclosed only to those persons involved in the 
study who have a need to know, with the obligation not to further disseminate this information. 

	
PPD
PPD
PPD
PPD
PPD
PPD
SIGN


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 2 of 127 
Confidential 
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: 
AK002-016 
IND: 
135158 
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 Gastritis and/or Eosinophilic 
Duodenitis (formerly referred to as Eosinophilic Gastroenteritis) Who 
Have an Inadequate Response with, Lost Response to, or Were Intolerant 
to Standard Therapies 
Original Protocol: 
30 September 2019 
Amendment 1:  
18 March 2020 
Amendment 2:  
07 August 2020 
Amendment 3:  
20 April 2021 
Amendment 4:  
26 October 2021 
 
Investigator Printed Name: _____________________________________________ 
 
Investigator Signature: 
_____________________________________________ 
 
Date: 
_____________________________________________ 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 3 of 127 
Confidential 
Table of Contents 
Clinical Research Protocol AK002-016 ........................................................................................1 
Investigator Protocol Agreement..................................................................................................2 
Table of Contents ...........................................................................................................................3 
List of Tables ..........................................................................................................................9 
List of Abbreviations ............................................................................................................10 
1. 
Protocol Synopsis ................................................................................................................14 
2. 
Background .........................................................................................................................28 
2.1 
Siglec-8 and AK002 .................................................................................................28 
2.2 
Overview of Nonclinical Studies .............................................................................28 
2.3 
Overview of Clinical Studies ...................................................................................29 
2.4 
Eosinophilic Gastrointestinal Disorders ...................................................................31 
3. 
Rationale for Study and Dose Selection ...........................................................................32 
4. 
Study Objectives .................................................................................................................33 
4.1 
Primary Objective ....................................................................................................33 
4.2 
Secondary Objectives ...............................................................................................33 
4.3 
Exploratory Objectives .............................................................................................34 
4.4 
Safety Objectives ......................................................................................................34 
4.5 
Target of Estimation .................................................................................................34 
4.5.1 
Population Targeted by the Scientific Question ........................................35 
4.5.2 
Variables of Interest (or Endpoint) Required to Address the Scientific 
Question .....................................................................................................35 
4.5.3 
Treatment ...................................................................................................35 
4.5.4 
Intercurrent Events .....................................................................................35 
4.5.5 
Strategy for Handling Intercurrent Events .................................................35 
4.5.6 
Summary Measures ....................................................................................36 
5. 
Study Design .......................................................................................................................36 
5.1 
Study Overview ........................................................................................................36 


 
Protocol AK002-016 
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5.2 
Schedule of Events ...................................................................................................38 
6. 
Criteria for Evaluation ......................................................................................................44 
6.1 
Safety Endpoints ......................................................................................................44 
6.2 
Pharmacokinetic Endpoints ......................................................................................44 
6.3 
Efficacy Endpoints ...................................................................................................44 
6.3.1 
Primary Efficacy Endpoints .......................................................................44 
6.3.2 
Secondary Efficacy Endpoints ...................................................................45 
6.3.3 
Exploratory Efficacy Endpoints .................................................................45 
7. 
Patient Selection .................................................................................................................46 
7.1 
Number of Patients ...................................................................................................46 
7.2 
Study Population ......................................................................................................46 
7.3 
Inclusion Criteria ......................................................................................................46 
7.4 
Exclusion Criteria .....................................................................................................47 
7.5 
Safety Evaluations ....................................................................................................49 
8. 
Prior and Concurrent Medications ..................................................................................49 
8.1 
Prohibited Medications ............................................................................................50 
8.2 
Allowed Medications ...............................................................................................50 
9. 
Study Treatment .................................................................................................................51 
9.1 
Formulation of Test Product and Placebo ................................................................51 
9.2 
Study Drug Packaging and Labeling ........................................................................51 
9.3 
Supply of Study Drug to the Investigational Site .....................................................51 
9.4 
Study Drug Dosage/Dosage Regimen ......................................................................51 
9.5 
Preparation of Study Drug ........................................................................................52 
9.6 
Study Drug Administration ......................................................................................52 
9.7 
Study Drug Storage ..................................................................................................53 
9.8 
Study Drug Accountability .......................................................................................53 
10. 
Patient Numbering, Stratification, Randomization, and Blinding ................................53 
10.1 
Patient Numbering ....................................................................................................53 


 
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Strat ificati o n a n d Ra n d o mizati o n .............................................................................5 4  
1 0. 3  
Bli n di n g  ....................................................................................................................5 5  
1 0. 4  
Brea ki n g t he Bli n d  ...................................................................................................5 6  
1 1.  
St u d y Pr oce d ures a n d G ui deli nes  .....................................................................................5 6  
1 1. 1  
Dietar y a n d Lif est yl e Restricti o ns  ............................................................................5 7  
1 1. 2  
P har mac o d y na mic/ Efficac y -R elate d Pr oce d ures  .....................................................5 7  
1 1. 2. 1  
E G/ E o D P R O Q uesti o n naire ......................................................................5 7  
1 1. 2. 2  
 ..................................................................................5 7  
1 1. 2. 3  
 
1 1. 2. 4  
Es o p ha g o -Gastr o -D u o de n osc o p y wit h Bi o ps y  ..........................................5 8  
1 1. 2. 5  
C o m plete Bl o o d C o u nt wit h Differe ntial  ...................................................5 9  
1 1. 2. 6  
Baseli ne Diet Assess me nt  ..........................................................................5 9  
1 1. 2. 7  
Pre vi o us Treat me nts Re vie w  .....................................................................5 9  
1 1. 3  
Safet y -R elate d Pr oce d ures  .......................................................................................6 0  
1 1. 3. 1  
C o nc o mita nt Me dicati o ns  ..........................................................................6 0  
1 1 . 3. 2 
C o m plete P h ysi cal E x a mi nati o n  ................................................................6 0  
1 1. 3. 3  
B o d y Wei g ht a n d Hei g ht  ...........................................................................6 0  
1 1. 3. 4  
St o ol Sa m ple f or O va a n d Parasite  ............................................................6 0  
1 1. 3. 5  
S y m pt o m -Direct e d P h ysi cal E x a mi nati o n  .................................................6 1  
1 1. 3. 6  
Electr ocar di o gra m  ......................................................................................6 1  
1 1. 3. 7  
Vital Si g ns  ..................................................................................................6 1  
1 1. 4  
Cli nical La b orat or y Meas ure me nts  ..........................................................................6 1  
1 1. 5  
Bl o o d C he mistr y Pr ofile  ...........................................................................................6 2  
1 1. 5. 1  
Pre g n a nc y T est a n d F olli cle -Sti m ulati n g H or m o ne  ...................................6 3  
1 1. 5. 2  
Uri nal ysis  ...................................................................................................6 3  
1 1. 5. 3  
Ser ol o g y  .....................................................................................................6 3  
1 1. 5. 4  
A nti -A K 0 0 2 A nti b o dies  .............................................................................6 4  
1 1. 5. 5  
Bl o o d f or P har m ac o ki netics a n d St ora ge  ...................................................6 4  
1 1. 5. 6  
Bl o o d f or Hista mi ne a n d Tr y pt ase  .............................................................6 4  
C CI
C CI


 
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11.5.7 
Blood for IgE .............................................................................................64 
11.5.8 
Blood for Strongyloides stercoralis ...........................................................64 
11.5.9 
COVID-19 Testing.....................................................................................65 
11.5.10 Concurrent Screening between AK002-014 and AK002-016 ...................65 
11.5.11 Screening Procedures in AK002-014 Used for AK002-016 Eligibility ....65 
12. 
Evaluations and Procedures by Visit ................................................................................66 
12.1 
Screening Period ......................................................................................................66 
12.2 
Prior to Day 1 ...........................................................................................................67 
12.3 
Day 1 – Randomization/Infusion 1 ..........................................................................68 
12.4 
Day 7 (not a Clinic Visit) .........................................................................................69 
12.5 
Day 8 (±2) ................................................................................................................69 
12.6 
Day 15 (±2) ..............................................................................................................69 
12.7 
Day 28 (not a Clinic Visit) .......................................................................................69 
12.8 
Day 29 (±3) – Infusion 2 ..........................................................................................70 
12.9 
Day 57 (±3) –  Infusion 3 .........................................................................................71 
12.10 Day 85 (±3) – Infusion 4 ..........................................................................................72 
12.11 Day 113 (±3) – Infusion 5 ........................................................................................73 
12.12 Day 141 (±3) – Infusion 6 ........................................................................................74 
12.13 Day 169 (±3) or 28 (±3) Days after Last Dose of Study Drug if ET – 
Follow-up EGD ........................................................................................................75 
12.14 Day 176 (±3) or 35 (±3) Days after Last Dose of Study Drug if ET – 
Follow-up Visit 1 .....................................................................................................76 
12.15 Day 197 (±3) or 56 (±3) Days after Last Dose of Study Drug if ET – 
Follow-up Visit 2 .....................................................................................................77 
12.16 Day 225 (±3) or 84 (±3) Days after Last Dose of Study Drug if ET .......................78 
13. 
Adverse Event Reporting and Documentation ................................................................78 
13.1 
Adverse Events .........................................................................................................78 
13.2 
Serious Adverse Events ............................................................................................79 
13.3 
Adverse Events of Special Interest ...........................................................................80 


 
Protocol AK002-016 
Amendment 4 
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13.4 
Infusion-Related Reactions ......................................................................................80 
13.5 
Anaphylaxis ..............................................................................................................81 
13.6 
Evaluating Adverse Events and Serious Adverse Events ........................................81 
13.6.1 
Establishing Diagnosis ...............................................................................81 
13.6.2 
Assessment of Intensity .............................................................................82 
13.6.3 
Assessment of Causality to Study Drug.....................................................82 
13.6.4 
Assessment of Causality to Study Procedure.............................................83 
13.6.5 
Action Taken ..............................................................................................84 
13.6.6 
Assessment of Outcome .............................................................................84 
13.7 
Adverse Event Reporting Procedures.......................................................................84 
13.7.1 
All Adverse Events ....................................................................................84 
13.7.2 
Serious Adverse Event Reporting ..............................................................84 
13.7.3 
Pregnancy Reporting ..................................................................................86 
13.7.4 
AESI Reporting ..........................................................................................86 
13.8 
Medical Monitoring ..................................................................................................87 
13.9 
Independent Data Monitoring Committee ................................................................87 
13.10 Study Withdrawal Criteria .......................................................................................87 
13.11 Study Stopping Rules ...............................................................................................87 
14. 
Discontinuation and Replacement of Patients .................................................................88 
14.1 
Definition of Study Completion ...............................................................................88 
14.2 
Early Discontinuation of Study Drug .......................................................................88 
15. 
Statistical Methods and General Considerations ............................................................89 
15.1 
Sample Size ..............................................................................................................89 
15.2 
Analysis Populations ................................................................................................89 
15.3 
Patient Disposition ...................................................................................................90 
15.4 
Demographic and Baseline Characteristics ..............................................................90 
15.5 
Study Drug Exposure ...............................................................................................90 
15.6 
Efficacy Analysis .....................................................................................................90 


 
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15.6.1 
Primary Efficacy Endpoint Analysis .........................................................90 
15.6.2 
Secondary Efficacy Endpoint Analysis .....................................................91 
15.6.3 
Exploratory Analysis .................................................................................92 
15.7 
Safety Analysis .........................................................................................................93 
15.7.1 
Treatment Emergent Adverse Events ........................................................93 
15.7.2 
Anti-Drug Antibodies ................................................................................94 
15.7.3 
Clinical Laboratory Assessments ...............................................................94 
15.7.4 
Vital Signs ..................................................................................................94 
15.7.5 
ECG............................................................................................................94 
15.7.6 
Physical Exam ............................................................................................94 
15.7.7 
Concomitant Medications ..........................................................................94 
15.8 
Patient Confidentiality ..............................................................................................94 
16. 
Data Collection, Retention, and Monitoring ....................................................................95 
16.1 
Data Collection Instruments .....................................................................................95 
16.2 
Data Management Procedures ..................................................................................95 
16.3 
Data Quality Control and Reporting ........................................................................95 
16.4 
Database Lock/Disclosure of Randomization Code .................................................95 
16.5 
Archiving of Data .....................................................................................................96 
16.6 
Availability and Retention of Investigational Records ............................................96 
16.7 
Monitoring ................................................................................................................97 
17. 
Administrative, Ethical, and Regulatory Considerations ...............................................97 
17.1 
Protocol Amendments ..............................................................................................97 
17.2 
Independent Ethics Committees/Institutional Review Boards .................................98 
17.3 
Informed Consent Form ...........................................................................................98 
17.4 
Publications ..............................................................................................................99 
17.5 
Clinical Study Registration ......................................................................................99 
17.6 
Payment to Patients ..................................................................................................99 
17.7 
Investigator Responsibilities ....................................................................................99 


 
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Refere nces  .........................................................................................................................1 0 1  
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A p pe n dices  ........................................................................................................................1 0 3  
1 9. 1  
A p pe n di x 1: P R O Q uesti o n naire  ............................................................................1 0 4  
1 9. 2  
A p pe n di x 2: 
 ...............................................1 0 7  
1 9. 3  
A p pe n di x 3: Baseli ne Di et Assess me nt  .................................................................1 1 3  
1 9. 4  
A p pe n di x 4: C o m m o n Ter mi n ol o g y Criteri a f or A d verse E v e nts v. 5. 0  ...............1 1 4  
1 9. 5  
A p pe n di x 5: E G D Hist ol o g y  ..................................................................................1 1 5  
1 9 . 6 
A p pe n di x 6: Sa m ps o n’s Criteria of A na p h yl a xis  ...................................................1 1 8  
1 9. 7  
A p pe n di x 7: e P R O Teac hi n g T o ol  .........................................................................1 1 9  
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 At o pic C o n diti o ns  ...................................1 2 5  
1 9. 1 1  A p pe n di x 1 1: Pre vi o us Treat me nts Re vie w  ...........................................................1 2 6  
1 9. 1 2  A p pe n di x 1 2: He patitis B a n d He patitis C Ser ol o gical Testi n g Details  ................1 2 7  
1 9. 1 2. 1  He patitis B Testi n g  ..................................................................................1 2 7  
1 9. 1 2. 2  He patitis C Testi n g  ..................................................................................1 2 7  
 
 
 
List of T a bles  
Ta ble 1  
Sc he d ule of Assess me nts  ............................................................................................3 9  
Ta ble 2  
A d verse E v e nt Se verit y per C T C A E  ..........................................................................8 2  
Ta ble 3  
A d verse E v e nt Relati o ns hi p t o St u d y Dr u g  ................................................................8 3  
Ta ble 4  
A d verse E v e nt Relati o ns hi p t o St u d y Pr oce d ure  ........................................................8 3  
Ta ble 5  
He patitis B Refle x Testi n g  ........................................................................................1 2 7  
Ta ble 6  
He patitis C Refle x Testi n g  ........................................................................................1 2 7  
C CI
C CI
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 10 of 127 
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 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical Classification System 
BMI 
Body mass index  
CBC 
Complete blood count 
CDC 
Complement-dependent cytotoxicity 
CDF 
Cumulative distribution function 
CFR 
Code of Federal Regulation 
CI 
Confidence interval 
cm 
Centimeter 
CMH 
Cochran-Mantel-Haenszel (test) 
COVID-19 
Coronavirus disease of 2019 
CS 
Clinically significant 
CTCAE 
Common Terminology Criteria for Adverse Events  
CU 
Chronic Urticaria 
eCDF 
empirical Cumulative Distribution Function 
ECG 
Electrocardiogram(s) 
eCRF 
Electronic Case Report Form 
EG 
Eosinophilic gastritis 
EGD 
Esophago-gastro-duodenoscopy 
EGID 
Eosinophilic gastrointestinal disorders 
EGPA 
Eosinophilic granulomatosis with polyangiitis  
ELISA 
Enzyme-linked immunosorbent assay 
EoD 
Eosinophilic duodenitis (formerly referred to as eosinophilic gastroenteritis) 
EoE 
Eosinophilic esophagitis 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 11 of 127 
Confidential 
EOS 
End of study 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
hCG 
human Chorionic Gonadotropin 
HEENT 
Head, eyes, ears, nose, and throat 
HES 
Hypereosinophilic Syndrome (HES) 
HIPAA 
Health Insurance Portability and Accountability Act 
hpf 
High power field 
ICE 
Intercurrent events 
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 
ITIM 
Immunoreceptor Tyrosine-based inhibitory motif 
ITT 
Intent to treat 
IV 
Intravenous 
kg 
Kilogram 
LLN 
Lower limit of normal 
LSM 
Least squares mean 
MAR 
Missing at random  


 
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C o nfi d e nti al  
M C S  
Me ntal c o m p o ne nt sc ore  
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
m g  
Milli gra m  
MI  
M ulti ple i m p utati o n  
MI T T  
M o difie d I nte nti o n -t o-Treat  
m L  
Milliliter  
m M  
Milli m olar  
M M R M  
Mi xe d m o del f or re p eate 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 olerate d d ose  
Na Cl  
S o di u m c hl ori de  
N CI  
Nati o nal Ca ncer I nstit ute  
N C S  
N ot cli nicall y si g nifica nt  
N O A E L  
N o -o bser ve d -a d verse -effect le vel  
O & P  
O va a n d P arasite (test)  
O R  
O d ds rati o  
O T C  
O ver T he C o u nter  
P C P  
Pri mar y care p h ysicia n  
P C S  
P h ysical c o m p o ne nt sc ore  
P D  
P har mac 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  
P h ysical e xa mi nati o n  
P E F  
P ea k e x pirat or y fl o w  
 
 
 
  
PI D  
P atie nt i de ntificati o n n u m ber 
P K  
P har mac o ki netic(s)  
P P  
P er Pr ot oc ol  
P PI  
Pr ot o n p u m p i n hi bit or  
P R O  
P atie nt re p orte d o utc o me  
S A E  
Seri o us a d verse e ve nt (s) 
S A P  
Statistical A nal ysis Pla n  
S D  
Sta n dar d De viati o n  
C CI
C CI


 
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C o nfi d e nti al  
S E  
Sta n dar d err or  
 
 
Si glec  
Sialic aci d -bi n di n g, i m m u n o gl o b uli n -li ke lecti n 
S O C  
S yste m or ga n class  
T E A E  
Treat me nt -e mer ge nt a d verse e ve nt (s) 
T E A E SI  
Treat me nt -e mer ge nt a d verse e ve nt (s) of si g nifica nt i nterest  
T N F  
T u m or necr osis fact or  
T S S  
T otal S y m pt o m Sc ore  
U B T  
Urea Breat h T est  
U L N  
U p per li mit of n or mal  
U S P  
U nite d States P har mac o peia  
W H O D D  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
w/ v  
W ei g ht/ v ol u me  
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 14 of 127 
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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 Moderately to 
Severely Active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (formerly 
referred to as Eosinophilic Gastroenteritis) Who Have an Inadequate Response 
With, Lost Response to, or Were Intolerant to Standard Therapies 
Sponsor 
Allakos Inc., 975 Island Drive, Suite 201, Redwood City, CA 94065 USA 
Number of Sites 
Approximately 60 clinical centers  
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, 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, healthy volunteers and patients with ISM, CU, severe AC, EG/EoD, EoE, 
and mast cell gastritis have been enrolled in clinical studies. In general, AK002 has 
been well tolerated. The most common treatment-emergent adverse events (TEAE) 
observed were infusion-related reaction (IRR). Most IRR were mild to moderate 
and resolved on their own, with no treatment required; IRR that were serious 
resolved within approximately 24 hours. 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.  


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 15 of 127 
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 and low 
doses, respectively, versus 10% increase for patients on placebo (p<0.0001).  
The reduction of eosinophils was associated with 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 versus 24% reduction in placebo (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 TSS and >75% reduction from baseline in tissue eosinophils) 
versus 5% for placebo treated patients (p<0.0001).  
Approximately 40% of patients had concomitant eosinophilic esophagitis (EoE). 
In those patients, a mean reduction of 95% of eosinophils/high powered field (hpf) 
in esophageal biopsies for AK002 was observed versus no change for placebo. 
Also, 13 of 14 AK002-treated patients (93%) were histologic responders as 
defined by ≤6 eosinophils/hpf versus 1 of 9 placebo-treated patients (11%). 
Dysphagia improved by 53% in AK002-treated patients versus 17% in 
placebo-treated patients.  
More than 90% of patients in the Phase 2 study elected to continue into a 
long-term extension study (AK002-003X). In that study, a starting dose of 1 mg/kg 
was followed by doses of 3 mg/kg. Premedication of 80 mg oral prednisone was 
administered the day before the first and second doses. Using this premedication 
regimen, no IRR were reported on the first infusion of AK002 in the extension 
study. 
Target Disease 
Background and 
Rationale  
EG and/or EoD (previously referred to as EGE) represent what are traditionally 
believed to be rare types of eosinophilic gastrointestinal disorders (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 
(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 eosinophilic duodenitis (EoD) is 
more appropriate.  
The gastrointestinal symptoms are believed to be due to the release of 
inflammatory mediators from activated eosinophils, and likely mast cells. 
Symptoms that are often severe and debilitating commonly include abdominal 
pain, nausea, bloating, early satiety, fullness before finishing a meal, abdominal  


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 1 6  of 1 2 7  
C o nfi d e nti al  
T ar get Dise ase 
B ac k gr o u n d a n d 
R ati o n ale c o nt.  
cra m pi n g, v o miti n g, diarr hea, a n d wei g ht l oss ( Al h m o u d, 2 0 1 6 ; L o pez -Me di na, 
2 0 1 5 ; Ma ns o or, 2 0 1 7 ; Ree d, 2 0 1 5 ). J e nse n (2 0 1 6 ) esti mate d t he pre vale nce of E G 
a n d E o D t o be 6. 3/ 1 0 0, 0 0 0 a n d 8. 4/ 1 0 0, 0 0 0, res pecti vel y (f or patie nts fr o m 1  t o 
6 4  years of a ge). Ma ns o or ( 2 0 1 7 ) esti mate d t he o verall pre vale nce of E G t o be 
5. 1/ 1 0 0, 0 0 0  pers o ns.  
Patie nts ma y als o ha ve c o nc o mita nt at o pic diseases li ke f o o d aller g y, ast h ma 
a n d at o pic der matitis, w hic h f urt her i m pacts q ualit y of life a n d c o ntri b utes t o 
healt h care c osts. A d diti o nall y, 8 % t o 1 0 % of patie nts ha ve c o nc o mita nt E o E 
(J e nse n, 2 0 1 6).  
T here are n o F D A -a p pr o ve d treat me nts f or E G or E o D. C urre nt t hera pies a n d 
disease ma na ge me nt i ncl u des dietar y restricti o n/eli mi nati o n, pr ot o n p u m p 
i n hi bit ors ( P PI), a nti hista mines, s yste mic or s wall o we d c ortic oster oi ds, a n d 
occasi o nal off -la bel use of i m m u n o m o d ulat or y bi ol o gics (Pr ussi n, 2 0 1 4 ; 
Ree d,  2 0 1 5 ; Z ha n g,  2 0 1 7 ).  
Pr ot o n p u m p i n hi bit ors ha ve little t o n o be nefit i n patie nts wit h E G a n d/ or E o D 
des pite re p orts of pr o vi di n g partial be nefit i n s o me patie nts wit h E o E ( Katz,  2 0 1 3 ). 
Restricte d/ele me ntal diets are n ot effecti ve l o n g -ter m treat me nt as t he y re q uire 
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 are ofte n 
n ot rei m b urse d b y i ns ura nce. I n a d diti o n, c o m plia nce is ver y p o or a n d patie nt 
q ualit y of life is greatl y i m pacte d ( Be dell, 2 0 1 8 ; Peters o n, 2 0 1 3 ; Wec hsler, 2 0 1 4 ). 
C ortic oster oi ds, s yste mic or t o pical, ha ve bee n s h o w n t o pr o vi de s y m pt o m relief 
b ut are n ot a p pr o priate f or l o n g -ter m treat me nt d ue t o n u mer o us si de effects a n d 
ass ociate d ris ks i ncl u di n g a dre nal i ns uffici e nc y, b o ne de mi neralizati o n, i ncrease d 
c ha nce of i nfecti o n, oste o p or osis, be ha vi oral iss ues, a n d wei g ht gai n.  
B y mar ke dl y re d uci n g t he n u m ber of bl o o d a n d tiss ue e osi n o p hils a n d i n hi biti n g 
t 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 nts i n hist ol o g y a n d s y m pt o ms i n t hese patie nts.  
Gi ve n t here are n o a p pr o ve d t hera pies f or t hese c hr o nic a n d de bilitati n g diseases, 
bet ter treat me nt o pti o ns are clearl y nee de d t o ma na ge E G a n d E o D. 
R ati o n ale f or 
D ose  Selecti o n  
Base d o n e x perie nce wit h A K 0 0 2 i n healt h y v ol u nteers a n d i n patie nts wit h I S M, 
C U, se vere A C, a n d E G/ E o D, t he pr o p ose d A K 0 0 2 d ose re gi me n of 6 t otal d oses 
is 1 m g/k g f or t he first i nf usi o n, f oll o we d b y 5 d oses of 3 m g/ k g A K 0 0 2, 
a d mi nistere d e ver y 4 wee ks.  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 1 7  of 1 2 7  
C o nfi d e nti al  
R ati o n ale f or 
D ose  Selecti o n 
c o nt. 
N u m ber of P atie nts  A p pr o xi matel y  1 6 0 patie nts wit h s y m pt o matic E G a n d/ or E o D will be ra n d o mize d 
1: 1 t o recei ve 1 of 2 d ose 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  
 
A K 0 0 2 at 1 m g/ k g f or t he first d ose f oll o we d b y 3 m g/ k g a d mi nistere d e ver y 
4  wee ks f or 5 s u bse q ue nt d oses.  
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. 
A p pr o xi matel y  9 0 patie nts wit h E G ± E o D will be e nr olle d, a n d a p pr o xi matel y 
7 0  patie nts wit h E o D wit h o ut E G will be e nr olle d.  
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 efficac y a n d safet y of A K 0 0 2 i n patie nts wit h E G a n d/ or 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. 
Patie 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 t he last d ose 
u nless patie nts elect t o e nter t he o pti o nal l o n g -ter m e xte nsi o n st u d y 
( A K 0 0 2-0 1 6 X).  
Patie nts will be c o nse nte d a n d t he n scree ne d f or u p t o 4 5 da ys pri or t o Da y 1. 
Patie nts w h o meet all eli gi bilit y criteria ca n be e nr olle d i nt o t he st u d y. Patie nts 
w h o d o n ot meet all eli gi bilit y criteria at scree ni n g, or w h o q ualif y at scree ni n g b ut 
are n ot e nr olle d, ma y be assi g ne d a ne w patie nt i de ntificati o n n u m ber a n d 
rescree ne d o nce. Patie nts rescree ne d wit hi n 3 0 da ys of si g ni n g t he i nitial c o nse nt 
will n ot nee d t o si g n a ne w i nf or me d c o nse nt f or m (I C F) if n o c ha n ges ha ve bee n 
ma de t o t he I C F.  
T he st u d y is desi g ne d as f oll o ws:  
 
A n 1 8 t o 4 5 -da y scr ee ni n g peri o d wit h baseli ne e val uati o ns f or st u d y 
eli gi bilit y, i ncl u di n g acti ve s y m pt o ms of disease ( gat here d b y t he patie nt 
re p orte d o utc o me [ P R O] q uesti o n naire c o m plete d d uri n g scree ni n g) a n d E G D 
wit h bi o ps y.  
C CI


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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 2 0  of 1 2 7  
C o nfi d e nti al  
Sec o n d ar y 
O bjecti ves c o nt.  
 
Pr o p orti o n of treat me nt res p o n ders at Wee k 2 4. 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 ≤4 cells/ h pf i n 
5  hi g hest gastric h pf a n d/ or 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 k s 2 3– 2 4.  
 
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 ge fr o m Baseli ne i n 
 o ver ti me. 
 
F or patie nts wit h 
 
): Pr o p orti o n of patie nts 
ac hie vi n g a 
 at 
Wee k 2 4.  
 
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 d ult male a n d fe male patie nts wit h m o derate t o se vere E G a n d/ or E o D 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 Selecti o n 
Criteri a  
I ncl usi o n Criteri a 
Patie 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:  
1)  
Pr o vi de writte n i nf or me d c o nse nt.  
2)  
Male or fe male a ge d ≥1 8 a n d ≤8 0 years at t he ti me of si g ni n g t he i nf or me d 
c o nse nt f or e ntr y.  
3)  
Baseli ne e n d osc o pic bi o ps y wit h ≥3 0 e osi n o p hils/ h pf i n 5 h pf i n t he st o mac h 
a n d/ or ≥3 0 e osi n o p hils/ h pf i n 3 h pf i n t he d u o de n u m, as deter mi ne d b y 
ce ntral hist ol o g y assess me nt of bi o psies c ollecte d d uri n g t he scree ni n g E G D, 
wit h o ut a n y ot her si g nifica nt ca use f or t he e osi n o p hilia.  
 
Pri or E G D ma y be use d f or eli gi bilit y as l o n g as t he E G D occ urre d wit hi n 
3 0  da ys of t he first scree ni n g visit f or t he A K 0 0 2 -0 1 6 st u d y a n d was 
perf or me d a n d ce ntrall y assesse d as f or t he A K 0 0 2 -0 1 6 st u d y.  
4)  
C o m pleti o n of at least 4 dail y P R O q uesti o n naires per we e k f or a mi ni m u m of 
3 wee ks d uri n g scree ni n g.  
 
C CI
C CI
C CI
C CI
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 21 of 127 
Confidential 
Patient Selection 
Criteria cont. 
Inclusion Criteria cont. 
5) 
A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the 
PRO questionnaire (score from 0–10) 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 EG/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. 
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, 
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, or abstain from sexual activity from screening until 
the end of the study, or for 120 days following the last dose of study drug, 
whichever is longer. 
 
Male patients with female partners of childbearing potential must agree to use 
a highly effective method of contraception from screening until the end of the 
study or for 120 days following the 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) 
Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, 
or diet therapy within 4 weeks prior to the screening visit. 
3) 
Treatment with any immunosuppressive or immunomodulatory drugs that 
may interfere with the study within 12 weeks prior to the screening visit. 
4) 
Prior exposure to AK002 or known hypersensitivity to any constituent of the 
study drug. 
5) 
Active Helicobacter pylori infection, unless treated and confirmed to be 
negative prior to randomization and histology per repeat EGD and symptoms 
still qualify for enrollment after treatment.  


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 22 of 127 
Confidential 
Patient Selection 
Criteria cont. 
Exclusion Criteria cont. 
6) 
History of inflammatory bowel disease, celiac disease, achalasia, or 
esophageal surgery. 
7) 
History of bleeding disorders and/or esophageal varices considered to be 
clinically significant by the Investigator. 
8) 
Other significant causes of gastric and/or duodenal eosinophilia or 
eosinophilic granulomatosis with polyangiitis (EGPA). 
9) 
Confirmed diagnosis of hypereosinophilic syndrome (HES). 
10) Women who are pregnant, breastfeeding, or planning to become pregnant 
while participating in the study. 
11) Presence of an abnormal laboratory value considered to be clinically 
significant by the Investigator. 
12) Any disease, condition (medical or surgical), or cardiac abnormality, which, 
in the opinion of the Investigator, would place the patient at increased risk. 
13) 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. 
14) Treatment for a clinically significant helminthic parasitic infection within 
6 months of screening. 
15) Positive helminthic infection on Ova and Parasite (O&P) test.  
16) Seropositive for Strongyloides stercoralis at screening, except for patients 
with past but resolved infection. 
17) Seropositive for HIV or hepatitis at screening, except for vaccinated patients 
or patients with past but resolved hepatitis, at screening. 
18) 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. All types and 
formulations of vaccines (including live attenuated vaccines) authorized by 
FDA or other regulatory authority for the prevention of COVID-19 may be 
administered before, during, or after this 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. 
19) 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 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 2 3  of 1 2 7  
C o nfi d e nti al  
P atie nt Selecti o n 
Criteri a c o nt.  
E xcl usi o n Criteri a c o nt.  
2 0)  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 1)  A n y ot her reas o n t hat i n t he o pi ni o n of t he I n vesti gat or or t he Me dical 
M o nit or ma kes t he patie nt u ns uita ble f or e nr oll me nt.  
Test P r o d uct,  
D ose, a n d 
A d mi nistr ati o n  
A K 0 0 2 ( 
) a n d place b o are s u p plie d as sterile li q ui ds a n d will be dil ute d 
wit h 0. 9 % Na Cl f or i ntra ve n o us (I V) i njecti o n. T he i njecti o n will be a d mi nistere d 
b y I V i nf usi o n, 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 nj ecti o n 
( W FI). 
A K 0 0 2 at a d ose of 1  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 a d mi nistere 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).  
Pri or t o t he first i nf usi o n of A K 0 0 2 or place b o , patie nts will self -a d mi nister 6 0 m g 
oral pre d nis o ne 1 2 – 2 4 h o urs bef ore  t he pre dicte d start of i nf usi o n. 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 writte n a p pr o val of t he Me dical M o nit or.  
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 sec o n d 
i nf usi o n s h o ul d be gi ve n o ver at least a 3-h o ur peri o d. T he t hir d a n d all 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 2-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.  
A n y c ha n ges i n t he i nf usi o n rate sc he d ule d ue t o t olera bilit y will n ot be c o nsi dere d 
de viati o ns fr o m t he pr ot oc ol, as l o n g as t he ma xi m u m i nf usi o n s pee d is n ot 
e xcee de d or i ncrease d be y o n d t he pr ot oc ol s pecifie d li mits.  
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 ur ati o n of 
S u bject 
P artici p ati o n  
T he t otal st u d y d urati o n f or eac h patie nt will be a p pr o xi matel y 8 m o nt hs. T his 
i ncl u des: 
 
A scree ni n g peri o d of  1 8 – 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 da ys ( 3) f oll o wi n g  t he last d ose of st u d y dr u g. 
 
Patie nts w h o e nr oll i n t he A K 0 0 2 -0 1 6 X e xte nsi o n st u d y will partici pate i n t he 
A K 0 0 2 -0 1 6 st u d y 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.  
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 2 4  of 1 2 7  
C o nfi d e nti al  
D ur ati o n of 
S u bject 
P artici p ati o n  c o nt. 
 
Patie nts w h o e nr oll i n A K 0 0 2 -0 1 6 X pri or t o Da y 1 9 7 will n ot c o m plete t he 
Da y 1 9 7 or Da y 2 2 5 pr oce d ures u n der Pr ot oc ol A K 0 0 2 -0 1 6.  
 
Patie nts w h o  e nr oll i n A K 0 0 2 -0 1 6 X after Da y 1 9 7 b ut pri or t o Da y 2 2 5 will 
n ot c o m plete t he Da y 2 2 5 pr oce d ures u n der Pr ot oc ol A K 0 0 2 -0 1 6.  
S af et y E v al u ati o ns  Safet y a n d t olera bilit y will be assesse d t hr o u g h o ut t he st u d y b y m o nit ori n g a n d 
e val uati n g A 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 V 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 i n A K 0 0 2 -0 1 6 
t hr o u g h t he start of st u d y dr u g a d mi nistrati o n i n A K 0 0 2-0 1 6 X if e nr olli n g i n t he 
A K 0 0 2 -0 1 6 X e xte nsi o n st u d y, Da y 2 2 5 if n ot e n r olli n g i n t he A K 0 0 2-0 1 6 X st u d y, 
or Earl y Ter mi nati o n ( E T).  
Se verit y will be assesse d usi n g t he Nati o nal Ca ncer I nstit ute ( N CI) C o m m o n 
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 gra de a n d will be assesse 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 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 ysica l e xa ms ( P E), a n d vital si g ns meas ure me nts. 
T he Me dical M o nit or will re vie w bli n de d safet y data t hr o u g h o ut t he st u d y. Certai 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  
 
) 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 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 n it 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 will be use d t o e val uate si g ns a n d 
s y m pt o ms ass ociate d wit h E G a n d/ or E o D. Patie 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 G/ E o D (a b d o mi nal pai n, na usea, 
a b d o mi nal cra m pi n g, l oss of a p petite, f ull ness bef ore fi n is 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. 
Bi o psies of gastric a n d d u o de nal m uc osa c ollecte d d uri n g pre -treat me nt a n d 
p ost -treat me nt E G D will be e val uate d f or n u m ber of e osi n o p hils. I n a d diti o n, t he 
 will be e val uate d i n patie nts wit h 
. T he 
 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 u si o n. 
 
C CI
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 2 5  of 1 2 7  
C o nfi d e nti al  
Effic ac y a n d 
P h ar m ac o d y n a mic 
E v al u ati o ns c o nt.  
F or patie nts wit h c o nc o mita nt aller gic ast h ma or at o pic der matitis, e val uati o n will 
i ncl u de a q uesti o n f or eac h a b o ut t he se verit y of s y m pt o ms o ver t he past 2 4 h o urs. 
F or all patie nts d uri n g t he scree ni n g peri o d, dail y e val uati o n will i ncl u de a 
q uesti o n a b o ut t he se verit y of d ys p ha gia o ver t he past 2 4 h o urs. After 
ra n d o mizati o n, t his d ys p ha gia q uesti o n will c o nti n ue f or patie nts sc ori n g > 3 o n 
a n y 2 wee ks of scree ni n g d ys p ha gia c o m pleti o n.  
Patie nts will rate t heir q ualit y of life usi n g t he n o n -disease -s pecific 
 at 
vari o us st u d y visits.  
Patie 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 h ar m ac o ki netic 
E v al u ati o ns  
Bl o o d (ser u m) will be c ollecte d f or assess me nt of A K 0 0 2  c o nce ntrati o ns usi n g a 
vali date d e nz y me -li n ke d i m m u n os or be nt assa y ( E LI S A) met h o d.  
P har mac o ki netic ( P K) bl o o d sa m ples will be o btai ne d o n Da ys 1, 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.  
Bl o o d (ser u m) will be c ollecte d f or assess me nt of A K 0 0 2 A D A usi n g a vali date d 
assa y met h o d. A D A bl o o d sa m ples will be o btai ne d pre d ose o n Da ys 1, 2 9, 5 7, 8 5, 
1 1 3, a n d 1 4 1, as well as 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, a n d i n t he e ve nt of a s us pecte d 
i m m u n o ge nicit y-relate d A E .  
S a m ple Size 
C alc ul ati o n  
First C o -P ri m ar y E n d p oi nt:  A s a m ple size of 8 0 patie nts per treat me nt gr o u p 
will ha ve > 9 9 % p o wer t o de m o nstrate a greater pr o p orti o n of res p o n ders at 
Wee k  2 4 i n A K 0 0 2 patie nts w he n c o m pare d t o place b o patie nts, ass u mi n g t he 
pr o p orti o ns of res p o n ders are 0. 6 a n d 0. 1 i n A K 0 0 2 a n d place b o gr o u ps, 
res pecti vel y.  
Sec o n d C o -Pri m ar y E n d p oi nt:  A sa m ple size of 8 0 patie nts per gr o u p will 
pr o vi de 9 6 % p o wer t o detect a statisticall y si g nifica nt differe nce of 7. 4 p oi nts 
bet wee n A K 0 0 2 a n d place b o i n t he mea n re d ucti o n fr o m baseli ne  i n T S S at 
Wee ks  2 3 – 2 4, ass u mi n g a c o m m o n sta n dar d de viati o n of 1 2. 5 p oi nts a n d a 
p o p ulati o n mea n Baseli ne T S S of 3 0 p oi nts ( A K 0 0 2 -0 0 3 data o n file).  
St atistic al A n al ysis  T he pri mar y efficac y a nal ysis p o p ulati o n is  t he M o difie d I nte nt -t o-Treat ( MI T T) 
p o p ulati o n, defi ne d as all ra n d o mize d patie nts w h o ha ve recei ve d at leas t 
1  i nf usi o n of st u d y dr u g. T he sec o n dar y efficac y a nal ysis p o p ulati o n is t he 
Per  Pr ot oc ol ( P P) p o p ulati o n, defi ne d as MI T T patie nts w h o ha ve recei ve d at least 
1  i nf usi o n of st u d y dr u g a n d di d n ot ha ve si g nifica nt pr ot oc ol vi olati o ns p ossi bl y 
i nterferi n g wit h assess me nt of efficac y. T he safet y p o p ulati o n is defi ne d as all 
patie nts w h o are ra n d o mize d a n d ha ve recei ve d at least 1 i nf usi o n of st u d y dr u g.  
 
C CI
C CI
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 26 of 127 
Confidential 
Statistical Analysis 
cont. 
The MITT population 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 EG and/or 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 
comparing AK002 with placebo for the proportion of treatment responders. 
Patients who experience an intercurrent event (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. Additionally, 
the between group difference and the associated 95% CI will be computed and 
presented.  
Sensitivity analysis will be carried out using the Cochran-Mantel-Haenszel (CMH) 
test stratified by the randomization stratification factors (Baseline TSS<28 vs ≥28 
and EG ± EoD [i.e., EG with or without EoD] versus EoD-only).  
The second co-primary endpoint will be analyzed by analysis of covariance 
(ANCOVA). The least square (LS) mean, standard error (SE), and 95% 
Confidence Interval for each treatment group and for the between group difference 
will be derived from ANCOVA with treatment as a factor, Baseline PRO TSS 
(continuous) and EoD without EG (categorical) as covariates. Data on patients 
who experience an intercurrent event (i.e., exit the study prematurely or initiate 
prohibited or restricted medications) prior to the end of Week 24 will be set to 
missing.  
Detailed specifications for the missing data imputation will be provided in the 
Statistical Analysis Plan (SAP).  
Analysis of binary secondary endpoints will be based on the methods outlined 
above for the first co-primary efficacy analysis. 
Change from baseline in continuous secondary outcomes measured at multiple 
post-baseline time points will be analyzed longitudinally using a mixed model. 
The model will include fixed effects for baseline value, treatment, week, and the 
treatment by week interaction and allow for random subject effects and assume an 
unstructured covariance structure. The Kenward-Rogers approach for computing 
denominator degrees of freedom will be used to account appropriately for pooling 
of within and between-subject variance estimates. Least square means and the 
95% CI for the between group difference will be estimated for each week. 


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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 28 of 127 
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 AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 29 of 127 
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- 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 the 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 IV 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 IV administration of AK002 to transgenic 
mice was 100 mg/kg, which supports the Phase 1 studies in humans.  
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, and eosinophilic gastritis (EG) and/or eosinophilic 
duodenitis (EoD), which was previously referred to as eosinophilic gastroenteritis (EGE).  
Multiple doses of 3 mg/kg have been given to patients with ISM, CU, severe AC, mast cell 
gastritis, 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, healthy volunteers and patients with ISM, CU, severe AC, EG/EoD, EoE, and mast cell 
gastritis have been enrolled in clinical studies. In general, AK002 has been well tolerated. The 
most common treatment-emergent adverse event (TEAE) observed was infusion-related reaction 
(IRR). Most IRR were mild to moderate and resolved on their own, with no treatment required. 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 30 of 127 
Confidential 
Infusion-related reactions that were serious resolved within approximately 24 hours. 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, 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, versus a 10% increase for placebo-treated patients (p<0.0001). The 
reduction of eosinophils was associated with a statistically significant reduction in total symptom 
score (TSS) of 58% in the high dose AK002 group and 49% reduction in the low dose AK002 
group versus 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) versus 5% for placebo-treated patients (p<0.0001).  
Approximately 40% of patients had concomitant eosinophilic esophagitis (EoE). In those 
patients, a mean reduction of 95% of eosinophils/hpf in esophageal biopsies for AK002-treated 
patients was observed versus no change for placebo-treated patients. Also, 13 of 14 AK002-
treated patients (93%) were histologic responders as defined by ≤6 eosinophils/hpf versus 1 of 
9 placebo-treated patients (11%). Dysphagia improved by 53% in AK002-treated patients versus 
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 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 31 of 127 
Confidential 
second dose for 20 of the 58 patients dosed. Using this premedication regimen, no IRR were 
observed on the first infusion of the extension study.  
2.4 
Eosinophilic Gastrointestinal Disorders  
Eosinophilic gastrointestinal disorders (EGID) are chronic inflammatory disorders characterized 
by infiltration of eosinophils along different segments of the gastrointestinal (GI) tract, in the 
absence of any cause of the eosinophilia (Caldwell, 2014). 
Eosinophilic gastritis and/or eosinophilic duodenitis (previously referred to as eosinophilic 
gastroenteritis) represent what 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 eosinophilic duodenitis (EoD) is more appropriate. The 
gastrointestinal symptoms are believed to be due to the release of inflammatory mediators from 
activated eosinophils, and likely mast cells. Symptoms that are often severe and 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.  
Patients may also have concomitant atopic diseases like food allergy, asthma, and atopic 
dermatitis, which further impact qualify of life and contribute to health care costs. Additionally, 
8% to 10% of patients have concomitant EoE (Jensen, 2016).  
There are no FDA-approved treatments for EG and/or EoD. Current therapies and disease 
management include dietary restriction/elimination, PPI, antihistamines, systemic or topical 
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 EG 
and/or 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 


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 3 2  of 1 2 7  
C o nfi d e nti al  
a d diti o n, c o m plia nce is ver y p o or, a n d p atie nt q ualit y of life is greatl y i m pacte d ( Be dell, 2 0 1 8 ; 
Peters o n,  2 0 1 3 ; Wec hsler, 2 0 1 4 ). C ortic oster oi ds, s yste mic or t o pical (s wall o we d) ha ve b ee n 
s h o w n t o pr o vi de s y m pt o m relief b ut are n ot a p pr o priate f or l o n g-t er m treat me nt d ue t o 
n u mer o us si de effects a n d ass ociate d ris ks i ncl u di n g a dre nal i ns ufficie nc y, b o ne 
de mi neralizati o n, i ncreas e d c ha n ce of i nfecti o n, oste o p or osis, be ha vi oral iss ues, a n d wei g ht gai n.  
B y mar k e dl y re d uci n g t h e n u m ber of bl o o d a n d tis s 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 b e 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 has e 2 data wit h A K 0 0 2 t hat s h o ws si g nifica nt i m pr o v e me nt i n hist ol o g y 
a n d s y m pt o ms i n t hese  p atie nts.  
Gi ve n t here are n o a p pr o ve d t hera pies f or t hese c hr o nic a n d de bilitati n g dis eases, better 
treat me nt o pti o ns are cle arl y n ee d e d t o ma na ge E G a n d E o D. 
3.  
R ati o n ale f or St u d y a n d D ose Selecti o n  
Base d o n e x perie nce wit h A K 0 0 2 i n healt h y v ol u nteers a n d  i n patie nts wit h I S M, C U, se vere 
A C, a n d E G/ E o D, t he pr o p ose d A K 0 0 2 d ose re gi me n of 6 t otal d oses is 1  m g/ k g f or t he first 
i nf usi o n, f oll o we d b y 5 d oses of 3 m g/ k g a d mi nistere d e v er y 4  wee ks.  
 
 
 
T he i nf usi o ns were ge nerall y w ell t olerate d at all d oses wit h m ost I R R bei n g mil d t o m o derate 
a n d ver y fe w A E  o utsi de t he i nf usi o n wi n d o w. Patie nts wit h I S M, C U, se vere A C, mast cell 
gastritis, a n d E G/ E o D h a ve recei ve d m o nt hl y d os es of 1 m g/ k g a n d 3 m g / k g A K 0 0 2. 
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4.
Study Objectives 
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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 3 4  of 1 2 7  
C o nfi d e nti al  
 
Pr o p orti o n of treat me nt r es p o n ders at Wee k 2 4. 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 ≤4 cells /h pf i n 5 hi g hest gastric h pf a n d/ or 
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 u cti o n i n T S S fr o m B aseli ne t o Wee ks 23 – 2 4.  
 
Pr o p orti o n of patie nts w h o ac hie ve ≥7 0 % re d u cti o n i n T S S fr o m B aseli ne t o Wee ks 23 – 2 4.  
 
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 bjecti ves  
T he e x pl orat or y o bj ecti v es are t o e val uate t he effect of A K 0 0 2 b y c o m p ari n g A K 0 0 2 t o place b o 
treat me nt f or t he f oll o wi n g parameters:  
 
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 . 
 
F or patie nts wit h 
 
: Pr o p orti o n of patie nts ac hie vi n g a 
 
 at W ee k 2 4. 
 
C ha n ge fr o m Baseli ne i n 
 o ver ti me . 
4. 4  
S afet y O bjecti ves  
T o e val uate t he s afet y a n d t olera bilit y of A K 0 0 2 b y det er mi ni n g i nci d e nce a n d se verit y of 
a d verse e ve n ts, st u d y wit h dra wals d ue t o a d verse e ve nts, c ha n ges i n vital si g ns a n d la b orat or y 
tests i ncl u di n g i m m u n o ge nicit y, c ha n ges i n c o n c o mita nt me dicati o n use d ue t o a d verse e ve nts, 
a n d ot her safet y para met ers.  
4. 5  
T ar get of Esti m ati o n  
T he esti ma n d (tar get of esti ma ti o n) f or Pr ot oc ol A K 0 0 2-0 1 6 is : 
 
I n p atie nts wit h E G a n d/ or E o D, w h at is bet wee n gr o u p ( A K 0 0 2 vs. Pl a ce 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 Weeks 2 3– 2 4 as me as ure d by t he  p atie nt -re p orte d 
o utc o me ( P R O) q uesti o n n aire.  
T he s ecti o ns bel o w des cri be t he attri b utes of t he esti ma n d c o nsiste nt wit h t he I C H E 9 A d de n d u m  
(F D A, 2 0 2 1 ). 
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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 3 9  of 1 2 7  
C o nfi d e nti al  
T a ble 1  
Sc he d ule of Assess me nts  
 
Scree ni n g  
( 1 8– 4 5 da ys)  
Tre at me 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  
 
 
D a y 8  
( ± 2 da ys) 
 
D a y 1 5  
( ± 2 da ys)  
 
D ose 2  
D a y 2 9  
( ± 3 da ys) 
D ose 3  
D a y 5 7  
( ± 3 da ys) 
D ose 4  
D a y 8 5  
( ± 3 da ys) 
D ose 5  
D a y 1 1 3  
( ± 3 da ys) 
D ose 6  
D a y 1 4 1  
( ± 3 da ys) 
D a y 1 6 9  
( ± 3 da ys) or 
2 8 da ys 
after last 
d ose  
D a y 1 7 6  
( ± 3 da ys) or 
3 5 da ys 
after last 
d ose if E T 2 9 
D a y 1 9 7  
( ± 3 da ys) or 
5 6  da ys 
after last 
d ose if E T 2 9 
D a y 2 2 5  
( ± 3 da ys) or 
8 4  da ys 
after last 
d ose if E T 2 9 
I nf or me d c o nse nt 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gr a p hics  
X  
 
X  
 
 
 
 
 
 
 
 
 
 
 
Me dical Hist or y  
X  
 
X  
 
 
 
 
 
 
 
 
 
 
 
Pri or/ C o nc o mita nt Me dicati o ns  
X  
 
X  
 
 
X  
X  
X  
X  
X  
X  
X  
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  
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  
Baseli n e Diet Assess me nt 7 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseli n e Diet C o m plia nce 8 
 
 
X  
 
 
X  
X  
X  
X  
X  
 
X  
X  
X  
St o ol f or O va a n d Parasite 9 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
e P R O Acti vati o n a n d Trai ni n g 1 0 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
e P R O Q u esti o n naire ( ma y 
i ncl u de A d diti o nal Q u esti o ns)1 1 
< ------------------------------------------------------------------C o m plete electr o nicall y o ne ti me d ail 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, a n d St u d y Da y 2 8 ---------------------------------------->  
 
< ---------------------------------------------------C o m plete electr o nicall y o n  St u d y Da y 7 a n d St u d y Da y 2 8 ----------------------------------------------------->  
E G D wit h Bi o ps y 1 2, 1 4 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
Bl o o d f or Scree ni n g C he mistr y 
(i ncl u des h C G a n d F S H)1 2, 1 5 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI
C CI
C CI


Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 40 of 127 
Confidential 
Table 1 
Schedule of Assessments cont. 
 
Screening 
(18–45 days) 
Treatment Period 
(20 weeks) 
Follow-Up Period30 
(12 weeks) 
Baseline1 
Prior 
to 
Day 1 
Dose 1 
Day 1 
 
 
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 
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 ET29 
Blood for Serology and 
Strongyloides stercoralis 12,16 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for Total Serum IgE12,17 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Previous Treatments Review 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Access IRT: Stratification and 
Randomization18 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Access IRT: IP Kit Assignment 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Premedication: Prednisone19 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration20 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Blood for CBC with 
differential12,21 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Chemistry12,22 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for PK12,23 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for ADA12,24 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine for Urinalysis12,25 
X 
 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Dipstick Pregnancy Test26 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Non-serious Adverse Events27 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events28 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Begin AK002-016X extension 
study at least 1 day after 
Day 176 Visit (if applicable)31 
 
 
 
 
 
 
 
 
 
 
 
X33 
X33 
X33 
Blood for histamine/tryptase32 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 


Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 4 1  of 1 2 7  
C o nfi d e nti al  
T a ble 1 N otes  
A D A:  A nti -A K 0 0 2 a nti b o d y  
E T:  
Earl y T er mi nati o n  
I R T: 
I nteracti ve Res p o nse T ec h n ol o g y 
C B C:  C o m plete bl o o d c o u nt  
F S H:  F ollicle -sti m ulati n g h or m o ne 
  
E C G:  Electr ocar di o gra m  
h C G:  H u ma n C h ori o nic G o na d otr o pi n  
 
 
e P R O: electr o nic P at ie nt Re p orte d O utc o me 
I P: 
I n vesti gati o nal Pr o d uct 
P K:  
P har mac o ki netics  
1)  
Baseli ne scree ni n g visit ca n o cc ur o ver se veral da ys wit hi n t he scree ni n g peri o d. Da y 1 ca n be gi n as s o o n as eli gi bilit y crit eria are met  a n d at least 4 diar y e ntries ha ve bee n 
c o m p lete d d uri n g t he t hir d we e k of scree ni n g.  
2)  
At scree ni n g, hei g ht (i n c m) a n d wei g ht (i n k g) will be rec or de d. B o d y wei g ht will als o be meas ure d o n 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 1 7 6 , Da y 1 9 7  a n d 
Da y 2 2 5  or 2 8 , 5 6 , a n d 8 4 da ys after las t 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 calc ulate t he a m o u nt of A K 0 0 2/ place 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 eac h i nf usi o n da y.  
3)  
Vital si g ns will be meas ure d at scree ni n g, D a 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 last d ose if E T a n d o n all d osi n g da ys: wit hi n 3 0 mi n utes pre d ose, 1 5 mi n utes 
( ± 5 mi n utes) after t he start of st u d y dr u g i nf usi o n, wit hi n 1 5 mi n utes 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 g e. A d diti o nal vital si g ns meas ure me nts ma y be 
c ollecte d at t he I n vesti gat or’s discreti o n if a n I R R occ urs. Vital si g ns i ncl u di n g s yst olic a n d diast olic bl o o d press ure, p ul se, b o d y te m perat ure, a n d res pirat or y rate will be 
meas ure d after t he patie nt has bee n at rest f or ≥5 mi n utes a n d bef ore a n y bl o o d dra ws ha ve bee n o btai ne d ( u nless c ollect e d f or a n I R R).  
4)  
A 1 0 -lea d or 1 2-lea d E C G will b e o btai ne d at scree ni n g bef ore a n y bl o o d is dra w n a n d after t he patie nt has bee n i n t he a p pr o priate p ositi o n for ≥5 mi n u tes. 
5)  
A c o m plete p h ysical e xa mi nati o n will be perf or me d b y eit her t he I n vesti gat or or desi g nee a n d i ncl u de t he f oll o wi n g b o d y s yste m or or ga n assess me nts: s ki n; hea d, e yes, ears, 
n ose a n d t hr oat; t h yr oi d; l u n gs; car di o vasc ular; a b d o me n; e xtre mities; l y m p h n o des; a n d a brief ne ur ol o gical e xa mi nati o n.  
6)  
A s y m pt o m -directe d P E (i ncl u di n g assess me nt of p ossi ble i nf usi o n site reacti o ns) will be perf or me d b y t he I n vesti gat or or desi g nee, as nee de d if a n y s y m pt o ms are re p orte d.  
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 dize d q uesti o ns. Eati n g patter ns, f o o d a v oi da nce be ha vi ors, a n d c o nfir me d all er gies will be ca pt ure d.  
8)  
A baseli ne diet c o m plia nce c h ec k will be perf or me d at e ver y st u d y visit, e xce pt as  n ote d a b o ve, a n d a n y varia nces fr o m t he baseli ne diet d oc u me nte d. P atie nts s h o ul d 
mai ntai n t he baseli ne diet t hr o u g h o ut t he st u d y.  
9)  
Fecal c ollecti o n kits f or O va a n d P arasite test will be pr o vi de d t o patie nts at scree ni n g. C ollecti o n kits s h o ul d be ret u r ne d t o t he cli nical site wit hi n 1 da y of c ollecti o n. 
Ne gati ve res ults m ust b e a vail a ble pri or t o ra n d o mizati 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 me a n d pass w or d. P R O q uesti o n naire s h o ul d be acti vate d f or a ll patie nts o n scree ni n g Da y 1. P atie nts wit h 
c o nc o mita nt hist or y of ast h ma or at o pic der matitis will recei ve a n e xtra q uesti o n, a b o ut eac h, as a p pr o priate. All patie nts w ill recei ve d ys p ha gia q uesti o n d uri n g scree ni n g a n d 
will c o nti n ue t o recei ve t he q uesti o n after e nr oll me nt if wee kl y a vera ge d ys p ha gia is ≥3 d uri n g a n y 2 wee ks of scree ni n g.  
1 1)  P R O s h o ul d be c o m plete d ar o u n d t he sa me ti me eac h da y. Pri or t o e nr oll me nt, t he P R O wee kl y a vera ges of a b d o mi nal pai n, na usea , a n d diarr hea o ver t he scree ni n g peri o d 
will b e ca lc ulate d a n d use d t o assess eli gi bilit y. Wee kl y a ver a ge T otal S y m pt o m Sc ore ( T S S 6) will be calc ulate d f or eli gi bilit y a n d stratificati o n. P R O wee kl y a vera ge f or 
d ys p ha gia will als o be assesse d pri or t o e nr oll me nt t o deter mi ne if t he patie nt s h o ul d c o nti n ue  recei vi n g t he 1-q uesti o n dail y d ys p ha gia q uesti o n.  
1 2)  S peci me n pr ocesse d b y ce ntral la b orat or y. See ce ntral la b orat or y ma n ual f or c ollecti o n a n d pr ocessi n g details.  
C CI
C CI


Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 42 of 127 
Confidential 
Table 1 Notes cont. 
13) To be completed electronically by patient, in clinic, prior to any blood draw, physical exam, or vital sign measurements. 
14) See Appendix 5 for biopsy assessments. The post-treatment endoscopy (EGD) and biopsy assessments will be performed on Day 169 (±3) or 28 (±3) days after last dose of 
study drug if ET. If the Day 141 infusion occurs out of window, the EGD should occur 28 (±3) days from the date of Day 141. Post-treatment EGD 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 and whether patient is EoD-only will occur. Randomization and stratification will be conducted through the IRT system. 
19) Premedication with 60 mg oral prednisone or approved alternative is required 12–24 hours prior to first infusion. Premedication may be administered prior to subsequent 
infusions at the Investigator’s discretion, but only with written Medical Monitor approval. 
20) Study drug will be administered as a single peripheral IV infusion over at least 4 hours for Dose 1 and at least 3 hours for Dose 2. Doses 3–6 should occur over at least 
2 hours, depending on prior infusion tolerability. Please refer to the Pharmacy Manual. 
21) Blood for CBC with differential, including absolute blood eosinophil count, will be obtained just prior to each infusion, 1 hour (±15 minutes) after the end of each infusion as 
well as during the screening period, and on Days (±3) 8, 15, 169, 176, 197, and 225 or 35, 56, and 84 (±3) days after last dose if ET. All differential blood counts from Day 1 
(post-dose) 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 predose on dosing Days 1, 29, 57, 85, 113, and 141, as well as on 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. 
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 (±3), 35 (±3), 
56 (±3), and 84 (±3) days after last dose of study drug if ET. 
24) Blood for ADA will be collected 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 (±3), 35 (±3), 
56 (±3), and 84 (±3) days after last dose of study drug if ET. ADA sample will also be collected any time an immunogenicity-related AE occurs. 
25) Urine for standard urinalysis will be obtained predose on dosing Days 1, 29, 57, 85, 113, and 141 as well as during the screening period and on Day 176 and Day 197 or 
35 (±3) days and 56 (±3) days after last dose of study drug if ET. 
26) A small amount of urine collected for urinalysis will be used for dipstick pregnancy test on all infusion days and on Day 176 and 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 adverse events of special interest will begin after the first dose of study drug has occurred. 


Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 43 of 127 
Confidential 
Table 1 Notes cont. 
28) The reporting of SAE occurring after signing 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. 
29) Patients who sign the informed consent for the AK002-016X extension study will complete the procedures for Day 176 and may begin open-label dosing in the extension 
study, if eligible, one day after the completion of Day 176 visit. In this case, patients will not complete the Day 197 or Day 225 procedures under Protocol AK002-016. 
Open-label dosing and follow-up will occur under the AK002-016X extension study. Patients who choose to enter the AK002-016X extension study after Day 197 but before 
Day 225 will not complete Day 225 procedures.  
30) The ET visits should be conducted 28 (±3), 35 (±3), 56 (±3), and 84 (±3) days after the 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 and end-of-study blood work may occur on the same day (28 days after last dose and 35 days after last dose visit procedures). If the 
end-of-study visit occurs more than 35 days after the 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. 
31) The final hematology assessment for AK002-016 must be collected prior to the subject taking prednisone premedication for AK002-016X. Therefore, dosing in 
AK002-016X must take place at least 1 day after completion of the Day 176 visit for AK002-016. Subjects may start AK002-016X dosing 1 day after completion of the 
Day 176 Visit. 
32)  Blood samples for histamine and tryptase to be collected within 1–2 hours of start of symptoms if there is any suspicion of anaphylaxis. 
33)  For patients who do not start the extension study before Day 197 or Day 225, visit procedures will occur according to the AK002-016 study. 
 
 


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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 4 6  of 1 2 7  
C o nfi d e nti al  
 
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 . 
 
F or patie nts wit h 
 
): Pr o p orti o n of patie nts ac hie vi n g  a 
 
 at W ee k 2 4. 
 
C ha n ge fr o m Baseli ne i n 
 o ver ti me . 
7.  
P ati e nt Selecti o n  
7. 1  
N u m ber of P atie nts  
A t otal of a p pr o xi matel y 1 6 0 patie nts will be d ose d i n t he st u d y i n w hic h 8 0 patie nts will recei ve 
A K 0 0 2 at a d ose  of 1  m g/ k g f or t h e first d ose f oll o we d b y 3  m g/ k g f or 5 s u bse q ue nt d oses a n d 
8 0  patie nts will recei ve place b o, i n a ra n d o mize d, d o u ble -bli n d ma n ner. T h e st u d y will ai m t o 
e nr oll a p pr o xi matel y 9 0 patie nts wit h E G  ± E o D a n d a p pr o xi matel y 7 0  patie nts  wit h E o D o nl y.  
7. 2  
St u d y P o p ul ati o n  
Male a n d fe male E G a n d/ or E o D patie nts, a ge d ≥1 8 a n d ≤8 0 years w h o f ulfill t he eli gi bilit y 
criteria s pecifie d bel o w.  
7. 3  
I ncl usi o n Criteri a 
Patie nts wit h E G a n d/ or E o D are eli gi ble f or e nr oll me nt i nt o t he st u d y if all of t he f oll o wi n g 
criteria are met:  
1)  
Pr o vi de writte n i nf or me d c o nse nt.  
2)  
Male or fe m ale a ge d ≥1 8 a n d ≤8 0 years at t he ti me of si g ni n g t he i nf or me d c o nse nt f or 
e ntr y.  
3)  
Baseli ne e n d osc o pic bi o ps y wit h > 3 0 e osi n o p hils/ h pf i n 5 h pf i n t he st o mac h a n d/ or 
> 3 0  e osi n o p hils/ h pf i n 3 h pf i n t he d u o de n u m, as deter mi ne d b y ce ntral hist ol o g y 
assess me nt of bi o psies c ollecte d d uri n g t he scree ni n g E G D, wit h o ut a n y si g nifica nt ca use 
f or t he e osi n o p hilia.  
 
Pri or E G D ma y be use d f or eli gi bilit y as l o n g as t he E G D occ urre d wit hi n 3 0 da y s of t he 
first scree ni n g visit f or t h e A K 0 0 2-0 1 6 st u d y a n d was perf or me d a n d ce ntr all y ass esse d as 
f or t he A K 0 0 2-0 1 6 st u d y.  
4)  
C o m pleti o n of at least 4 dail y P R O q uesti o n naires per wee k f or a mi ni m u m of 3 wee ks 
d uri n g scree ni n g.  
C CI
C CI
C CI
C CI
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 47 of 127 
Confidential 
5) 
A weekly average score of abdominal pain, nausea, and/or diarrhea ≥3 on the PRO 
questionnaire (score from 0–10) 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 EG/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. 
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, 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, or abstain from sexual 
activity from screening until the end of the study, or for 120 days following the last dose of 
study drug, whichever is longer. 
 
Male patients with female partners of childbearing potential must agree to use a highly 
effective method of contraception from screening until the end of the study or for 120 days 
following the 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 late menstrual 
period) at any time during study participation. 
7.4 
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) 
Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet 
therapy within 4 weeks prior to screening. 
3) 
Treatment with any immunosuppressive or immunomodulatory drugs that may interfere 
with the study within 12 weeks prior to the screening visit. 
4) 
Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug. 
5) 
Active Helicobacter pylori infection, unless treated and confirmed to be negative prior to 
randomization and histology per repeat EGD and symptoms still qualify for enrollment 
after treatment. 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 48 of 127 
Confidential 
6) 
Confirmed history of inflammatory bowel disease, celiac disease, achalasia, or esophageal 
surgery. 
7) 
History of bleeding disorders and/or esophageal varices considered to be clinically 
significant by the Investigator. 
8) 
Other significant causes of gastric and/or duodenal eosinophilia or eosinophilic 
granulomatosis with polyangiitis (EGPA). 
9) 
Confirmed diagnosis of Hypereosinophilic Syndrome (HES). 
10) Women who are pregnant, breastfeeding, or planning to become pregnant while 
participating in the study. 
11) Presence of an abnormal laboratory value considered to be clinically significant by the 
Investigator. 
12) Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion 
of the Investigator, would place the patient at increased risk. 
13) 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. 
14) Treatment for a clinically significant helminthic parasitic infection within 6 months of 
screening. 
15) Positive helminthic infection on Ova and Parasite (O&P) test. 
16) Seropositive for Strongyloides stercoralis at screening, except for patients with past but 
resolved disease. 
17) Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients 
with past but resolved disease. 
18) 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. All types and formulations of vaccines (including 
live attenuated vaccines) authorized by FDA or other regulatory authority for the prevention 
of COVID-19 may be administered before, during, or after this 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. 


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 4 9  of 1 2 7  
C o nfi d e nti al  
1 9)  Partici pati o n i n a c o nc urre nt i nter ve nti o nal st u d y wit h t he last i nter ve nti o n occ urri n g wit hi n 
3 0 da ys pri or t o s t u d y dr u g a d mi nistrati o n or 9 0 d a ys or 5 half-li ves, w hic h e ver is l o n ger, 
f or bi ol o gic pr o d ucts. 
2 0)  K n o w n hist or y of alc o h ol, dr u g, or ot h er s u bsta nce a b use or de pe n d e nce t h at 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 1)  A n y ot her reas o n t hat i n t he o pi ni o n of t he I n vesti gat or or t he Me dical M o nit or ma kes t he 
patie nt u ns uita ble f or e nr oll me nt.  
7. 5  
S afet y E v al u ati o ns  
Safet y a n d t olera bilit y will be assesse d t hr o u g h o ut t he st u d y b y m o nit ori n g a n d e val uati n g A E  
i ncl u di n g a n y c o mplicati o ns res ulti n g fr o m t he I V 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 i n A K 0 0 2-0 1 6 t hr o u g h t h e start of st u d y dr u g a d mi nistrati o n i n 
A K 0 0 2 -0 1 6 X (Da y 1 7 6 if e nr olli n g i n t he A K 0 0 2 -0 1 6 X e xte nsi o n st u d y ), Da y 2 2 5 if n ot 
e nr olli n g i n t he A K 0 0 2 -0 1 6 X st u d y, or E arl y Ter mi nati o n ( E T) . 
Se verit y will be assesse d usi n g t he Nati o nal Ca ncer I nstit ute ( N CI) C o m m o n Ter mi n ol o g y 
Criteria f or A d v erse E v e nts ( C T C A E) 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 v erit y gra de a n d will be assesse 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 diti o nal safet y e val u ati o ns i ncl u de cli nical la b orat or y tests c o m prisi n g A D A t o A K 0 0 2, C B C, 
c he mistries a n d uri nal yses, p h ysical e x a ms, a n d  vital si g ns meas ure me nts.  
T he Me dical M o nit or will re vie w bli n de d safet y d ata t hr o u g h o ut t he st u d y. Certai n safet y d ata 
( p ost-treat me nt c ell differe 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 h e desi g nate d S afet y M o nit or 
will re vie w bli n de d safet y dat a as well as p ost -tr eat 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 h at d oes n ot ca use bias.  
A n i n de pe n de nt D ata M o nit ori n g C o m mi ttee (i D M C) has bee n c o n v e ne d a n d will meet at 
re g ularl y sc h e d ule d i nter vals i n acc or da nce wit h t he i D M C c harter.  
8.  
Pri or a n d C o nc urre nt Me dic ati o ns  
Pri or a n d c o nc o mita nt m e dicati o ns i ncl u de b ot h prescri be d a n d o ver -t he-c o u nter me dicati o ns a n d 
will be rec or d e d i n t he el ectr o nic Case R e p ort F or ms (e C R F) f or 3 0 d a 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 G a n d/ or E o D s y m pt o ms, e ve n if t he y are 
> 3 0  da ys bef ore t he s cree ni n g visit will be d oc u me nte d i n t he e C R F.  
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 50 of 127 
Confidential 
Any medication must 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. 
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 during the conduct of EGD must also be documented.  
8.1 
Prohibited Medications  
Any biologics or other medications that may interfere with the study, such as 
immunosuppressive or immunomodulatory drugs (i.e., azathioprine, JAK inhibitors, 6-
mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-5, anti-IL-5 receptor, 
dupilumab, anti-IgE antibodies, omalizumab) are prohibited medications. The use of systemic or 
topical corticosteroids with a dose of >10 mg/day of prednisone or equivalent is prohibited 
unless it is due to unforeseen circumstances when it is deemed to be medically necessary to treat 
an unrelated medical condition or when given as a premedication prior to infusion or to treat an 
IRR that occurs during infusion. 
If a prohibited medication other than corticosteroids as described above 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.  
8.2 
Allowed Medications  
Medications, other than those that are prohibited (Section 8.1) such as antihistamines, 
leukotriene antagonists, and sodium cromolyn, are allowed during the study and, unless required 
due to unforeseen medical necessity, doses are to remain stable. All medication use during the 
screening period and throughout the study will be documented in the CRF. Any medications 
used for the treatment of IRR are not considered deviations from the protocol.  
Systemic or swallowed corticosteroids with a dose of ≤10 mg/day of prednisone or equivalent 
are acceptable, as long as the dose remains stable throughout screening and during the study.  
The use of systemic or topical corticosteroids with a dose of >10 mg/day of prednisone or 
equivalent is permitted if it is deemed to be medically necessary to treat an unrelated medical 
condition or when given as a premedication prior to infusion or to treat an IRR that occurs during 
infusion. 


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 5 1  of 1 2 7  
C o nfi d e nti al  
9.  
St u d y Tre at me nt  
9. 1  
F or m ul ati o n of Test Pr o d uct a n d Pl ace b o  
A K 0 0 2 is a h u ma nize d n o n -f uc os ylate d I g G 1 m o n ocl o nal a nti b o d y dir ecte d a gai nst Si glec-8. 
A K 0 0 2 dr u g pr o d uct is s u p plie d as a sterile li q ui d i n a si n gle -us e 1 0 R gl ass vial wit h a fill 
v ol u me of n ot less t ha n 1 0 m L. T he pr o d uct is st ore d at 2° C t o 8° C. T he A K 0 0 2 f or m ulati o n is 
 
 p H 6. 0, i n steril e Water f or I njecti o n.  
P lace b o is s u p plie d as a sterile li q ui d i n a si n gle-us e 1 0 R glass vial wit h a fill v ol u me of 
a p pr o xi matel y 1 0. 6 m L. Place b o c o ntai ns 
 
, p H 6. 0, i n sterile Water for I njecti o n.  
N ote : A K 0 0 2 a n d place b o will be referre d t o as “st u d y dr u g. ”  
9. 2  
St u d y Dr u g P ac k a gi n g a n d L a beli n g  
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 gl e -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 are pl u g ge d wit h Tefl o n -c oat e d r u b ber st o p pers a n d seale d 
wit h al u mi n u m seals.  
Eac h vial will be la bel e d wit h t he re q uire d i n vesti gati o nal use st ate me nt, l ot n u m ber, kit n u m ber, 
S p o ns or na me, a n d directi o ns f or st ora ge. 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 os e 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 re q uire d re g ulat or y d o c u me ntati o n a n d a p pr o vals ha ve b ee n 
recei v e d b y t he S p o ns or, c o ntract has b ee n e x ec ute d, a n d t he first scree n e d patie nt is e ntere d i nt o 
t he I R T. S u bse q u e nt st u d y dr u g s hi p me nts will be tri g gere d a ut o maticall y b ase d o n 
pre deter mi ne d s u p pl y le v els a n d e nr oll me nt acti vit y at t he site.  
9. 4  
St u d y Dr u g D os a ge/ D os a ge Re gi me n  
Patie nts will be ra n d o ml y assi g ne d t hr o u g h t he I R T s yste m t o a n acti ve d ose gr o u p of 1 m g/ k g 
A K 0 0 2 f oll o we d b y 5 d oses of 3 m g/ k g or pl ace b o. T he e x act d ose will be calc ulate d pri or t o 
eac h i nf usi o n a n d b ase d o n c urre nt p atie 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 V i nf usi o n usi n g a n i nf usi o n p u m p as i n dicate d i n t he st u d y P har mac y Ma n u al o n 
Da ys 1, 2 9 ( ± 3), 5 7 ( ± 3), 8 5 ( ± 3), 1 1 3 ( ± 3), a n d 1 4 1 ( ± 3).  
C CI
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 52 of 127 
Confidential 
9.5 
Preparation of Study Drug 
A study pharmacist or designee will prepare the study drug for each infusion. Based on patient 
weight obtained the day of dosing, the designated study pharmacist will prepare the appropriate 
dilution of AK002 or placebo for IV administration.  
Appropriate aseptic technique will be used, and the drug will be prepared according to the 
pharmacy manual for AK002. Please refer to the Pharmacy Manual for additional details and 
step-by-step instructions regarding study drug preparation. 
Based on current USP 2019 guidelines, 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 the 
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 3 hours on Study Day 29 (±3), and over at least 2 hours on Study 
Days 57 (±3), 85 (±3), 113 (±3), 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 60 mg oral prednisone (or 
approved equivalent) 12–24 hours prior to the start of the study drug infusion. For subsequent 
infusions, premedication may be used at the discretion of the Investigator and with written 
approval from the Medical Monitor.  
The IV 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 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 53 of 127 
Confidential 
completed within 8 hours of preparation. Administration will also be discontinued in any patient 
experiencing a SAE during the course of the infusion.  
The patient will be observed for at least 1 hour after the end of each infusion, as per Investigator 
discretion.  
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 NaCl 0.9% 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 reported to the Sponsor or 
designee and captured as a deviation. The Sponsor will notify the site if the study drug is to be 
quarantined or if it can be used. 
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 is an active kit or 
a placebo kit. 
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: 


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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 5 6  of 1 2 7  
C o nfi d e nti al  
 
After t he i nitial i nf usi o n of st u d y dr u g a n d pri or t o e nr olli n g i n t he A K 0 0 2 -0 1 6 X e xte nsi o n  
st u d y (if a p plica ble), res ults of t he assess me nts n ote d bel o w will n ot be pr o vi de d t o t he 
I n v esti gat or a n d S p o ns or u ntil after data bas e l oc k s o as t o n ot i ntr o d uce bias. T he res ults 
will be re 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 escalat e d as a p pr o priat e.  
–  Differe 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 yt es, a n d 
l y m p h oc ytes.  
–  E n u merati o n of e osi n o p hils a n d  
 fr o m D a y 1 6 9 E G D bi o psies.  
Ot her t ha n u n der t he c o n diti o ns descri be d a b o ve, t he st u d y bli n d will be re v eale d o n c o m pleti o n 
of t he st u d y as n ote d i n Secti o n 1 6. 4 . 
1 0. 4  
Bre a ki n g t he Bli n d  
Brea ki n g t he  bli n d i n a cli nical trial o n a n e mer ge n c y b asis b y t h e site s h o ul d o nl y occ ur w h e n 
k n o wle d ge of t he tr eat me nt t o w hic h a s u bject was all ocate d w o ul d ha ve i m plicati o ns f or t he 
e mer ge n c y me dical ma n a ge m e nt of t he s u bject or if re q uire d f or re g ulat or y re p ort i n g, or if t here 
is a pre g na n c y d uri n g t he pre g na nc y re p orti n g peri o d. If necessar y, e mer ge nc y brea ki n g of t he 
bli n d ca n be c o n d u cte d t hr o u g h t h e I R T b y re gist ere 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 nt act t h e Me dical M o nit or bef ore 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, p ers o n c o n d ucti n g t h e 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 rec or de d.  
1 1.  St u d y Pr oce d ures a n d G ui deli nes  
Ta ble 1  pr o vi des t he s c he d ule of e ve nts de pi cti n g t he re q uir e d testi n g pr oce d ures t o be 
perf or me d f or t he d urati o n of t he st u d y.  
W he n m ulti ple e val uati o ns are sc h e d ul e d at t he s a me ti me p oi nt, t he pri orit y f or eac h will be as 
f oll o ws:  
 
(self-a d mi nistere d f or mat) s h o ul d be c o m pl ete d at t he be gi n ni n g of t he st u d y visit 
bef ore a n y ot her assess m e nts or pr oce d ures.  
 
P R O q uesti o n naire s h o ul d be c o m plete d b y eac h s u bjec t dail y (at a p pr o xi matel y t h e sa me 
ti me eac h da y) d uri n g t he scree ni n g, tr eat me nt, a n d f oll o w-u p peri o ds.  
 
Vital si g ns will be o btai n e d after t he s u bject has b ee n at r est f or ≥5 mi n utes.  
 
P h ysical e x a mi nati o ns ca n be perf or me d a n d uri ne sa m ples ca n be c olle cte d eit her bef ore or 
after ot her e val u ati o ns, u nless ot her wise s pecifie d.  
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 5 7  of 1 2 7  
C o nfi d e nti al  
1 1. 1  
Diet ar y a n d Lif est yle Restricti o ns  
Patie nts s h o ul d mai ntai n t he sa me diet a n d f o o d restricti o ns fr o m t he scree ni n g visit t hr o u g h t he 
E n d -of -St u d y visit. C o m plia nce wit h pre vi o us di etar y a n d lifest yle restricti o ns will be ca pt ure d 
i n t he e C R F at eac h st u d y visit. 
1 1. 2  
P h ar m a c o d y n a mi c/ Effic ac y -Rel ate d Pr o ce d ures  
1 1. 2. 1  
E G/ E o D P R O Q uesti o n n aire  
A n electr o nic v ersi o n of t he E G/ E o D P R O Q uesti o n naire ( A p pe n di x 1 ) will be  c o m plete d dail y 
at a p pr o xi matel y t he sa m e ti me of da y, b y t he pati e nt, t hr o u g h o ut t he st u d y.  
Patie nts will n ot be a ble t o c o m plete a q uesti o n naire m ore t ha n 2 4 h o urs aft er it is d ue a n d will 
o nl y be a ble t o g o bac k a n d ma ke c orrecti o ns or c ha n ges t o t he data ori gi n all y e nt ere d wit h t he 
a p pr o val of t he I n vesti gat or a n d E D C ve n d or. T h e P R O 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 P R O s yste m of t h e E D C.  
A pa per versi o n of t he P R O Q uesti o n naire is a vaila ble t o patie nts i n case t he y a re n ot a ble t o 
c o m plete t he ele ctr o nic v ersi o n f or a s h ort peri o d of ti me. O nl y 1 P R O s h o ul d be c o m plete d per 
da y a n d t he recall peri o d s h o ul d n ot be a n y m or e t ha n a p pr o xi matel y 2 4 h o urs l o n g. T his 
i nf or mati o n will be ma n uall y ca pt ure d a n d e ntere d  t he E D C b y t he st u d y sit e.  
If patie nts ha ve a hist or y of c o nc o mita nt at o pic der matitis or ast h ma, a n e xtra q uesti o n will be 
p o p ulate d f or eac h rele va nt c o n diti o n o n t he e P R O we bsite f or t he patie nt t o c o m plete dail y. 
All  patie nts will recei ve a n e xtra q u esti o n a b o ut d ys p ha gia d uri n g scree ni n g, a n d p atie nts wit h a 
wee kl y a v era ge > 3 o n at least 2 wee ks d uri n g s cree ni n g will c o nti n ue recei vi n g t his q uesti o n 
after e nr oll me nt i nt o t he st u d y. A pa p er versi o n of t hese q uesti o ns ( A p p e n di x 1 0 ) is a vaila ble, 
s h o ul d t he we bsite n ot be accessi ble, or t he patie nt n ot ha ve inter net access.  
1 1. 2. 2  
 
A n electr o nic v ersi o n of t he 
 (A p pe n di x 2 ) will be c o m plete d b y t h e patie nt 
at t he scree 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 D a y  1 9 7 or 3 5 ( ± 3) da ys a n d 5 6 ( ±) 3 da ys after l ast d ose of st u d y dr u g if E T. 
A  pa per versi o n of t his q uesti o n naire will als o be a vaila ble f or c o m pleti o n i n case t he el ectr o nic 
q uesti o n naire is n ot a vail a 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 electr o nic v ersi 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 electr o nic v ersi o n of t he 
 
C CI
C CI
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 5 8  of 1 2 7  
C o nfi d e nti al  
 (A p pe n di x 8 ) will be c o m plete d b y t he patie nt o n Scree ni n g 
Da y  1 8  as w ell as o n S t u d y D a y 7 a n d Da y 2 8. A pa per versi o n of t hese q u esti o n naires will als o 
be a vaila ble f or c o m pleti o n i n case t he el ectr o nic q uesti o n naire is n ot a vail a 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  
Es o p h a g o -G astr o -D u o de n osc o p y wit h Bi o ps y  
A n E G D wit h bi o ps y will be perf or m e d d uri n g t he scree ni n g p eri o d a n d o n Da y 1 6 9 ( ± 3 da ys) or 
2 8 ( ± 3) da ys after t he 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 dat e 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 t h e last d ose, e ve n if t his d oes  n ot  fall o n Da y 1 6 9  ( ± 3 da ys). Bi o ps y sa m ples 
will be c ollecte d acc or di n g t o sta n dar dize d i nstr ucti o ns a n d will be se nt t o t he ce ntral la b orat or y 
( or desi gnee) f or fi xi n g a n d stai ni n g. A bli n de d ce ntral rea d er will re p ort, a m o n g ot her t hi n gs, 
ma xi m u m n u m ber of e osi n o p hils per h pf  a n d ma xi m u m n u m ber of tr y ptas e -p ositi ve mast cells 
per h pf, a n d gastric bi o psies will be gra de d usi n g t he S y d ne y S yste m o n i nfla m mati o n, 
meta plasia, atr o p h y, a n d reacti ve gastr o pat h y. T h e Mars h Scale Classificati o n will be use d t o 
gra de d u o de n al sa m ples.  
P os t-treat me nt E G D res ults will n ot be pr o vi de d t o t he I n v esti gat or a n d S p o ns or u ntil after 
data base l oc k. T he Safet y M o nit or will re vie w t h e E G D res ults a n d re p ort a n y iss ues f or 
escalati o n t o t he Me dic al M o nit or a n d t he cli nical site, as a p pr o priat e, w hile mai ntai ni n g t he 
bli n d.  
T he scree ni n g E G D will be use d t o deter mi ne t h e f oll o wi n g i ncl usi o n/e xcl usi o n criteria, a n d t he 
res ults m ust be a vaila ble fr o m t he ce ntr al rea der bef ore t h e patie nt’s eli gi bilit y ca n b e verifie d.  
 
I n cl usi o n Criteri o n  # 3: Baseli ne e n d o sc o pi c bi o ps y wit h > 3 0 e osi n o p hils/ h pf i n 5 h pf i n t he 
st o mac h a n d/ or > 3 0 e osi n o p hils/ h pf i n 3 h pf i n t he d u o de n u m.  
 
E x cl usi o n  Criteri o n  # 5: Acti ve Helic o b a cter pyl ori  i nfecti o n, u nless treate d a n d c o nfir me d 
t o be ne gati ve pri or t o r a n d o mizati o n a n d hist ol og y per re p eat E G D a n d s y m pt o ms still 
q ualif y f or e nr oll me nt aft er treat me nt.  
N ote : A dia g n osis of acti ve H.  pyl ori at scree ni n g ma y b e treate d wit h sta n dar d t h era pies 
a n d a re p eat E G D c o m pl ete d pri or t o e nr oll me nt  t o verif y t hat hist ol o g y criteria are 
still met a n d s y m pt o ms r e mai n c o nsiste nt . If H.  p yl ori  is still prese nt o n re peat E G D 
b ut U B T a n d ot her cli nic al assess me nts of acti ve i nfecti o n are ne gati ve,  t he patie nt 
ma y b e ra n d o mize d i nt o t he st u d y.  
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 59 of 127 
Confidential 
11.2.5 
Complete Blood Count with Differential 
Blood will be obtained for complete blood count (CBC) with differential at the screening visit, as 
well as predose and 1 hour (±15 minutes) postdose on Days 1, 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 blood sample will be processed and shipped in accordance with laboratory manual 
and lab kit 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  
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, 29, 57, 85, 113, 141, 176, 197, and 225 or 35, 56, and 84 (±3) days past 
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 Review 
During the screening visit the Investigator or designee will ask the patient about the various 
treatments or methods of symptom control that they have tried in relation to their EG/EoD 
symptoms. These may be under the supervision of a doctor or self-attempted by the patient. 
These may include medications (prescription or OTC), food type/eating avoidance or adaptive 
behaviors, as well as alternative medicine (i.e., acupuncture or hypnotic therapy). 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 60 of 127 
Confidential 
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 in 
AK002-016X if patient enters the AK002-016X extension study.  
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, 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 for 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 Day 176 (±3), Day 197, and Day 225 (±3) 
or 35, 56, and 84 (±3) days after last dose of study drug if ET. 
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 AK002-016 study and a duplicate sample will not be 
collected.  


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 61 of 127 
Confidential 
11.3.5 
Symptom-Directed Physical Examination 
A symptom-directed physical exam, an examination of reported or observed subject 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 trial, 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. Please refer to the schedule of events in Table 1. 
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 1. Investigators may have additional laboratory tests performed for 
the purpose of planning treatment administration or following AE or abnormal lab 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 
following clinical safety laboratory tests.  
Clinical laboratory testing may be performed locally if the site thinks the central laboratory may 
not be able to provide results in a timely fashion due to staff reductions, shipping issues, or other 
factors associated with the COVID-19 pandemic. The site will strive to use the central laboratory 
whenever possible. 


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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 63 of 127 
Confidential 
11.5.1 
Pregnancy Test and Follicle-Stimulating Hormone 
A serum pregnancy (hCG) test will be completed for all patients of childbearing potential. 
Women who are surgically sterile (tubal ligation, 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 post-menopausal 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 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 serious adverse 
event (SAE) experienced during pregnancy must be reported on the SAE Report Form.  
11.5.2 
Urinalysis 
Urine will be obtained for urinalysis at screening and on Days 1, 29, 57, 85, 113, 141, 176, and 
197 or 35 and 56 (±3) days after last dose of study drug if ET. 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.  
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. 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 64 of 127 
Confidential 
11.5.4 
Anti-AK002 Antibodies 
Blood will be collected for determination of ADA at screening, on Days 8, 15, 29, 57, 85, 113, 
and 141, and on Days 169, 176, 197, and 225 or 28, 35, 56, and 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 
pre-dose 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 pre-dose 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. 
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. A positive result could indicate past/resolved infection, and a 
patient may be enrolled into the study with a positive Strongyloides stercoralis results as long as 
their ova and parasite test is negative for current infection and the Investigator has no clinical 
indication to believe active infection is present.  


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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 6 6  of 1 2 7  
C o nfi d e nti al  
 
A n E G D wit h bi o ps y d o es n ot nee d t o be c o m plete d f or A K 0 0 2 -0 1 6 s cree ni n g  i n 
acc or da nce wit h  I ncl usi o n Criteri o n 3: “ Pri or E G D ma y b e use d f or eli gi bilit y as l o n g as t he 
E G D occ urre d wit hi n 3 0 da ys of t he first scree ni n g visit f or t he A K 0 0 2 -0 1 6 st u d y a n d was 
perf or me d a n d ce ntrall y assesse d as f or t he A K 0 0 2 -0 1 6 st u d y. ” 
A n y testi n g re q uire d f or t he A K 0 0 2 -0 1 6 st u d y a n d n ot c o m plete d d uri n g t h e A K 0 0 2 -0 1 4 st u d y 
scree ni n g m ust be c o m pl ete d pri or t o e nr oll me nt i n t he A K 0 0 2 -0 1 6  st u d y.  
T he A K 0 0 2 -0 1 6 
 s h o ul d be c o m plete d b y t he p atie nt pre d ose o n Da y 1.  
St o ol testi n g s h o ul d be re peate d f or t he A K 0 0 2 -0 1 6  st u d y i n t he e ve nt of cli nical s us pici o n of 
hel mi nt hic/ parasitic i nfecti o n or if t he patie nt has tra vele d t o areas w here parasitic i nfecti o ns are 
e n de mic si nce t he A K 0 0 2 -0 1 4 st o ol testi n g  was d o ne .  
1 2.  E v al u ati o ns a n d Pr oce d ures b y Visit  
E val uati o ns a n d pr oce d ures b y visit are s h o w n i n Ta ble 1 . 
Ge neral I nf or m ati o n:  
 
All rec or 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 ures f or scree ni n g ma y b e perf or me d o ver t he c o urse of m ulti ple visits pri or t o t he 
first i nf usi o n. 
1 2. 1  
Scree ni n g Peri o d  
1)  
O btai n writte n i nf or me d c o nse nt.  
2)  
Assi g n t he partici pa nt a PI D.  
3)  
Be gi n t he c ollecti o n of S A E  relate d t o a n y scree ni n g acti vities. 
4)  
C ollect de m o gra p hics a n d me dical hist or y.  
5)  
Rec or d pri or a n d c o nc o mita nt me dicati o ns.  
6)  
Deter mi ne b o d y w ei g ht a n d hei g ht.  
7)  
Acti vate patie nt a ccess t o e P R O q uesti o n naire p ort al 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 Teac hi n g T o ol t o i nstr uct t he 
patie nt o n use of t he el ectr o nic platf or m ( A p pe n di x 7 ). 
8)  
 t o b e c o m pleted b y t he patie nt.  
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 6 7  of 1 2 7  
C o nfi d e nti al  
9)  
Perf or m baseli ne di et ass ess me nt . 
1 0)  C o m plete pre vi o us treat me nts re vie w . 
1 1)  O btai n vital si g ns bef ore bl o o d dra ws a n d after patie nt at rest ≥5 mi n utes.  
1 2)  Perf or m a c o m plet e p h ysical e x a mi nati o n.  
1 3)  O btai n a 1 0 -lea d or 1 2-le a 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)  C B C wit h differe ntial  
b)  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 d es 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 ret 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 scree ni n g E G D wit h bi o ps y f oll o wi n g pr oce d ures pr o vi de d b y Alla k os a n y ti me 
d uri n g t he s cree ni n g p eri o d.  
1 7)  
 t o be self-c o m plete d b y patie nt o n scree ni n g Da y 1 8  ( n ot a cli nic visit).  
1 8)  Usi n g res ults fr o m t he Ce ntral Hist ol o g y Rea der, c o nfir m t he e o si n o p hil c o u nt fr o m t he 
gastri c a n d/ or d u o de n al bi o psies q ualif y t he patie nt f or t he st u d y a n d n o e x cl usi o nar y 
criteria are f o u n d o n t he E G D.  
1 2. 2  
Pri o r t o D a y 1  
T he f oll o wi n g pr oce d ures will be perf or me d pri or t o Da y 1:  
 
Patie nt s h o ul d self -a d mi nister 6 0 m g or al pre d nis o ne ( or alter nati ve pre me dicati o n 
a p pr o ve d b y t he M e 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 
re me m ber w hat ti me t he y t o o k t he pre me dicati o n.  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 6 8  of 1 2 7  
C o nfi d e 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 Es relate d t o scree ni n g pr oce d ures.  
b)  C o nfir m c o nti n ui n g eli gi bilit y.  
c)  D oc u me nt a n y c h a n ges t o healt h stat us.  
d)  D oc u me nt a n y c h a n ges t o c o nc o mita nt me dicati o ns.  
e)  D oc u me nt a n y c h a n ges t o baseli ne diet.  
f) 
. 
g)  C o nfir m 
 was c o m plete d electr o ni call y o n scree ni n g Da y 1 8. If it was n ot 
c o m plete d ha ve p atie nt c o m plete a pa per versi o n of t he q uesti o n naire.  
h)  D eter mi ne b o d y w ei g ht.  
i) Uri ne f or uri nal ysis.  
j) Perf or m uri ne pre g na n c y test (if patie nt is of c hil d beari n g p o te ntial). 
k ) 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. 
l) Perf or m s y m pt o m -dir ect e d p h ysic al e xa m, if nee d e d.  
m ) Bl o o d f or C B C wit h differe ntial.  
n ) Bl o o d f or C he mistr y.  
2)  
Pri or t o ra 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 w ee kl y 
T S S of disease acti vit y rec or de d d uri n g t he s cree ni n g peri o d i n or der t o stratif y patie nts t o 
T S S ≥2 8 or T S S < 2 8 a n d w het her t he patie nt has a n E o D -o nl y di a g n osis , as i de ntifie d b y 
t he scree ni n g E G D. T he st u d y c o or di n at or or desi g nee will e nter t he hi g h est 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 stratif y t he patie nt, as well as b o d y wei g ht a n d PI D t o assi g n 
kit(s).  
3)  
T he I R T s yst e m will t he n ra n d o ml y assi g n t he p atie nt t o A K 0 0 2 at a d ose of 1  m g/ k g (first 
d ose) 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 pr e p are t he i nf usi o n, t he d os e t o pre pare 
( 1 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 h ar macist 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. T he 
fi nal c o m bi ne d v ol u me of t he I V ba g of st u d y dr u g + 0. 9 % Na Cl will be 1 2 0  m L.  
N ote : 1 0 0  m L  of t h e calc ul ate d d ose of st u d y dr u g will be a d mi nistere d t o t he pati e nt. 
T he  e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he pre parati o n of 
t he I V li ne at t he be dsi d e or t o be left o ver i n t he i nf usi o n ba g. 
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 6 9  of 1 2 7  
C o nfi d e nti al  
5)  
I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o v er at least 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 u al f or i nf usi o n rates. Rec or d t he st art 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 af ter t he start of i nf usi o n. 
c)  If a na p h yl a xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas m a hista mi ne 
le vel a n d tr y ptase wit hi n 1– 2 h o urs of t he o nset of s y m pt o ms. Als o, a n u nsc he d ule d 
A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge ni cit y -relate d A E  is s us pecte d. 
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 C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n.  
c)  O bser ve t he p atie 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 p e n di x 8 ) 
2)  
 (A p p e n di x 9 ) 
1 2. 5  
D a y 8 ( ± 2)  
1)  
C B C wit h differe ntial  
2)  
C he mistr y  
3)  
Bl o o d f or A D A  
4)  
Bl o o d f or P K  
1 2. 6  
D a y 1 5 ( ± 2)  
1)  
C B C wit h differe ntial  
2 ) 
C he mistr y  
3 ) 
Bl o o d f or A D A  
4 ) 
Bl o o d f or P K  
1 2. 7  
D a y 2 8 ( n ot a Cli nic Visit)  
1)  
 (A p p e n di x 8 ) 
2)  
 (A p p e n di x 9 ) 
C CI
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 7 0  of 1 2 7  
C o nfi d e nti al  
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 h a 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 n y a d diti o nal q uesti o ns).  
e)  
 
f) Deter mi ne b o d y w ei g ht.  
g)  Uri nal ysis  
h)  Perf or m uri ne pre g na n c 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 ect e d p h ysic al e xa m, as nee de d.  
k)  C B C wit h differe ntial  
l) 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 ac cesse 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 h ar macist will pre pare st u d y dr u g usi n g t he c urre nt b o d y wei g ht o btai ne 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 v er at least 3 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 u al f or i nf usi o n rates. Rec or d t he st art 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 yl a xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas m a hista mi ne 
le vel a n d tr y ptase wit hi n 1– 2 h o urs of t he o nset of t he s y m pt o ms. Als o, a n u nsc he d ule d 
A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge ni cit y -relate d A E  is s us pecte d. 
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 C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n.  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 7 1  of 1 2 7  
C o nfi d e nti al  
c)  O bser ve t he p atie nt f or at least 1 h o ur after t he e n d of t he i nf u si 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 h a 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 pl ia nce (i ncl u di n g a n y a d diti o nal q uesti o ns). 
e)  
 
f) Deter mi ne b o d y w ei g ht.  
g)  Perf or m uri ne pre g na n c 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 ect e d p h ysic al e xa m, as nee de d.  
j) C B C wit h differe ntial  
k)  C he mistr y  
l) Uri nal ysis  
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 h ar macist or desi g nee will pre p are  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 v er at least 2 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 u al f or i nf usi o n rates. Rec or d t he st art a n d st o p ti mes of t he i nf usi o n 
i ncl u di n g a n y ti mes t he i nf usi o n is i nterr u pte d. 
b)  C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of i nf usi o n.  
c)  If a na p h yl a xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas m a hista mi ne 
le vel a n d tr y ptase wit hi n 1– 2 h o urs of t he o nset of s y m pt o ms. Als o, a n u nsc he d ule d 
A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge ni cit y -relate d A E  is s us pecte d. 
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 7 2  of 1 2 7  
C o nfi d e nti al  
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 C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n.  
c)  O bser ve t he p atie 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 h a 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 n y a d diti o nal q uesti o ns)  
e)  
. 
f) Deter mi ne b o d y w ei g ht.  
g)  Uri nal ys is 
h)  Perf or m uri ne pre g na n c 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 ect e d p h ysic al e xa m, as nee de d.  
k)  C B C wit h differe ntial  
l) 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 h ar macist 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 d e 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 v er at least 2 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 u al f or i nf usi o n rates. Rec or d t he st art 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 CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 7 3  of 1 2 7  
C o nfi d e nti al  
c)  If a na p h yl a xis is s us pecte d, a sa m ple of bl o o d s h o ul d be o btai ne d f or plas m a hista mi ne 
le vel a n d tr y ptase wit hi n 1– 2 h o urs of t he o nset of 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 b tai ne d if a n i m m u n o ge ni cit 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 C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n.  
c)  O bser ve t he p atie nt f or at l east 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 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 h a 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 n y a d diti o nal q uesti o ns).  
e)  
. 
f) Deter mi ne b o d y w ei g ht.  
g)  Uri nal ysis  
h)  Perf or m uri ne pre g na n c 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 ect e d p h ysic al e xa m, as nee de d.  
k)  C B C wit h differe ntial  
l) 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 h ar macist 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 d e d b y t he I R T.  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 7 4  of 1 2 7  
C o nfi d e nti al  
4)  
I nf usi o n of St u d y Dr u g: 
a)  I nf use 1 0 0 m L of st u d y dr u g o v er at least 2 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 u al f or i nf usi o n rates. Rec or d t he st art 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 yl a xis is s us pecte d, a sa m ple of bl o o d sh o ul d be o btai ne d f or plas m a hista mi ne 
le vel a n d tr y ptase wit hi n 1– 2 h o urs of t he o nset of s y m pt o ms. Als o, a n u nsc he d ule d 
A D A bl o o d sa m ple ma y be o btai ne d if a n i m m u n o ge ni cit 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 u tes of t he e n d of t he i nf usi o n. 
b)  C ollect C B C wit h differe ntial 1 h o ur ( ± 1 5 mi n utes) after t h e e n d of t h e i nf usi o n.  
c)  O bser ve t he p atie 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 h a 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 n y a d diti o nal q uesti o ns)  
e)  
. 
f) Deter mi ne b o d y w ei g ht.  
g)  Uri nal ysis  
h)  Perf or m uri ne pre g na n c 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 ect e d p h ysic al e xa m, as nee de d.  
k)  C B C wit h differe ntial  
l) C he mistr y  
m)  Bl o o d f or P K  
n)  Bl o o d f or A D A  
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 75 of 127 
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 weight obtained at the visit 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 2 hours 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 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. 
12.13 Day 169 (±3) or 28 (±3) Days after Last Dose of Study Drug if ET – Follow-up EGD 
1) 
Patient should arrive fasting for the EGD procedure as specified by instructions from the 
EGD provider. 
2) 
Blood Draws: 
a) Blood for CBC with differential 
b) Blood for Chemistry 
c) Blood for PK 
d) Blood for ADA 
3) 
Collect AE, SAE, and changes in baseline diet. Collect all concomitant medications 
provided to the patient during the EGD. 
4) 
Perform EGD with biopsy following procedures provided by Allakos and all EGD facility 
standard operating procedures.  


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 7 6  of 1 2 7  
C o nfi d e nti al  
F or E a rl y Ter mi n ati o n:  Perf or m t he E G D 2 8 ( ± 3) da ys after t he last d ose of st u d y dr u g or pri or 
t o t his, if necessar y, t o e ns ure c o m plia nce wit h t he visit. If patie nt disc o nti n ues t he st u d y m or e 
t ha n 2 8 da ys after t he last d ose of st u d y dr u g, p erf or m t he E G D as s o o n as p ossi ble.  
If D a y 1 4 1 (I nf 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 E G D o n Da y  1 6 9 
b ut rat her o n a d a y t hat is 2 8 ( ± 3) d a ys after t he Da y 1 4 1 i nf usi 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 St 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 h a n ges t o c o nc o mita nt me dicati o n s. 
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 n y a d diti o nal q uesti o ns).  
5)  
. 
6)  
Deter mi ne b o d y w ei g ht.  
7)  
C ollect vital si g ns.  
8)  
Perf or m s y m pt o m -dir ect e d p h ysic al e xa m, as nee de d.  
9)  
Bl o o d Dra ws:  
a)  Bl o o d f or C B C wit h differe ntial  
b)  Bl o o d f or C he mistr y  
c)  Bl o o d f or P K  
d)  Bl o o d f or A D A  
e)  Bl o o d f or I g E  
1 0)  Uri nal ysis a n d uri ne pre g na nc y test (if patie nt is of c hil d beari n g p ote ntial) 
1 1 ) Patie nts w h o e nr oll i n t he A K 0 0 2 -0 1 6 X e xte nsi o n st u d y will be gi n  e xte nsi o n st u d y d osi n g 
1  d ay after  c o m pleti n g th e Da y 1 7 6 pr oce d ures f or Pr ot oc ol A K 0 0 2 -0 1 6. Patie nt s ma y si g n 
c o nse nt f or t he A K 0 0 2-0 1 6 X st u d y d uri n g partici pati o n i n t he A K 0 0 2 -0 1 6 st u d y a n d ma y 
recei v e t he pre me dicati o n f or t he first A K 0 0 2 -0 1 6 X d ose as s o o n as all Da y 1 7 6 pr oce d ures 
ha ve bee n c o m plete d i n t he mai n st u d y. If patie nts ca n n ot start t he e xte nsi o n st u d y 1  da y 
after t he Da y 1 7 6 visit, t he y will c o nti n ue partici pati o n i n t he mai n st u d y. If patie nts ca n n ot 
start t he e xte nsi o n st u d y wit hi n 2 8 da ys of t he Da y 1 7 6 visit i n t he mai n st u d y, t he Da y 1 9 7 
visit will occ ur.  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 7 7  of 1 2 7  
C o nfi d e nti al  
F or E a rl y Ter mi n ati o n:  Perf or m t he visit 3 5 ( ± 3) da ys after t h e last d ose of st u d y dr u g or pri or 
t o t his, if 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 3 5 da ys after t he last d ose of st u d y dr u g, p erf or m t he visit as s o o n as p ossi ble. If o nl y o n e 
E T visit is p ossi ble, E G D a n d F oll o w -u p Visit  1 ma y o cc ur o n t h e sa me da y. Bl o o d dra ws s h o ul d 
occ ur pri or t o E G D me di cati o ns, if p ossi bl e.  
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 h a 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 w ei g ht.  
6)  
C ollect vital si g ns.  
7)  
Perf or m s y m pt o m -dir ect e d p h ysic al e xa m, as nee de d.  
8)  
Uri nal ysis a n d uri ne pre g na nc y test (if patie nt is of c hil d beari n g p ote ntial) 
9)  
Bl o o d Dra ws:  
a)  Bl o o d f or C B C wit h differe ntial  
b)  Bl o o d f or C he mistr y  
c)  Bl o o d f or P K 
d)  Bl o o d f or A D A  
1 0)  Patie nts o pti n g t o e nr oll i n t he A K 0 0 2 -0 1 6 X e xte nsi o n st u d y after t he Da y 1 9 7 visit will 
be gi n e xte nsi o n st u d y d osi n g wit hi n 2 8 da y s of  c o m pleti n g t he Da y 1 9 7 pr oce d ures f or 
Pr ot oc ol A K 0 0 2 -0 1 6. If patie nts ca n n ot start t he e xte nsi o n st u d y wit hi n 2 8 da ys of t he 
Da y  1 9 7 visit, t he y will c o nti n ue partici pati o n i n  t he mai n st u d y. If patie nts ca n n ot start t he 
e xte nsi o n st u d y wit hi n 2 8 da ys of t he Da y 1 9 7 visit i n t he mai n st u d y, t he Da y 2 2 5 visit 
will occ ur  
F or E a rl y Ter mi n ati o n:  Perf or m t he visit 5 6 ( ± 3) da ys after t h e last d ose of st u d y dr u g or pri or 
t o t his, if 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 5 6 da ys after t he last d ose of st u d y dr u g, p erf or m t he visit as s o o n as p ossi ble.  
C CI


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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 82 of 127 
Confidential 
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 
The Investigator will use their clinical judgment as well as the guidelines laid out in the NCI 
CTCAE Version 5.0 (or most current version) tables (Table 2 and Appendix 4) to assess the 
intensity of each AE and SAE. 
Table 2 
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 adverse event. 
* 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 3 to assess 
the relationship between study drug and AE. 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 83 of 127 
Confidential 
Table 3 
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 4 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 4 
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.  


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 84 of 127 
Confidential 
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 early termination 
will be followed by the Investigator until event resolution, the AE is otherwise explained, not 
considered clinically significant by the Investigator, or the subject is lost to follow-up. 
All AE identified, whether serious or non-serious, will be recorded in the AE eCRF beginning 
after the first administration of study drug and ending on Day 225 (±3) or 84 (±3) days after last 
dose if patient is not enrolling in the AK002-016X extension study, or until the start of the first 
dose on Day 1 of the extension study, if enrolling in AK002-016X, unless otherwise directed by 
Allakos. 
Whenever appropriate, the CTCAE (v. 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.  
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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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 86 of 127 
Confidential 
Serious adverse events 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 the last dose if patient is not enrolling in the AK002-016X extension 
study, or until the start of the first dose on Day 1 of extension study, if enrolling in 
AK002-016X, 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. The patient 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.  
Any congenital abnormalities noted at birth in the offspring of a patient who received AK002 
will be reported as an 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 and ending on Day 225 (±3) or 84 (±3) days 
after last dose if patient is not enrolling in the AK002-016X extension study, or until the start of 
the first dose on Day 1 of the extension study, if enrolling in AK002-016X, 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 “adverse event of special interest.”  
An AESI that also qualifies as a SAE (per Section 13.2) must also be reported as a SAE in 
accordance with Section 13.7.2. Adverse events of special interest that are also SAE must be 
recorded in the AE eCRF and designated as both “serious” and as an “adverse event of special 
interest.” These will be reported on the Sponsor-provided SAE forms and should be reported to 
the Sponsor within 24 hours of site awareness. 


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 8 7  of 1 2 7  
C o nfi d e nti al  
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 dress 
bel o w t o re p ort me dic al c o ncer ns or f or q uesti o ns re gar di n g safet y.  
 
Alla k os Me dical M o nit or  
 
 M D 
 
P h o ne:  
 
 
E mail:  
 
1 3. 9  
I n de pe n de nt D at a M o nit ori n g C o m mittee 
A n I n de pe n d e nt Data M o nit ori n g C o m mittee (i D M C) has bee n c o n v e ne d f or t his st u d y. T he 
i D M C will meet at esta blis he d i nter vals t hr o u g h o ut t he st u d y a n d will als o c o n ve ne as 
necessitate d b y d ata a n d/ or safet y re vie ws.  
1 3. 1 0  St u d y Wit h dr a w al Criteri 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 urre nce of a n e x cl usi o n criteri o n, w hic h is cli nicall y rele va nt a n d affects t he patie nt’s 
safet y, if disc o nti n uati o n is c o nsi dere d necessar y b y t he I n v esti gat or a n d/ or S p o ns or.  
 
Re b o u n di n g of e osi n o p h il c o u nts t o > 1 5 0 0/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/ L, a n d w h os e e osi n o p hil c o u nts were i nitiall y s u p presse d after 
st u d y dr u g 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 tra nsa mi nases ( A L T a n d/ or A S T) > 3 × U L N a n d t otal bilir u bi n > 2 × U L N 
(c o nfir me d b y s u bs e q ue nt re peat) wit h o ut a n alter nati ve e x pla nati o n.  
 
Ele vati o n of A L T or A S T > 3 × U L N (c o nfir me d b y re peat) wit h t he a p peara nce or 
w orse ni n g of s y m pt o ms felt b y t he I n v esti gat or t o be p ote ntiall y relate d t o h e patic 
i nfla m mati o n, s uc h as fati g ue, n a usea, v o miti n g, ri g ht u p per q ua dra nt pai n or te n der ness, 
fe ver, ras h. 
1 3. 1 1  St u d y St o p pi n g R ules  
T he st u d y ma y b e disc o nti n ue d pre mat urel y i n t he e ve nt of a n y of t he f oll o wi n g:  
 
A life -t hreate ni n g A E  t hat is p ossi bl y or pr o ba bl y relate d t o treat me nt.  
 
A fatal A E  t hat is p ossi bl y or pr o ba bl y relate d t o treat me nt.  
 
Ne w i nf or mati o n le a di n g t o u nfa v ora ble ris k -be nefit j u d g me nt of t he st u d y dr u g.  
 
S p o ns or’s decisi o n t hat c o nti n uati o n of t he trial is u nj ustifia ble f or me dical or et hical 
reas o ns.  
 
Disc o nti n uati o n of de vel o p me nt of t he S p o ns or’s st u d y dr u g.  
P P D
P P D
P P D
P P D


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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 89 of 127 
Confidential 
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 3 weeks of observation before the 
first IV 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% CI 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 160 patients will be enrolled.  
First Co-Primary Endpoint: A sample size of 80 patients per treatment group will have 
>99% power to demonstrate a greater proportion of responders in AK002 patients than in 
placebo patients, assuming the proportions of responders are 0.6 and 0.1 in AK002 and placebo 
groups, respectively.  
Second Co-Primary Endpoint: A sample size of 80 patients per group will provide 96% power 
to detect a statistically significant difference between AK002 and placebo in the mean reduction 
from baseline in TSS score, assuming a mean reduction of 16.1 points on AK002 versus 
8.7 points on placebo and a common standard deviation of 12.5 points (AK002-003 data on file). 
Eighty patients per group will provide 96% power to pick up a difference between placebo and 
AK002 of 7.4 in TSS with a mean Baseline TSS of 30 and a standard deviation (change from 
baseline) of 12.5. These assumptions are based on data observed in the Phase 2 AK002-003 
study.  
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. 


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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 91 of 127 
Confidential 
factors (Baseline TSS [<28 vs ≥28] and disease strata [EG ± EoD vs EoD]) to assess robustness 
of Fisher’s exact test results. 
The rationale for specifying Fisher’s exact test as the primary analysis as opposed to specifying 
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. 
The second co-primary endpoint will be analyzed by ANCOVA using the imputed data set 
outlined in the SAP. The LSM, SE, and 95% CI for each treatment group and for the between 
group difference will be derived from ANCOVA with treatment as a factor, and Baseline PRO 
TSS (continuous) and EoD without EG (categorical) 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.  
Two sensitivity analyses will be conducted to assess the departures from the missing at random 
(MAR) data assumption. The first sensitivity analysis will be 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 events 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 second sensitivity analysis will be based on the tipping point 
method. In this method, the missing biweekly TSS will be imputed with different adjustments for 
the active treatment subjects and placebo subjects under the MNAR assumption in search for a 
tipping point that reverses the study conclusion (i.e., p-value no longer <0.05 for the treatment 
effect). Detailed specifications for the analyses outlined above 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 specified in the synopsis. If 
at any point, the statistical test is not significant at 2-sided α=0.05 level, the hypothesis testing 
procedure will stop. 
For patients who provide gastric or duodenal only 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). For patients who provide both gastric and duodenal biopsies, the calculation will be 
based on the average count of the highest readings from the Day 169 biopsy that correspond in 
location (gastric or duodenal) to the location with the highest average count at baseline. The 
change in tissue eosinophil count from baseline to Day 169 will be analyzed using ANCOVA 


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 9 2  of 1 2 7  
C o nfi d e nti al  
wit h treat me nt as a fact or, a n d baseli ne e osi n o p hil c o u nts, Bas eli ne  P R O T S S, a n d d isease stat us 
as c o vari ates. T he L S M , S E, a n d 9 5 % CI f or i n di vi d ual treat me nt gr o u ps, a n d L S M, S E, 9 5 % CI, 
a n d p-val ue f or t he bet w ee n treat me nt differe n ce will be prese nte d.  
Pr o p orti o n of patie nts ac hie vi n g gastri c a n d/ or d u o de nal e osi n o p hil c o u nt of ≤1 c ell/ h pf will be 
a nal yze d usi n g Fis her’s e x act test si milar t o t he a nal ysis f or t h e first c o -pri mar y e n d p oi nt.   
Pr o p orti o n of treat me nt r es p o n ders defi ne d b y > 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 ≤4 cells per h pf i n 5 gastri c h pf a n d/ or m ea n e osi n o p hil c o u nt ≤1 5 cells per h pf i n 
3  d u o de nal h pf will be a n al yze d usi n g Fis her’s e x act test.  
Pr o p orti o n of patie nts wit h ≥5 0 % re 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 yz e d usi n g t he C M H test stratifie d b y t h e ra n d o mi zati 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 x e d 
effects f or bas eli ne val ue, treat me nt, wee k , a n d t h e treat me nt b y wee k i nteracti o n a n d all o w f or 
ra n d o m s u bject effects a n d ass u me a n u nstr uct ur e d c o varia n ce str uct ure. 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 a n d bet wee n-s u bj ect vari a nce esti mates . T he L S M  a n d t he 9 5 % CI f or t he 
bet wee n gr o u p differe nce will be esti mate d f or eac h wee k.   
T he e C D F a n d P D F pl ots will be prese nte d f or c h a n ge fr o m B aseli ne T S S sc ore at Wee ks 2 3 – 2 4 
stratifie d b y  
 a n d  
 s c ores. 
1 5. 6. 3  
E x pl or at or y A n al ys is 
A nal ysis of patie nts  wit h 
 will be carri e d o ut si milarl y usi n g  
 
 test. C ha n ge fr o m Baseli ne  
 
at W ee k 2 5 will be a nal yze d usi n g t he 
 si milar t o t he a nal ysis o utl i ne d a b o ve. 
C ha n ge fr o m bas eli ne  i n t he 
 will be s u m marize d b y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 9 3  of 1 2 7  
C o nfi d e nti al  
 will be a nal yze d usi n g 
 as descri b e d 
a b o ve. T he 
 a n d t he 
 f or t he bet wee n gr o u p c o m paris o n will be 
prese nte d f or t he 
 acr oss Wee k 1 t hr ou g h Wee k  2 4 a n d f or  
 at eac h wee k.  
T he 
 will be s u m me d u p t o deri ve t he  
 
 T he y will t he n be a nal yz e d usi n g t he 
 wit h 
 
 
1 5. 7  
S afet y A n al ysis  
A d vers e E ve nts: All A E  will be c o de d usi n g t h e Me dical Dicti o nar y f or R e g ul at or y Acti vities 
( Me d D R A) a n d will be classifie d b y M e d D R A s yste m or ga n class ( S O C) a n d preferre d t er m. 
Listi n gs will i ncl u de all A E  c ollecte d o n st u d y. T he s u m maries of A E  will be base d o n T E A E, 
defi ne d as a n A E  re p orte d i n t he cli nical data bas e wit h a date of o nset ( or w orse ni n g) o n or after 
t he start date of t he first I V i nf usi o n of t he st u d y me dicati o n.  
1 5. 7. 1  
Tre at me nt E mer g e 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 m arize d as f oll o ws:  
 
O ver vie w of T E A E t o i n cl u de  
–  N u m ber ( %) of patie nts w h o re p orte d at least 1  T E A E o verall, b y se v erit y, a n d b y 
relati o ns hi p 
–  N u m ber ( %) of 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 l ea di n g t o treat me nt 
disc o nti n uati o n  
–  N u m ber ( %) of patie nts w h o re p orte d at least 1  T E A E of s peci al i nterest ( T E A E SI)  
 
T E A E b y preferre d ter m  
 
T E A E b y S O C a n d preferre d ter m  
 
T E A E b y m a xi m u m se verit y, S O C, a n d preferre d t er m  
 
T E A E b y S O C a n d preferre d ter m  a n d rel ati o ns hi p t o st u d y dr u g  
 
T E A E lea di n g t o wit h dra wal b y S O C a n d preferre d ter m  
 
Seri o us T E A E b y S O C a n d preferre d t er m  
 
T E A E SI b y S O C a n d preferre d ter m  
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 94 of 127 
Confidential 
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 (A., 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 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 


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17. Administrative, Ethical, and Regulatory Considerations 
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Amendment 4 
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Allakos Inc. 
Page 98 of 127 
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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 standard 
operating procedures 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.  
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 
standard operating procedures 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 (PCP) notified of their study participation. If yes, the 
PCP 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 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 99 of 127 
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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 standard operating procedures and policies of the EGD facility/investigational site.  
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 Study Registration 
This clinical study is registered on the Clinical Trial Registry Website, www.ClinicalTrials.gov 
as NCT #04322604. 
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. After randomization, 
patients at participating study sites will be compensated for each completed week of daily 
questionnaires as long as at least 4 questionnaires per week are completed. Patients 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.  


 
Protocol AK002-016 
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Allakos Inc. 
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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).  
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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Allakos Inc. 
Page 101 of 127 
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18. References  
Alhmoud T, Hanson J, Parasher G. Eosinophilic gastroenteritis: an underdiagnosed condition. 
Dig Dis Sci, 2016;61:2585–92. 
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. 
Food and Drug Administration. Guidance for industry E9 (R1): Statistical Principles for clinical 
trials: addendum: estimands and sensitivity analysis in clinical trials. ICH, May 2021. 
Hudson S, Herrmann H, Du J, Cox P, Haddad E, 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(6):1045-53. 
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. The American Journal of Gastroenterology, 2013;108:308–328. 
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. 


 
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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 1 6  
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1 9.  A p pe n dices  
1 9. 1  
A p pe n di x 1:  P R O Q uesti o n naire  
1 9. 2  
A p pe n di x 2:  
  
1 9. 3  
A p pe n di x 3:  Baseli ne Di et Assess me nt  
1 9. 4  
A p pe n di x 4:  C o m m o n Ter mi n ol o g y 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 Hist ol o g y  
1 9. 6  
A p pe n di x 6:  Sa m ps o n’s Criteria of A na p h yl a xis  
1 9. 7  
A p pe n di x 7:  e P R O Teac hi n g T o ol   
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 At o pic C o n diti o ns   
1 9. 1 1  A p pe n di x 1 1:  Pre vi o us Treat me nts 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 gical T esti n g Details   
 
 
C CI
C CI
C CI


 
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Allakos Inc. 
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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. 
 
 


 
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C CI


 
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Alla k os I nc.  
P a ge 1 0 8  of 1 2 7  
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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 1 0 9  of 1 2 7  
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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 1 1 0  of 1 2 7  
C o nfi d e nti al  
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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 1 1 1  of 1 2 7  
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Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
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C CI
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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 113 of 127 
Confidential 
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 gastritis (EG) and 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 EG/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  
Yes ☐ 
No ☐ 
due to your EG/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 EG/EoD? 
Yes ☐ 
No ☐ 
 
If Yes, please describe:  
 
 
 
 
v. 14Mar2020 
Page 1 of 1 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 114 of 127 
Confidential 
19.4 
Appendix 4: Common Terminology Criteria for Adverse Events v. 5.0 
Common Terminology Criteria for Adverse Events (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 x ULN 
and asymptomatic 
>2.0–5.0 × ULN 
with signs or 
symptoms; >5.0 x 
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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Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 119 of 127 
Confidential 
19.7 
Appendix 7: ePRO Teaching Tool 
 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 120 of 127 
Confidential 
19.7 
Appendix 7: ePRO Teaching Tool cont. 
 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 121 of 127 
Confidential 
19.7 
Appendix 7: ePRO Teaching Tool cont. 
 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 122 of 127 
Confidential 
19.7 Appendix 7: ePRO Teaching Tool cont. 
 


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 1 2 3  of 1 2 7  
C o nfi d e nti al  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 6  
A me n d me nt 4  
Date: 2 6  Oct  2 0 2 1  
Alla k os I nc.  
P a ge 1 2 4  of 1 2 7  
C o nfi d e nti al  
C CI


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 125 of 127 
Confidential 
19.10 Appendix 10: Additional Questions for Atopic Conditions  
 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 126 of 127 
Confidential 
19.11 Appendix 11: Previous Treatments 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 EG and/or EoD (sometimes called EGE) before 
participating in this study? 
Yes  
 
No 
 
2. 
Have you previously taken prescription medications specifically for the diagnosis of 
EG/EoD?  
Yes* 
 
No 
 
N/A, not previously diagnosed with EG/EoD 
 
 
If yes*please list:___________________________________________________________ 
 
All medications taken for EG/EoD or EG/EoD symptoms at any time should be listed on the 
Con-Med Log. 
3. 
Have you previously taken over-the-counter (OTC) medications for symptoms of EG/EoD 
(i.e., Zantac®, Tylenol®, Tums®)? 
Yes* 
 
No 
 
 
If yes*please list:___________________________________________________________ 
 
All medications taken for EG/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 EG/EoD?  
 
Yes* 
 
No 
 
 
If yes*please describe:_______________________________________________________ 
5. 
Have you previously tried changing your eating habits to help improve the symptoms of 
EG/EoD?  
Yes* 
 
No 
 
 
If yes*please describe:_______________________________________________________ 
6. 
Have you previously tried other methods to help improve the symptoms of EG/EoD 
(i.e., acupuncture, pressure point therapy)?  
Yes* 
 
No 
 
 
If yes*please describe:_______________________________________________________ 
Additional Comments  
 
 
 
 
 
_______________________________________________________ 
 
Name of Person completing the Previous Treatments Review 


 
Protocol AK002-016 
Amendment 4 
Date: 26 Oct 2021 
Allakos Inc. 
Page 127 of 127 
Confidential 
19.12 Appendix 12: Hepatitis B and Hepatitis C Serological Testing Details 
19.12.1 Hepatitis B Testing 
HBsAg positive patients are excluded. However, in case of past infections/vaccination in order to 
qualify, the patient’s testing status needs to align with the information in Table 5.  
Table 5 
Hepatitis B Reflex 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 
Anti-HCV positive and HCV-RNA positive patients are excluded. In order to qualify, the 
patient’s testing status needs to align with the information in Table 6.  
Table 6 
Hepatitis C Reflex Testing 
Non-Reactive 
Or 
Past Infection (Resolved) 
Anti- HCV 
Negative 
Anti- HCV 
Positive 
HCV RNA 
Negative 
 

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Page 1 of 59 
Statistical Analysis Plan for Protocol AK002-016 
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 Gastritis and/or Eosinophilic 
Duodenitis (formerly referred to as Eosinophilic Gastroenteritis) Who 
Have an Inadequate Response with, Lost Response to, or Were Intolerant 
to Standard Therapies 
Protocol Number 
AK002-016  
Protocol Version 
Amendment 4 
Protocol Dates 
Amendment 4 26 October 2021 
Amendment 3 
20 April 2021 
Amendment 2 
07 August 2020  
Amendment 1 
18 March 2020 
Original 
30 September 2019  
Study Drug 
AK002 (lirentelimab) 
Study Phase 
3 
IND Number 
135158 
Sponsor  
Allakos Inc., 975 Island Drive, Suite 201, Redwood City, CA 94065 USA 
SAP Version 
1 
SAP Date 
05 November 2021 
SIGN


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Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
Page 3 of 59 
Confidential 
Table of Contents 
Statistical Analysis Plan for Protocol AK002-016 .......................................................................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 ...................................................................................21 
4. 
Definitions ............................................................................................................................22 
4.1 
Terminology and Definitions ....................................................................................22 
4.2 
Target of Estimation ..................................................................................................23 


 
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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 .......................................................................................................24 
4.2.4 Intercurrent Events ........................................................................................24 
4.2.5 Strategy for Handling Intercurrent Events ....................................................24 
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 ..........................................................26 
5.3 
Adjustment for Covariates .........................................................................................29 
5.4 
Handling of Dropouts, Missing Data, and Data Discrepancies .................................29 
5.4.1 Missing 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 ........................................................................................................30 
5.6 
Timing of Data Analyses ...........................................................................................30 
5.7 
Multicenter Study ......................................................................................................31 
5.8 
Multiple Comparisons/Multiplicity Adjustment .......................................................32 
5.9 
Examination of Subgroups ........................................................................................32 
6. 
Statistical Analysis ...............................................................................................................32 
6.1 
Analysis Populations .................................................................................................32 
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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6.1.5 Primary Analysis Population .........................................................................33 
6.2 
Disposition of Subjects ..............................................................................................33 
6.3 
Protocol Deviations ...................................................................................................34 
6.4 
Demographics and Baseline Subject Characteristics ................................................34 
6.5 
Baseline Disease Characteristics ...............................................................................34 
6.6 
Medical History .........................................................................................................34 
6.7 
Electrocardiogram .....................................................................................................35 
6.8 
Pregnancy Test ..........................................................................................................35 
6.9 
Baseline Diet .............................................................................................................35 
6.10 
Treatments .................................................................................................................35 
6.10.1 Treatment Compliance and Extent of Exposure ............................................35 
6.10.2 Prior, Concomitant, and Newly Initiated Medications ..................................35 
6.11 
Analysis of Primary Efficacy Endpoints ...................................................................36 
6.11.1 Analysis of the First Co-Primary Endpoint ...................................................36 
6.11.2 Sensitivity Analysis of the First Co-Primary Endpoint .................................37 
6.11.3 Subgroup Analysis of the First Co-primary Endpoint ...................................37 
6.11.4 Analysis of the Second Co-Primary Endpoint ...............................................37 
6.11.5 Sensitivity Analyses of the Second Co-Primary Endpoint ............................37 
6.11.6 Supplementary Analyses ...............................................................................39 
6.12 
Analysis of Secondary Efficacy Endpoints ...............................................................39 
6.12.1 Change in Tissue Eosinophil Count ..............................................................39 
6.12.2 Proportion of Subjects Achieving Peak Gastric and/or Duodenal 
Intraepithelial Eosinophil Count of ≤1 Cell/hpf ............................................39 
6.12.3 Proportion of Treatment Responders .............................................................39 
6.12.4 Proportion of Subjects with ≥50% Reduction and ≥70% Reduction in 
TSS from Baseline to Weeks 23–24 ..............................................................40 
6.12.5 Change in Weekly TSS Over Time ...............................................................40 


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 6 of 5 9  
C o nfi de nti al  
6. 1 3  
A nal ysis of E x pl orat or y E n d p oi nts  ........................................................................... 4 0 
6. 1 3. 1  C ha n ge i n 
 .......................................................................... 4 0 
6. 1 3. 2  C ha n ge i n  
 ............................................................................................ 4 1  
6. 1 3. 3  S u bjects Ac hie vi n g 
 
 at Wee k  2 4 ..................................................................... 4 1 
6. 1 3. 4  C ha n ge i n 
 ............................................. 4 1 
6. 1 3. 5  
 
6. 1 3. 6  
 
6. 1 4  
A nal ysis of P har mac o ki netic E n d p oi nt ..................................................................... 4 2  
6. 1 5  
Safet y A nal yses  ......................................................................................................... 4 2 
6. 1 5. 1  A d verse E ve nts .............................................................................................. 4 2  
6. 1 5. 2  La b orat or y Test  ............................................................................................. 4 4 
6. 1 5. 3  Vit al Si g ns, Hei g ht a n d Wei g ht, a n d Ot her Safet y Meas ures ....................... 4 4  
6. 1 5. 4  Electr ocar di o gra m  ......................................................................................... 4 4 
6. 1 5. 5  P h ysical E xa mi nati o n  .................................................................................... 4 4 
6. 1 5. 6  A nal ysis of A nti -Dr u g A nti b o d y  ................................................................... 4 4 
7.  
V ali d ati o n  ............................................................................................................................. 4 4 
8.  
Refere nces  ............................................................................................................................ 4 5 
9.  
A p pe n dices  ........................................................................................................................... 4 6 
9. 1  
A p pe n di x 1: Effe ct of Missi n g Data o n t he Wee kl y Mea n of T S S  ........................... 4 7 
9. 2  
A p pe n di x 2: I nterc urre nt E ve nts ............................................................................... 4 9  
9. 3  
A p pe n di x 3: List of Ta bles, Fi g ures, a n d Listi n gs .................................................... 5 1  
9. 4  
A p pe n di x 4: E xa m ple S A S C o des ............................................................................. 5 9  
 
C CI
C CI
C CI
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 7 of 5 9  
C o nfi de nti al  
List of I n-Te xt T a bles  
Ta ble 1  
Sc he d ule of Assess me nts  ....................................................................................... 1 6 
Ta ble 2  
Ter mi n ol o g y a n d Defi niti o ns ................................................................................. 2 2  
Ta ble 3  
A nal ysis Wi n d o w R ules f or  
 ........................................................................ 2 7  
Ta ble 4  
A nal ysis Wi n d o w R ules f or Vital Si g n a n d La b orat or y Tests ............................... 2 7  
Ta ble 5  
A nal ysis Wi n d o w R ules f or P K C o nce ntrati o n a n d A D A ..................................... 2 8  
Ta ble 6  
A nal ysis Wi n d o w R ules f or Bl o o d Hista mi ne a n d Uri nal ysis ............................... 2 8  
Ta ble  7 
Sta n dar d Err ors f or t he Mea n Wee kl y T S S Diaries b y N u m ber of 
Dail y  Diaries  Missi n g A vera ge d o ver 5 0 0 Si m ulati o ns ........................................ 4 8 
 
C CI


 
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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) 


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 9 of 5 9  
C o nfi de nti al  
I V 
I ntra ve n o us  
L L N 
L o wer li mit of n or mal  
L L O Q  
L o wer li mit of q ua ntificati o n  
L S M 
Least s q uares mea n  
M A R  
Missi n g at ra n d o m 
M C A R  
Missi n g c o m pletel y at ra n d o m  
M C M C  
Mar k o v C hai n M o nte Carl o ( met h o d)  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
MI  
M ulti ple i m p utati o n (s) 
MI T T  
M o difie d i nte nt-t o-treat ( p o p ulati o n) 
M M R M  
Mi xe d M o del f or Re peate d Meas ures  
M N A R  
Missi n g n ot at Ra n d o m  
p- val ue  
Pr o ba bilit y val ue  
P D  
P har mac o d y na mics  
P E  
P h ysical e xa mi nati o n  
 
 
 
 
P K  
P har mac o ki netic(s)  
P P  
Per pr ot oc ol ( p o p ulati o n) 
P PI  
Pr ot o n p u m p  i n hi bit or(s) 
P R O  
Patie nt -re p orte d o utc o me 
P T  
Preferre d ter m  
S A E  
Seri o us a d verse e ve nt  
S A P  
Statistical A nal ysis Pla n  
S A S  
Statistical a nal ysis s yste m  
S D  
Sta n dar d de viati o n  
S E  
Sta n dar d err or(s)  
S D T M  
St u d y Data Ta b ulati o n M o del  
 
 
S O C  
S yste m or ga n class  
T E A E 
Treat me nt -e mer ge nt a d verse e ve nt (s) 
T E A E SI 
Treat me nt -e mer ge nt a d verse e ve nt (s) of s pecial i nterest 
T E S A E 
Treat me nt -e mer ge nt seri o us a d verse e ve nt (s) 
T L F 
Ta bles, listi n gs, a n d fi g ures 
C CI
C CI
C CI


 
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Statistical Analysis Plan – Version 1 
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Allakos Inc. 
Page 10 of 59 
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TSS 
Total Symptom Score 
ULN 
Upper limit of normal 
WHO 
World Health Organization 
WHODD 
World Health Organization Drug Dictionary 
 


 
Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
Page 11 of 59 
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Revision History 
Version Date 
Version Number 
Description 
05 Nov 2021 
1 
Initial document 
 
 


 
Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
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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 gastritis (EG) and/or 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 AK002-016 Amendment 4, dated 26 October 2021, 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 EG and/or 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 the following eosinophil counts: 
− EG: Mean eosinophil count ≤4 cells/hpf in 5 highest gastric hpf 
− EoD: Mean eosinophil count ≤15 cells/hpf in 3 highest duodenal hpf 
− EG + EoD: Mean eosinophil count ≤4 cells/hpf in 5 highest gastric hpf and mean 
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) comprises the following 6 symptoms: 
− Abdominal pain intensity 
− Nausea intensity 
− Fullness before finishing a meal intensity 


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 3  of 5 9  
C o nfi de nti al  
− 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  
2. 2  
Sec o n d ar y O bjecti ves  – Sec o n d ar y E n d p oi nts  
T he sec o n dar y o bjecti ves are t o c haracterize f urt her t he efficac y of A K 0 0 2 i n s u bjects wit h E G 
a n d/ or 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 s u bjects ac hie vi n g mea n  e osi n o p hil c o u nt ≤1 cell/h pf  i n 5 hi g hest gastric h pf 
a n d/ or 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 treat me nt res p o n ders at Wee k 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 s y m pt o m sc ore a n d mea n e osi n o p hil c o u nt ≤4 cells/ h pf i n 5 hi g hest 
gastric h pf a n d/ or 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 or ti o n of s u bjects 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 s u bjects 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  
2. 3  
E x pl or at or y O bjecti ves – E x pl or at or y E n d p oi nts 
T he e x pl orat or y o bjecti ves are t o e val uate t he effect of A K 0 0 2 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 ge fr o m baseli ne i n 
 o ver ti me  
•  
F or s ubject s wit h 
 
 Pr o p orti o n of s u bjects ac hie vi n g a 
 
 at Wee k 2 4 
•  
C ha n ge fr o m baseli ne i n 
 o ver ti me  
2. 4  
S afet y O bjecti ves  – S afet y E n d p oi nts  
T he safet y o bjecti ve of t he st u d y is t o e val uate t he st u d y dr u g safet y pr ofile usi n g t he f oll o wi n g 
safet y e n d p oi nts:  
C CI
C CI
C CI
C CI
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Statistical Analysis Plan – Version 1 
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Allakos Inc. 
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• 
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  
• 
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 moderate-to-severe EG and/or EoD 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 study.  
Subjects who have signed the informed consent form (ICF) will be screened within 35 days prior 
to Study Day 1.  
The study will be carried out as follows: 
• 
An 18 to 45-day screening period with baseline evaluations, including active symptoms of 
disease (gathered by PRO questionnaire) and EGD with biopsy.  
• 
Prior EGD may be used for eligibility as long as it was collected within 30 days of the first 
screening visit for the AK002-016 study and was performed and centrally evaluated for the 
AK002-016 study. 
• 
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) and whether the subject has EG with or without EoD (EG ± EoD) 
or EoD without EG. The interactive response technology (IRT) will randomly assign 
subjects 1:1 to receive AK002 or placebo. 


 
Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
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• 
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 due to 
unforeseen medical circumstances where it is deemed to be medically necessary to treat an 
unrelated medical condition or when given as a premedication prior to infusion or to treat 
an IRR that occurs during infusion (see Section 6.3 and Protocol Section 8.1). 
• 
Eligible subjects will receive the first dose of placebo or AK002 (1 mg/kg) on Day 1, with 
premedication of 60 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.  
• 
During the Treatment period, subjects will return to the clinic for study visits as described 
in the Schedule of Events (Table 1). 
• 
Subjects will continue to complete daily PRO questionnaires throughout the study and the 
follow-up period. 
• 
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.  
• 
Follow-up will occur for 84 (±3) days after the last dose unless subjects decide to enter a 
long-term extension study. Follow-up visits for subjects opting not to enter the extension 
study will occur on Days 176 (±3), 197 (±3), and 225 (±3).  
• 
Subjects who satisfactorily complete through Day 176 of AK002-016 have the option to 
receive AK002 in a separate open-label extension study if all eligibility criteria for the 
extension study are satisfied. Subjects who enroll in the AK002-016X extension study prior 
to Day 197 occurring will not complete the Day 197 or Day 225 procedures under Protocol 
AK002-016.  
• 
Total study duration is approximately 35–37 weeks. For subjects entering the AK002-016X 
extension study, the total study duration is approximately 28–37 weeks. 
The overall schedule of procedures and assessments are presented in Table 1. 
 
 


Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n – Versi o n 1 
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 6  of 5 9  
C o nfi de nti al  
T a ble 1 
Sc he d ule of Assess me nts  
 
Scree ni n g  
( 1 8– 4 5 da ys)  
Tre at me 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  
 
 
D a y 8  
( ± 2 da ys) 
 
D a y 1 5  
( ± 2 da ys) 
 
D ose 2  
D a y 2 9  
( ± 3 da ys) 
D ose 3  
D a y 5 7  
( ± 3 da ys) 
D ose 4  
D a y 8 5  
( ± 3 da ys) 
D ose 5  
D a y 1 1 3  
( ± 3 da ys) 
D ose 6  
D a y 1 4 1  
( ± 3 da ys) 
D a y 1 6 9  
( ± 3 da ys) or 
2 8 da ys 
after last 
d ose if E T  
D a y 1 7 6  
( ± 3 da ys) or 
3 5 da ys 
after last 
d ose if E T 2 9 
D a y 1 9 7  
( ± 3 da ys) or 
5 6  da ys 
after last 
d ose if E T 2 9 
D a y 2 2 5  
( ± 3 da ys) or 
8 4  da ys 
after last 
d ose if E T 2 9 
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p hics  
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Me dical Hist or y  
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Pri or/ C o nc o mita nt Me dicati o ns  
X 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
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 
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 
Baseli ne Diet Assess me nt 7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseli ne Diet C o m plia nce 8 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
St o ol f or O va a n d Parasite 9 
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 ( ma y 
i ncl u de A d diti o nal Q uesti o ns)1 1 
< ------------------------------------------------------------------C o m plete electr o nicall y o ne 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, a n d St u d y Da y 2 8 ----------------------------------------> 
 
< ---------------------------------------------------C o m plete electr o nicall y o n St u d y Da y 7 a n d St u d y Da y 2 8 -----------------------------------------------------> 
E G D wit h Bi o ps y 1 2, 1 4 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Bl o o d f or Scree ni n g C he mistr y 
(i ncl u des h C G a n d F S H) 1 2, 1 5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI
C CI
C CI


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Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
Page 17 of 59 
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Table 1 
Schedule of Assessments cont. 
 
Screening 
(18–45 days) 
Treatment Period 
(20 weeks) 
Follow-Up Period30 
(12 weeks) 
Baseline1 
Prior 
to 
Day 1 
Dose 1 
Day 1 
 
 
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  
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 ET29 
Blood for Serology and 
Strongyloides stercoralis 12,16 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for Total Serum IgE12,17 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Previous Treatments Review 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Access IRT: Stratification and 
Randomization18 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Access IRT: IP Kit Assignment 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Premedication: Prednisone19 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration20 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Blood for CBC with 
differential12,21 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Chemistry12,22 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for PK12,23 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for ADA12,24 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine for Urinalysis12,25 
X 
 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Dipstick Pregnancy Test26 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Non-serious Adverse Events27 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious Adverse Events28 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Begin AK002-016X extension 
study at least 1 day after 
Day 176 Visit (if applicable)31 
 
 
 
 
 
 
 
 
 
 
 
X33 
X33 
X33 
Blood for histamine/tryptase32 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 


Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n – Versi o n 1 
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 8  of 5 9  
C o nfi de nti al  
T a ble 1 N otes  
A D A:  A nti -A K 0 0 2 a nti b o d y  
E T: 
Earl y Ter mi nati o n  
I R T: 
I nteracti ve Res p o nse Tec h n ol o g y 
C B C:  C o m plete bl o o d c o u nt  
F S H:  F ollicle -sti m ulati n g h or m o ne 
  
E C G:  Electr ocar di o gra m  
h C G:  H u ma n C h ori o nic G o na d otr o pi n  
 
e P R O: electr o nic Patie nt Re p orte d O utc o me  
I P: 
I n vesti gati o nal Pr o d uct 
P K:  
P har mac o ki netics  
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 eria are met a n d at least 4 diar y e ntries ha ve bee n 
c o m plete d d uri n g t he t hir d wee k of scree ni n g.  
2)  
At scree ni n g, hei g ht (i n c m) a n d wei g ht (i n k g) will be rec or de d. B o d y wei g ht will als o be meas ure d o n 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 after last 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  calc ulate t he a m o u nt of A K 0 0 2/ place 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 eac h i nf usi o n da y.  
3)  
Vital si g ns will be meas ure d at scree 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 last d ose if E T a n d o n all d os in g da ys: wit hi n 3 0 mi n utes pre d ose, 1 5 mi n utes 
( ± 5 mi n utes) after t he start of st u d y dr u g i nf usi o n, wit hi n 1 5 mi n utes 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 vital si g ns meas ure me nts ma y be 
c ollecte d at t he I n vesti gat or’s discreti o n if a n I R R occ urs. Vital si g ns i ncl u di n g s yst olic a n d diast olic bl o o d press ure, p ulse, b o d y te m perat ure, a n d res pirat or y rate will be 
meas ure d after t he patie nt has bee n at rest f or ≥5 mi n utes a n d bef ore a n y bl o o d dra ws ha ve bee n o btai ne d ( u nless c ol lecte d f or a n I R R). 
4)  
A 1 0 -lea d or 1 2-lea d E C G will be o btai ne d at scree ni n g bef ore a n y bl o o d is dra w n a n d after t he patie nt has bee n i n t he a p pr o priate p ositi o n for ≥5 mi n utes.  
5)  
A c o m plete p h ysical e xa mi nati o n will be perf or me d b y eit her t he I n vesti gat or or desi g nee a n d i ncl u de t he f oll o wi n g b o d y s yste m or or ga n assess me nts: s ki n; hea d, e yes, ears, 
n ose a n d t hr oat; t h yr oi d; l u n gs; car di o vasc ular; a b d o me n; e xtre mities; l y m p h n o des; a n d a brief ne ur ol o gical e xa mi nati o n.  
6)  
A s y m pt o m -directe d P E (i ncl u di n g  assess me nt of p ossi ble i nf usi o n site reacti o ns) will be perf or me d b y t he I n vesti gat or or desi g nee, as nee de d if a n y s y m pt o ms are re p orte d.  
7)  
A baseli ne diet assess me nt ( Pr ot oc ol A p pe n di x 3) will be perf or me d usi n g sta n dar dize d q uesti o ns. Eati n g patter ns,  f o o d a v oi da nce be ha vi ors, a n d c o nfir me d aller gies will be 
ca pt ure d. 
8)  
A baseli ne diet c o m plia nce c hec k will be perf or me d at e ver y st u d y visit, e xce pt as n ote d a b o ve, a n d a n y varia nces fr o m t he ba seli ne diet d oc u me nte d. Patie nts s h o ul d 
mai ntai n t he baseli ne diet t hr o u g h o ut t he st u d y.  
9)  
Fecal c ollecti o n kits f or O va a n d Parasite test will be pr o vi de d t o patie nts at scree ni n g. C ollecti o n kits s h o ul d be ret ur ne d  t o t he cli nical site wit hi n 1 da y of c ollecti o n. 
Ne gati ve res ults m ust be a vaila ble pri or t o ra n d o mizati 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 me a n d pass w or d. P R O q uesti o n naire s h o ul d be acti vate d f or a ll patie nts o n scree ni n g Da y 1. Patie nts wit h 
c o nc o mita nt hist or y of ast h ma or at o pic der matitis will recei ve a n e xt ra q uesti o n, a b o ut eac h, as a p pr o priate. All patie nts will recei ve d ys p ha gia q uesti o n d uri n g scree ni n g a n d 
will c o nti n ue t o recei ve t he q uesti o n after e nr oll me nt if wee kl y a vera ge d ys p ha gia is ≥3 d uri n g a n y 2 wee ks of scree ni n g.  
1 1)  P R O s h o ul d be c o m plete d ar o u n d t he sa me ti me eac h da y. Pri or t o e nr oll me nt, t he P R O wee kl y a vera ges of a b d o mi nal pai n, na usea, a n d diarr hea o ver t h e scree ni n g peri o d 
will be calc ulate d a n d use d t o assess eli gi bilit y. Wee kl y a vera ge T otal S y m pt o m Sc ore ( T S S 6) will be calc ulate d f or eli gi bilit y a n d stratificati o n. P R O wee kl y a vera ge f or 
d ys p ha gia will als o be assesse d pri or t o e nr oll me nt t o deter mi ne if t he patie nt s h o ul d c o nti n ue recei vi n g t he 1 -q uesti o n dail y d ys p ha gia q uesti o n.  
C CI
C CI


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Table 1 Notes cont. 
12) Specimen processed by central laboratory. See central laboratory manual for collection and processing details. 
13) 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 endoscopy (EGD) and biopsy assessments will be performed on Day 169 (±3) or 28 (±3) days after last 
dose of study drug if ET. If the Day 141 infusion occurs out of window, the EGD should occur 28 (±3) days from the date of Day 141. Post-treatment EGD 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 and whether patient is EoD-only will occur. Randomization and stratification will be conducted through the IRT system. 
19) Premedication with 60 mg oral prednisone or approved alternative is required 12–24 hours prior to first infusion. Premedication may be administered prior to subsequent 
infusions at the Investigator’s discretion, but only with written Medical Monitor approval. 
20) Study drug will be administered as a single peripheral IV infusion over at least 4 hours for Dose 1 and at least 3 hours for Dose 2. Doses 3–6 should occur over at least 
2 hours, depending on prior infusion tolerability. Please refer to the Pharmacy Manual. 
21) Blood for CBC with differential, including absolute blood eosinophil count, will be obtained just prior to each infusion, 1 hour (±15 minutes) after the end of each infusion as 
well as during the screening period, and on Days (±3) 8, 15, 169, 176, 197, and 225 or 35, 56, and 84 (±3) days after last dose if ET. All differential blood counts from Day 1 
(post-dose) 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 predose on dosing Days 1, 29, 57, 85, 113, and 141, as well as on 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. 
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 (±3), 35 (±3), 
56 (±3), and 84 (±3) days after last dose of study drug if ET. 
24) Blood for ADA will be collected 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 (±3), 35 (±3), 
56 (±3), and 84 (±3) days after last dose of study drug if ET. ADA sample will also be collected any time an immunogenicity-related AE occurs. 
25) Urine for standard urinalysis will be obtained predose on dosing Days 1, 29, 57, 85, 113, and 141 as well as during the screening period and on Day 176 and Day 197 or 
35 (±3) days and 56 (±3) days after last dose of study drug if ET. 
26) A small amount of urine collected for urinalysis will be used for dipstick pregnancy test on all infusion days and on Day 176 and 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. 


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Table 1 Notes cont. 
27) The capture of non-serious AE and adverse events of special interest will begin after the first dose of study drug has occurred. 
28) The reporting of SAE occurring after signing 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. 
29) Patients who sign the informed consent for the AK002-016X extension study will complete the procedures for Day 176 and may begin open-label dosing in the extension 
study, if eligible, one day after the completion of Day 176 visit. In this case, patients will not complete the Day 197 or Day 225 procedures under Protocol AK002-016. 
Open-label dosing and follow-up will occur under the AK002-016X extension study. Patients who choose to enter the AK002-016X extension study after Day 197 but before 
Day 225 will not complete Day 225 procedures.  
30) The ET visits should be conducted 28 (±3), 35 (±3), 56 (±3), and 84 (±3) days after the 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 and end-of-study blood work may occur on the same day (28 days after last dose and 35 days after last dose visit procedures). If the 
end-of-study visit occurs more than 35 days after the 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. 
31) The final hematology assessment for AK002-016 must be collected prior to the subject taking prednisone premedication for AK002-016X. Therefore, dosing in 
AK002-016X must take place at least 1 day after completion of the Day 176 visit for AK002-016. Subjects may start AK002-016X dosing 1 day after completion of the 
Day 176 Visit. 
32)  Blood samples for histamine and tryptase to be collected within 1–2 hours of start of symptoms if there is any suspicion of anaphylaxis. 
33)  For patients who do not start the extension study before Day 197 or Day 225, visit procedures will occur as per the AK002-016 study. 
 


 
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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 dose group of 1 mg/kg 
AK002 followed by 5 doses of 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 
• 
Screening phase: 18–45 days prior to study drug administration 
• 
Treatment phase: 20 weeks  
• 
Follow-up period: 84 days (±3) following the last dose of study drug  
3.2.3 
Methods of Assigning Subjects to Treatment Group 
Approximately 160 subjects with symptomatic EG and/or EoD will be stratified by baseline TSS 
and disease status (EG ± EoD, EoD). Subject will be randomized 1:1 to receive 1 of 2 dose 
regimens using stratified randomized blocks in a double-blind manner.  
• 
AK002 at 1 mg/kg for the first dose followed by 3 mg/kg administered every 4 weeks for 
5 subsequent doses. 
• 
6 doses of placebo 
It is anticipated that at least 90 subjects with EG ± EoD will be enrolled, and up to 70 subjects 
with EoD without EG will be enrolled. 
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 with regard to 
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. 
3.5 
Determination of Sample Size 
A total of approximately 160 subjects will be enrolled.  


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 2  of 5 9  
C o nfi de nti al  
First C o -Pri m ar y E n d p oi nt:  A sa m ple size of 8 0 s u bjects per treat me nt gr o u p will ha ve > 9 9 % 
p o wer t o de m o nstrate a greater pr o p orti o n of tiss ue res p o n ders at Wee k 2 4 i n A K 0 0 2 s u bjects 
w he n c o m pare d t o place b o s u bjects, ass u mi n g t he pr o p orti o ns of res p o n ders are 0. 6 a n d 0. 1 i n 
A K 0 0 2 a n d place b o gr o u ps, res pecti vel y.  
Sec o n d C o -Pri m ar y E n d p oi nt:  A sa m ple size of 8 0 s u bjects per gr o u p will pr o vi de 9 6 % p o wer 
t o detect a statisticall y si g nifica nt differe nce of 7. 4 p oi nts bet wee n A K 0 0 2 a n d place b o i n t he 
mea n re d ucti o n fr o m baseli ne i n T S S at Wee ks 2 3 – 2 4, ass u mi n g a c o m m o n sta n dar d de viati o n 
of 1 2. 5 p oi nts a n d a p o p ulati o n mea n baseli ne T S S of 3 0 p oi nts.  
4.  
Defi niti o ns  
4. 1  
Ter mi n ol o g y a n d Defi niti o ns  
T a ble 2 
Ter mi n ol o g y a n d Defi niti o n s 
 
Ter mi n ol o g y  
Defi niti o n  
“ A n d/ Or” 
C o n diti o n A “a n d/ or” B is Tr ue w he n  
•  A is Tr ue a n d B is n ot e val ua ble ( n ot a p plica ble)  
•  B is Tr ue a n d A is n ot e val ua ble ( n ot a p plica ble)  
•  A is Tr ue a n d B is Tr ue w he n b ot h A a n d B are e val ua ble  
Baseli ne  
Baseli ne f or n o n -dail y assess me nt (e . g., la b orat or y tests a n d  
) is defi ne d as t he 
n o n -missi n g val ue c ollecte d m ost rece nt t o a n d bef ore t he ti me of t he ver y first d ose 
of st u d y dr u g. T his i ncl u des la b test c ollecte d o n Da y 1 Pre d ose as a n e xa m ple. 
Baseli ne T otal S y m pt o m Sc ore ( T S S) will be  t he a vera ge of t he wee kl y  T S S 
c ollecte d i n t he last 2  wee ks pri or t o t he first d ose .  
C o m pleter f or t he St u d y  
S u bject s w h o c o m plete at least t hr o u g h t he Da y 1 7 6 visit if c o nti n ui n g t o t he 
A K 0 0 2 -0 1 6 X st u d y or Da y 2 2 5 visit if n ot c o nti n ui n g t o t he A K 0 0 2 -0 1 6 X st u d y . 
C o nc o mita nt Me dicati o n  
Me dicati o n c ollecte d o n t he Pri or/ C o nc o mita nt Me dicati o n C R F, wit h e n d date 
o n/after St u d y Da y 1. N ote a Pri or Me dicati o n ma y als o be a C o nc o mita nt 
Me dicati o n if t he start date is pri or t o St u d y Da y 1 a n d e n d date is o n/after St u d y 
Da y  1.   
E nr olle d  
S u bject  w h o is ra n d o mize d t o a treat me nt gr o u p.  
Ne wl y I nitiate d Me dicati o n  Ne wl y i nitiate d me dicati o n refers t o a n y me dicati o n wit h  a start date ≥ St u d y Da y  1  
Patie nt -Re p orte d O utc o me  
T he patie nt -re p orte d o utc o me (P R O ) q uesti o n naire e val uates 8 differe nt s y m pt o ms 
wit h 1 0 dail y q uesti o ns f or i nte nsit y a n d fre q ue nc y:  
•  A b d o mi nal pai n i nte nsit y  
•  Na usea i nte nsit y  
•  V o miti n g i nte nsit y  
•  V o miti n g fre q ue nc y  
C CI


 
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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 Disease Status 
(2 levels; EG ± EoD, EoD) 
For EG with/without EoD subjects: Mean eosinophil count ≤4 cells/hpf in 5 highest 
gastric hpf and/or mean eosinophil count ≤15 cells/hpf in 3 highest duodenal hpf. 
For EoD subjects: Mean 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 
≤4 cells/hpf in 5 highest gastric hpf and/or mean eosinophil count ≤15 cells/hpf in 
3 highest duodenal hpf. 
4.2 
Target of Estimation 
The estimand (target of estimation) for Protocol AK002-016 is: 
 
In subjects with EG and/or EoD, what is between group (AK002 vs. Placebo) difference in 
the proportion of tissue eosinophil responders at Week 24, and group difference in TSS 
change from baseline to Weeks 23–24 as measured by the patient-reported outcome (PRO) 
questionnaire.  


 
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The sections below describe the attributes of the estimand consistent with the ICH E9 (R1) 
Addendum (FDA, 2021). 
4.2.1 
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. Subjects must have a histological diagnosis of EG and/or 
EoD, as well as moderately to severely active symptomatic disease. 
A key aspect of eligibility is that subjects must complete at least 4 daily PRO questionnaires per 
week for a minimum of 3 weeks during the screening period. In addition, 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. 
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. 
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. An appropriate method for handling missing data through statistical 
modeling (e.g., multiple imputation [MI]) will be used (Sections 5.4.1, 5.4.2, and 6.11). The 
estimand will provide an answer to the question that is crucial to individual subjects: 


 
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“If I take this study drug 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. 
5. 
Statistical Methods 
5.1 
General Methodology  
All statistical analyses will be conducted using SAS v9.4 or later version on the Microsoft 
Windows Operating System.  
All 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.  


 
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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.  
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. 


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 7  of 5 9  
C o nfi de nti al  
T a ble  3  
A n al ysis Wi n d o w R ules f or 
 
 
T a ble 4  
A n al ysis Wi n d o w R ules f or Vit al Si g n a n d L a b or at or y Test s 
Visit Descri pti o n  
Wi n d o w  
Baseli ne  
O n or Pri or t o Da y 1  Pre d ose  
Da y 1  
Pre d ose o n i nf usi o n Da y 1  
Da y 2 9  
Da y 1 P ost d ose t o Da y 4 2  
Da y 5 7  
Da y 4 3  t o Da y 7 0  
Da y 8 5  
Da y 7 1  t o Da y 9 8  
Da y 1 1 3  
Da y 9 9 t o Da y 1 2 6 
Da y 1 4 1  
Da y 1 2 7 t o Da y 1 58 
Da y 1 7 6  
Da y 1 5 9  t o Da y 1 8 6  
Da y 1 9 7  
Da y 1 8 7 t o E n d of St u d y  
Visit Descri pti o n  
Wi n d o w  
Baseli ne  
O n or Pri or t o Da y 1 Pre d ose  
Da y 1  
Da y 1 P ost d ose  
Da y 1 5  
Da y 2 t o Da y 2 2 
Da y 2 9  
Da y 2 3 t o Da y 4 2  
Da y 5 7  
Da y 4 3 t o Da y 7 0  
Da y 8 5  
Da y 7 1 t o Da y 9 8  
Da y 1 1 3  
Da y 9 9 t o Da y 1 2 6  
Da y 1 4 1  
Da y 1 2 7 t o Da y 1 5 8  
Da y 1 7 6  
Da y 1 5 9 t o 1 8 6  
Da y 1 9 7  
Da y 1 8 7 t o E n d of St u d y  
C CI


 
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Table 5 
Analysis Window Rules for PK Concentration and ADA 
 
Table 6 
Analysis Window Rules for Blood Histamine and Urinalysis 
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. 
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  
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 


 
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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 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. 
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 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, and disease stratum 
(EG ± EoD vs. EoD without EG) 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 ; 
 
class DISEASE_STRAT ; 
 
mcmc chain=multiple impute=full initial=em nbiter=200 niter=100 ; 
var B_EOS DISEASE_STRAT (3 levels) B_TSS TSS_W01_02 TSS_W03_04  
... TSS_W21_22 TSS_W23_24 ; 
run ;  


 
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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 
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 
There will be 2 database locks for this study: 
• 
A provisional database lock after all subjects complete the Day 169 visit to allow for the 
analysis of safety and efficacy data through Day 169. 
• 
A final database lock after all subjects complete the study to allow for the analysis of any 
safety data collected after Day 169.  


 
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For each 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 provisional database lock is complete. After the provisional 
database lock, the randomization code will be made available to a restricted number of 
individuals at Allakos who are involved in the data analysis. Data analysis will commence after 
the provisional data lock and the final database lock, respectively. In addition, the PK and ADA 
data may be locked and assessed separately. 
5.7 
Multicenter Study 
Analysis will be performed pooling data across study sites. 
The study will have approximately 60 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 
pooled analysis center for the assessment of site effects. Sites from the following geographic 
clusters have been identified for pooling data across study sites: 
• 
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 


 
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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: 
• 
Baseline TSS (<28, ≥28) 
• 
Disease strata (EG ± EoD, EoD)  
• 
Gender (Male, Female) 
• 
Age (<65, ≥65) 
• 
Race (White, Non-White) 
6. 
Statistical Analysis 
6.1 
Analysis Populations 
The population of “all screened subjects” comprises subjects who signed the informed consent 
(ICF). 


 
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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 MITT population 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 MITT population is the primary analysis population for all efficacy and safety analyses. 
Analysis using the ITT population will be carried out if ≥5 randomized subjects do not receive 
study drug. The PP population will be used to evaluate robustness for the primary endpoints and 
select secondary endpoints when appropriate.  
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 


 
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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.  
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 MITT and PP populations. 
6.5 
Baseline Disease Characteristics 
Baseline disease characteristics including demographics, weight, blood eosinophils 
(≥500 cells/µL), IgE, history of atopic dermatitis, functional GI symptoms, history of EG and/or 
EoD, gastric eosinophils (per 5 hpf in subject with EG), duodenal eosinophils (per 3hpf in EoD), 
TSS total score at baseline, TSS (<28 vs. ≥28), PRO symptom scores, and baseline elevated 
esophagitis 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). 


 
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6.7 
Electrocardiogram 
A listing of electrocardiograms (ECG) overall interpretation at screening visit will be provided. 
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.  


 
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Medications will be tabulated separately based on the Safety population. The number (n and %) 
of subjects taking at least 1 medication and the number (%) of subjects taking each medication at 
the preferred term level will be tabulated by ATC4, and PT. Subjects taking the same PT 
medication twice will only be counted once. 
A subject data listing will be provided to include the reported medication name, the WHODD 
PT, ATC4, study day and pertinent subject information. 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 factors (baseline TSS [<28 vs. ≥28] and Disease Strata 
[EG ± EoD vs. EoD]) 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*DISEASE_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 by ANCOVA (primary analysis) 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) and disease strata (EG ± EoD, EoD) 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.  
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. From this imputed data set, the biweekly TSS is set to 
missing if it is derived from the daily scores containing ≥4 daily scores collected on/after the 
ICE. This setting creates the monotone missing data set.  
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 


 
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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. 
 
proc mi seed=135791 nimpute=10;  
 
class TRTMT; 
 
var B_EOS DISEASE_STRAT B_TSS TSS_W01_02 TSS_W03_04 ... 
 
TSS_W21_22  
 
 
TSS_W23_24; 
 
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 ; 
The second sensitivity analysis is based on the tipping point method. In this method, the missing 
biweekly TSS will be imputed with different adjustments for the active treatment subjects and 
placebo subjects under the MNAR assumption in which the search for a tipping point reverses 
the study conclusion (i.e., p-value no longer <0.05 for the treatment effect). A shift ranging from 
-x to +y representing different levels of improvement or worsening due to ICE will be added to 
the imputed TSS. An example of the SAS code is as follows. 
 
proc mi seed=579864 nimpute=10; 
 
class DISEASE_STRAT TRTMT; 
 
var B_EOS DISEASE_STRAT B_TSS TSS_W01_02 TSS_W03_04 ...  
 
 
TSS_W21_22 TSS_W23_24; 
 
monotone reg; 
 
mnar  adjust(TSS_W01_02 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
adjust(TSS_W03_04 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
. . . 
 
 
adjust(TSS_W21_22 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
adjust(TSS_W23_24 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
adjust(TSS_W01_02 / adjustobs=(TRTMT='0') shift=&d0.)  
 
 
adjust(TSS_W03_04 / adjustobs=(TRTMT='0') shift=&d0.)  
 
 
. . . 
 
 
adjust(TSS_W21_22 / adjustobs=(TRTMT='0') shift=&d0.)  
 
 
adjust(TSS_W23_24 / adjustobs=(TRTMT='0') shift=&d0.); 
run; 
Note, a positive adjustment (shift>0) will increase (worsen) TSS and a negative adjustment 
(shift<0) will reduce (improve) TSS. Varying shift parameter from 0 (minimum) to maximum, 
where maximum shift parameter will be guided by the mean difference between subjects that 
drop out after the tth visit and subjects that continue. This sensitivity analysis will vary the shift 
parameter independently between the active treatment subjects and placebo subjects.  


 
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After the data are imputed, the ANCOVA with the synthesizing method will be applied using 
methods described in Section 5.4.2. 
P-values for the between treatment comparison from the synthesized ANCOVA results will be 
plotted against the shift parameters to demonstrate the robustness of the study conclusion against 
the various imputation strategies to account for the ICE effect. 
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 ANCOVA 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 gastric or duodenal only 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). For subjects who provide both gastric and duodenal biopsies, the calculation will be 
based on the average count of the highest readings from the Day 169 biopsy that corresponds in 
location (gastric or duodenal) to the location with the highest average count at baseline. 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, and disease status 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 Gastric and/or 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). 
6.12.3 
Proportion of Treatment Responders  
Treatment responder is defined as >30% improvement in TSS and mean eosinophil count 
≤4 cells/hpf in 5 highest gastric hpf and/or 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.  


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 0  of 5 9  
C o nfi de nti al  
6. 1 2. 4  Pr o p orti o n of S u bject s wit h ≥5 0 % Re 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  
T hese 2 e n d p oi nts will be a nal yze d usi n g t he C M H test stratifie d b y t he ra n d o mizati o n 
stratificati o n fact ors.  
6. 1 2. 5  C h a n ge i n W ee kl y T S S O ver Ti me  
Pri or t o t he a nal ysis, t he missi n g wee kl y T S S sc ores will be i m p ute d si milarl y t o  t he i m p utati o n 
f or t he missi n g bi wee kl y P R O T S S sc ores ( Secti o n  5. 4. 2 ). T he i m p ute d data sets will be 
a nal yze d usi n g t he mi xe d m o del f or re peat meas ures ( 
) wit h treat me nt, wee k, a n d 
treat me nt- b y-wee k i nteracti o n as fi xe d fact ors, baseli ne P R O T S S (c o nti n u o us), a n d E o D 
wit h o ut E G  (Y/ N ) as c o variates, a n d s u bject as re peate d meas ure u nit o ver ti me. T he m o del will 
use c ha n ge fr o m baseli ne i n t he wee kl y T S S fr o m Wee k s 1 t hr o u g h Wee k 2 4.  
T he m o del varia nce -c o varia nce matri x will be u nstr uct ure d.  If t he c o m p utati o n d oes n ot 
c o n ver ge, t he c o varia nce 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 i m pr o ve d Ke n war d- R o d ger’s met h o d ( S A S K R 2  o pti o n) will be 
use d t o deri ve t he de n o mi nat or de grees- of -free d o m. T he L S M a n d 9 5 % CI  f or t he bet wee n gr o u p 
differe nce will be esti mate d usi n g t he si m ple c o ntrast at eac h wee k.  
A sa m ple S A S c o de is pr o vi de d as f oll o ws. 
 
p r o c  m i x e d  d a t a = A D E F  m e t h o d = R E M L  ;  
 
c l a s s  T R T P N  U S U B J I D  W E E K  ;  
 
m o d e l  C H G  =  B _ T S S  D I S E A S E _ S T R A T  T R T P N  W E E K  T R T P N * W E E K  /  d d f m = K R 2  ;   
 
r e p e a t e d  W E E K  /  s u b j e c t = U S U B J I D ( T R T P N )  t y p e = U N  ;  
 
l s m e a n s  T R T P N * W E E K  /  p d i f f  c l  ;   
r u n  ;  
T he rati o nale f or usi n g t he  
 m o del is t hat t his a nal ysis is a p pr o priate ass u mi n g s u bjects 
wit h missi n g data be ha ve si milarl y t o ot her s u bjects i n t he sa me treat me nt gr o u p. Ha vi n g 
i ncl u de d i n t he m o del baseli ne s y m pt o m score ( T S S), disease stat us (E G ± E o D  vs. E o D ), a n d 
res p o nse traject or y pri or t o missi n g, it is reas o na bl y t o belie ve t hat t he missi n g data are eit her 
c o m pletel y at ra n d o m ( M C A R) or at ra n d o m ( M A R) i n t his setti n g . I n a n ot her w or ds, if missi n g 
mec ha nis m is n ot M C A R, it is li kel y e x plai na ble b y t he a b o ve m o del c o v ariates a n d res p o nse 
traject or y. A sa m ple S A S c o de is i ncl u de d i n A p pe n di x 4 . 
6. 1 3  
A n al ysis of E x pl or at or y E n d p oi nts 
6. 1 3. 1  C h a n ge i n 
 
C ha n ge fr o m b aseli ne i n t he 
 
 
C CI
C CI
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 1  of 5 9  
C o nfi de nti al  
 T his a nal ysis met h o d is si milar t o t he 
a nal ysis f or t he sec o n d c o -pri mar y e n d p oi nt ( S ecti o n 6. 1 1. 2 ). 
6. 1 3. 2  C h a n ge i n 
 
C ha n ge fr o m b aseli ne i n 
 s u m mar y (i ncl u di n g d o mai n scores) will be a nal yze d usi n g 
 
 
 si milar t o S ecti o n 6. 1 2. 5 . 
6. 1 3. 3  S u bjects  Ac hie vi n g 
 
at Wee k  2 4 
F or s u bjects wit h 
 
 at baseli ne , t he pr o p orti o n of s u bjects ac hie vi n g 
 
 at Wee k 2 4 will be a nal yze d usi n g t he 
 si milar t o 
Secti o n  6. 1 1. 1 . 
6. 1 3. 4  C h a n ge i n 
 
C ha n ge fr o m baseli ne i n 
 
si milar t o Secti o n 6. 1 2. 5  wit h 
 
 
 
6. 1 3. 5  
  
C ha n ge fr o m baseli ne i n 
 as 
descri be d i n  Secti o n 6. 1 2. 5 . T he m o del will i ncl u de 
 
 
 
 
•  
 
•  
 
•  
 
•  
 
•  
  
•  
 
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
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 2  of 5 9  
C o nfi de nti al  
•  
 
 
 
 
•  
 
 
 
  
6. 1 3. 6  
 
Met h o d s f or 
 a n d 
 are descri be d i n a se parate a nal ysis pla n. 
6. 1 4  
A n al ysis of P h ar m ac o ki netic E n d p oi nt  
T he a nal ysis of t he P K c o nce ntrati o n will be base d o n t he Safet y p o p ulati o n. A K 0 0 2 
c o nce ntrati o ns will be liste d b y treat me nt, s u bject, n o mi nal ti me, a n d act ual ti me. C o nce ntrati o ns 
t hat are bel o w li mit of q ua ntificati o n ( B L O Q) will be i n dicate d i n t he listi n g.  
Plas ma c o nce ntrati o ns will be s u m marize d at eac h n o mi nal ti me p oi nt se paratel y f or eac h 
treat me nt. T he f oll o wi n g descri pti ve statistics will be prese nte d: n, arit h metic mea n, S D, 
ge o metric mea n, % C V,  me dia n, mi ni m u m , a n d ma xi m u m .  
I n di vi d ual plas ma c o nce ntrati o n vs. act ual ti mes will be pl otte d f or eac h s u bject i n li near a n d 
se mi-l o garit h mic scales, place d o n t he sa me pa ge. Mea n plas ma c o nce ntrati o n at t he sc he d ule d 
ti me p oi nts will be pl otte d f or eac h treat me nt i n li near a n d se mi-l o garit h mic scale, wit h t he 
ass ociate d sta n dar d err ors (f or li near scale o nl y) at eac h sc he d u le d ti me p oi nt. 
I n t he pl ot, c o nce ntrati o ns t hat are B L O Q will be assi g ne d a val ue of 0 if t he y are c ollecte d 
pre d ose or assi g ne d a val ue of 1/ 2  t he l o wer li mit of q ua ntificati o n ( L L O Q) if t he y are c ollecte d 
p ost d ose.  
A nal ysis of P K para meters are s pecifie d se paratel y i n a P K a nal ysis pla n.  
6. 1 5  
S afet y A n al yses 
6. 1 5. 1  A d verse E ve nts  
Safet y assess me nts will be base d mai nl y o n t he nat ure, fre q ue nc y, relati o ns hi p, a n d se verit y of 
a d verse e ve nts ( A E) . T he A E will be c o de d b y pri mar y S O C a n d P T acc or di n g t o Me d D R A 
( versi o n 2 1. 0). T he treat me nt-e mer ge nt a d verse e ve nts ( T E A E) will be  s u m marize d b y t he 
n u m ber a n d perce nta ge ( n a n d %) of s u bjects i n eac h S O C a n d P T.  
C CI
C CI
C CI
C CI
C CI


 
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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.  
• 
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).  


 
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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. 
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 


 
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of the data recorded on the eCRF directly from source documents at the investigative site. The 
DM vendor will be responsible for performing edit checks and reviewing all data entered into the 
electronic database to identify discrepant and/or inconsistent values and to send queries to the 
clinical sites. The Investigator will be responsible for answering queries about discrepant data 
and providing electronic signatures to confirm data integrity.  
The programming of tables, listings and figures (TLF) based on the clinical data is outsourced. 
Allakos seeks to ensure the quality of the reports provided by the CRO in the form of TLF 
passing a rigorous validation process as follows:  
• 
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.  


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 1  of 5 9  
C o nfi de nti al  
9. 3  
A p pe n di x 3: List of T a bles, Fi g ures , a n d Listi n gs   
T a bles  
Ta ble 1 4. 1. 1a  
S u bject Dis p ositi o n a n d Reas o n f or Disc o nti n uati o n ( All Scree ne d S u bject s) 
Ta ble 1 4. 1. 1 b   
S u bject Dis p ositi o n a n d Reas o n f or Disc o nti n uati o n 
( Safet y/ MI T T P o p ulati o n) 
Ta ble 1 4. 1. 1c  
S u bject Dis p ositi o n a n d Reas o n f or Disc o nti n uati o n 
( Per Pr ot oc ol  P o p ulati o n) 
Ta ble 1 4. 1. 2  
Maj or Pr ot oc ol De viati o ns D uri n g t he St u d y: S u bject C o u nt 
( All Ra n d o mize d S u bjects)  
Ta ble 1 4. 1. 3  
A nal ysis P o p ulati o n: S u bject C o u nt ( All Ra n d o mize d S u bjects)  
Ta ble 1 4. 1. 4  
Per Pr ot oc ol P o p ulati o n E xcl usi o n ( All Ra n d o mize d S u bjects) 
Ta ble 1 4. 1. 5a 
De m o gra p hics a n d Baseli ne C haracteristics ( Safet y/ MI T T P o p ulati o n) 
Ta ble 1 4. 1. 5 b  
De m o gra p hics a n d Baseli ne C haracteristics ( Per Pr ot oc ol P o p ulati o n)  
Ta ble 1 4. 1. 6 
Me dical Hist or y b y S yste m Or ga n Class a n d Preferre d Ter m: S u bject 
I nci de nce ( Safet y P o p ulati o n) 
Ta ble 1 4. 1. 7. 1  
St u d y Dr u g E x p os ure ( Safet y P o p ulati o n) 
Ta ble 1 4. 1. 7. 2  
St u d y Dr u g E x p os ure ( Safet y P o p ulati o n) 
Ta ble 1 4. 1. 7. 3  
D urati o n of Treat me nt E x p os ure a n d C o m plia nce ( Safet y P o p ulati o n) 
Ta ble 1 4. 1. 8. 1 
Pri or Me dicati o ns b y A nat o mic T hera pe utic C he mical Classificati o n a n d 
Preferre d Ter m: S u bject I nci de nce ( Safet y P o p ulati o n)  
Ta ble 1 4. 1. 8. 2  
C o nc o mita nt Me dicati o ns b y A nat o mic T hera pe utic C he mical 
Classificati o n a n d Preferre d Ter m: S u bject I nci de nce ( Safet y P o p ulati o n)  
Ta ble 1 4. 1. 9 
Se verit y of C o nc o mita nt Ast h ma a n d At o pic Der matitis at Baseli ne 
( MI T T P o p ulati o n) 
Ta ble 1 4. 1. 1 0  
1 2- Lea d E C G E val uati o n at Baseli ne ( Safet y P o p ulati o n)  
Ta ble 1 4. 1. 1 1  
Baseli ne E osi n o p hil a n d 
 ( MI T T P o p ulati o n) 
Ta ble 1 4. 1. 1 2  
Baseli ne W orst D ys p ha gia Se verit y Sc ore ( MI T T P o p ulati o n) 
C CI


 
Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
Page 52 of 59 
Confidential 
Table 14.1.13 
Baseline Subject Reported Outcome Total and Symptom Scores 
(MITT Population) 
Table 14.1.14 
Baseline Vital Signs (MITT Population) 
Table 14.1.15 
Subject Incidence of Intercurrent Events (MITT Population) 
Table 14.2.1.1 
Tissue Eosinophil Responder at Week 24 – Primary and Sensitivity 
Analysis (MITT Population) 
Table 14.2.1.2.1 
Tissue Eosinophil Responder at Week 24 by Disease Subgroup 
(MITT Population) 
Table 14.2.1.2.2 
Tissue Eosinophil Responder at Week 24 by Gender (MITT Population) 
Table 14.2.1.2.3 
Tissue Eosinophil Responder at Week 24 by Age Subgroup 
(MITT Population) 
Table 14.2.1.2.4 
Tissue Eosinophil Responder at Week 24 by Baseline Peripheral Eosinophil 
Count Subgroup (MITT Population) 
Table 14.2.2.1 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – Primary Analysis – Multiple Imputation for Missing Weekly TSS 
(MITT 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 (MITT 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 Tipping Point Method 
(MITT Population) 
Table 14.2.2.4 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores – Multiple Imputation (Per Protocol Population) 
Table 14.2.2.5.1 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores by Disease Subgroup – Multiple Imputation (MITT Population) 
Table 14.2.2.5.2 
Change from Baseline in Average of Weeks 23-24 PRO Total Symptom 
Scores by Gender – Multiple Imputation (MITT Population) 


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 3  of 5 9  
C o nfi de nti al  
Ta ble 1 4. 2. 2. 5. 3 
C ha n ge fr o m Baseli ne i n A vera ge of Wee ks 2 3 - 2 4 P R O T otal S y m pt o m 
Sc ores b y A ge S u b gr o u p – M ulti ple I m p utati o n ( MI T T P o p ulati o n)  
Ta ble 1 4. 2. 2. 5. 4 
C ha n ge fr o m Baseli ne i n A vera ge of Wee ks 2 3 - 2 4 P R O T otal S y m pt o m 
Sc ores b y Baseli ne Peri p heral E osi n o p hil C o u nt S u b gr o u p – M ulti ple 
I m p utati o n ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 3  
C ha n ge fr o m Baseli ne t o Wee k 2 4 Tiss ue E osi n o p hil C o u nt 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 4 
S u bjects Ac hie vi n g Pea k Gastric a n d/ or D u o de nal I ntrae pit helial 
E osi n o p hils C o u nt ≤1 cell/ h pf  ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 5 
S u bjects Ac hie vi n g Tiss ue E osi n o p hil a n d T S S Treat me nt Res p o nse 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 6  
S u bjects wit h ≥5 0 % Re 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 
Ta ble 1 4. 2. 7  
C ha n ge fr o m Baseli ne i n Wee kl y T S S fr o m Wee k 1 T hr o u g h Wee k 2 4 
Usi n g M M R M  ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 8 
C ha n ge fr o m Baseli ne t o Wee k 2 4 Tiss ue 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 9. 1 
C ha n ge fr o m Baseli ne i n 
 – P h ysical C o m p o ne nt S u m mar y 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 9. 2 
C ha n ge fr o m Baseli ne i n 
 – Me ntal C o m p o ne nt S u m mar y 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 0  
S u bjects Ac hie vi n g Wee k 2 4 
 
 ( MI T T S u bjects wit h C o nc o mita nt E o E) 
Ta ble 1 4. 2. 1 1  
C ha n ge fr o m Baseli ne i n 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 1  
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 2  
C ha n ge fr o m Baseli ne i n Wee kl y 
 ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 3a  
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
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 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 4  of 5 9  
C o nfi de nti al  
Ta ble 1 4. 2. 1 2. 3 b  
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 4a 
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 4 b 
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 5 
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 6 
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 7 
C ha n ge fr o m Baseli n e i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 2. 8  
C ha n ge fr o m Baseli ne i n Wee kl y 
 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 3  
Se verit y of D ys p ha gia at Baseli ne a n d P ost- Baseli ne ( MI T T P o p ulati o n)  
Ta ble 1 4. 2. 1 4  
M or p h ol o gical Assess me nt of Gastric Bi o psies b y S y d ne y S yste m 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 5 
M or p h ol o gical Assess me nt of D u o de nal Bi o psies b y Mars h Scale 
Classificati o n ( MI T T P o p ulati o n)  
Ta ble 1 4. 2. 1 7  
C ha n ge fr o m Baseli ne i n B o d y Wei g ht ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 8 
T otal Ser u m I g E C o nce ntrati o n ( Per Pr ot oc ol P o p ulati o n)  
Ta ble 1 4. 2. 1 9  
S u bject I nci de nce of P ositi ve A nti- Dr u g ( A K 0 0 2) A nti b o d y ( A D A) Test 
( Safet y P o p ulati o n) 
Ta ble 1 4. 3. 1. 1 
O ver vie w of Treat me nt -E mer ge nt A d verse E ve nts ( Safet y P o p ulati o n)  
Ta ble 1 4. 3. 1. 2 
Treat me nt -E mer ge nt A d verse E ve nts b y Preferre d Ter m: S u bject I nci de nce 
( Safet y P o p ulati o n) 
Ta ble 1 4. 3. 1. 3 
Treat me nt -E mer ge nt A d verse E ve nts b y S yste m Or ga n Class a n d Preferre d 
Ter m: S u bject I nci de nce ( Safet y P o p ulati o n)  
C CI
C CI
C CI
C CI
C CI
C CI
C CI


 
Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
Page 55 of 59 
Confidential 
Table 14.3.1.4 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Maximum Severity: Subject Incidence (Safety Population) 
Table 14.3.1.5 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Relationship to Study Drug: Subject Incidence 
(Safety Population) 
Table 14.3.1.6 
Treatment-Emergent Adverse Events Leading to Study Drug 
Discontinuation by System Organ Class and Preferred Term: Subject 
Incidence (Safety Population) 
Table 14.3.1.7 
Treatment-Emergent Serious Adverse Events by System Organ Class and 
Preferred Term: Subject Incidence (Safety Population) 
Table 14.3.1.8 
Treatment-Emergent Adverse Events of Special Interest by System Organ 
Class and Preferred Term: Subject Incidence (Safety Population) 
Table 14.3.2.1 
Hematology: Change from Baseline by Visit (Safety Population) 
Table 14.3.2.2 
Blood Chemistry: Change from Baseline by Visit (Safety Population) 
Table 14.3.2.3 
Hematology: Shift from Baseline Classification by Visit (Safety Population) 
Table 14.3.2.4 
Blood Chemistry: Shift from Baseline Classification by Visit 
(Safety Population) 
Table 14.3.2.5 
Urinalysis: Change from Baseline by Visit (Safety Population) 
Table 14.3.3 
Summary of Vital Signs by Visit (Safety Population) 
 
Figures 
Figure 1 
Cumulative Distribution Function Plot of Change from Baseline in Average 
of Weeks 23-24 TSS 
Figure 2 
P-value from Between-Treatment Comparison in Weeks 23-24 TSS – 
Tipping Point Analysis 
 


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 6  of 5 9  
C o nfi de nti al  
Listi n gs  
Listi n g 1 6. 1. 7 
S u bject Ra n d o mizati o n Sc he d ule ( Ra n d o mize d P o p ulati o n)  
Listi n g 1 6. 2. 1. 1  
S u bjects Dis p ositi o n a n d Reas o n f or Dis p ositi o n ( Ra n d o mize d P o p ulati o n)  
Listi n g 1 6. 2. 1. 2  
S u bjects W h o ha d Maj or Pr ot oc ol De viati o ns ( Ra n d o mize d P o p ulati o n)  
Listi n g 1 6. 2. 1. 3  
S u bjects I ncl usi o n a n d t he Reas o n f or E xcl usi o n fr o m A nal ysis P o p ulati o ns 
( Ra n d o mize d P o p ulati o n) 
Listi n g 1 6. 2. 1. 4. 1 
De m o gra p hic a n d Baseli ne C haracteristics ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 1. 4. 2 
De m o gra p hic a n d Baseli ne C haracteristics – Hist or y of Disease 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 1. 5 
Me dical Hist or y ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 1. 6 
Die t Assess me nt ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 1. 7. 1  
Pri or Me dicati o ns ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 1. 7. 2  
C o nc o mita nt Me dicati o ns ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 1. 8  
I nterc urre nt E ve nts ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 1. 1  
Es o p ha g o- Gastr o - D u o de n osc o p y ( E G D) Bi o ps y Fi n di n g 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 1. 2  
D u o de nal bi o ps y assess me nts ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 1. 3 
Es o p ha geal bi o ps y assess me nts ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 2. 2a 
E osi n o p hilic Gastritis a n d Gastr oe nteritis Q uesti o n naire – Q uesti o n Te xt 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 2 b 
E osi n o p hilic Gastritis a n d Gastr oe nteritis Q uesti o n naire – Dail y Sc ore 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 2c 
E osi n o p hilic Gastritis a n d Gastr oe nteritis Q uesti o n naire – Wee kl y Sc ore 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 3 
E osi n o p hilic Gastritis E n d osc o pic Refere nce Sc ore ( E G E R S) 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 4a  
 Q uesti o n naire – Q uesti o n Te xt 
C CI


 
Pr ot oc ol A K 0 0 2 - 01 6  
Statistical A nal ysis Pla n  – Versi o n 1  
0 5 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 7  of 5 9  
C o nfi de nti al  
Listi n g 1 6. 2. 2. 4 b  
Q uesti o n naire – I n di vi d ual Q uesti o ns (I T T P o p ulati o n) 
Listi n g 1 6. 2. 2. 4c  
Q uesti o n naire – D o mai n Sc ores (I T T P o p ulati o n)  
Listi n g 1 6. 2. 2. 5a 
I nte nsit y of S y m pt o ms Q uesti o n naire – Q uesti o n Te xt ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 5 b 
I nte nsit y of S y m pt o ms Q uesti o n naire – I n di vi d ual Sc ores 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 1. 1  
All A d verse E ve nts ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 1. 2 
Seri o us A d verse E ve nts ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 3. 1. 3 
A d verse E ve nts wit h O utc o me of Deat h ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 3. 1. 4  
A d verse E ve nts Lea di n g t o St u d y Dr u g Disc o nti n uati o n ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 1. 5 
A d verse E ve nts of S pecial I nterest ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 3. 2. 1 
Cli nical La b orat or y Tests - He mat ol o g y ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 2. 2 
Cli nical La b orat or y Tests – Bl o o d C he mistr y ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 2. 3 
Cli nical La b orat or y Tests – Uri nal ysis ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 2. 4 
Cli nical La b orat or y Tests – Dia g n ostic I m m u n ol o g y/ M olec ular Bi ol o g y 
( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 2. 5 
Cli nical La b orat or y Tests – E n d ocri n ol o g y ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 2. 6 
Cli nical La b orat or y Tests – Parasit ol o g y ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 3. 2. 7 
Pre -I nf usi o n Bl o o d C ollecti o n ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 3. 1 
S u bsta nce Use – Alc o h ol C o ns u m pti o n at Scree ni n g ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 3. 2 
Uri ne Pre g na nc y Test ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 3. 4. 1  
St u d y Dr u g A d mi nistrati o n ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 4. 2  
St u d y Dr u g Acc o u nta bilit y ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 5 
Vital Si g ns ( Safet y P o p ulati o n)  
Listi n g 1 6. 2. 3. 6  
S u bject B o d y Size ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 3. 7. 1  
1 2- Lea d E C G I nter vals at Baseli ne ( Safet y P o p ulati o n)  
C CI


 
Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
Page 58 of 59 
Confidential 
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) 
 
 


 
Protocol AK002-016 
Statistical Analysis Plan – Version 1 
05 November 2021 
Allakos Inc. 
Page 59 of 59 
Confidential 
9.4 
Appendix 4: Example SAS Codes   
 
/** Multiple Imputation **/ 
proc mi data=TSS seed=1357986420 nimpute=50 out=TSS_IMPUTED1 ; 
       by TRTMT ; 
       class DISEASE_STRAT ; 
       mcmc chain=multiple impute=full initial=em nbiter=200 niter=100 ; 
var B_EOS DISEASE_STRAT 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 TRTMT; 
   model CHG=DISEASE_STRAT B_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;