Clinical trial NCT04322708
Conditions: Eosinophilic Esophagitis
Keywords: EoE Eosinophil Esophagitis
Sponsor: Allakos Inc.
Start date: 2020-07-06; Completion date: 2022-01-18
Enrollment: 277 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2/3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult and adolescent patients with active eosinophilic esophagitis. Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.

Detailed description:

Arms: arm 1: Subjects in this arm will receive 6 monthly doses of placebo. arm 2: Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) (1mg/kg). arm 3: 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: Placebo intervention 2: lirentelimab (AK002)
Intervention descriptions: intervention 1: Placebo intervention 2: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.

Protocol documents:
Prot_000.pdf: 
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of AK002 in Adult and Adolescent 
Subjects with Active Eosinophilic Esophagitis 
NCT Number: NCT04322708
Document Date: 28 Oct 2021
IRB Approval Date: 05 Nov 2021


975 Island Drive, Suite 201, Redwood City, CA 94065
Page 1 of 140 
Clinical Research Protocol AK002-014 
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of AK002 in Adult and Adolescent 
Subjects with Active Eosinophilic Esophagitis 
Protocol Number 
AK002-014 
Version and Date 
Original 
16 October 2019 
Amendment 1 
13 January 2020 
Amendment 2 
07 May 2020 
Amendment 3 
08 July 2020 
Amendment 4 
20 August 2020 
Amendment 5 
07 May 2021 
Amendment 6 2 October 2021 
Investigational Product 
AK002 
Study Phase 
2/3 
Sponsor 
Allakos Inc., 975 Island Drive, Suite 201, Redwood City, CA 
94065 USA 
Medical Monitor
Primary: 
 MD 
Telephone: 
Email: 
Backup: 
 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.  
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Protocol AK002-014 
Amendment 6 
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Allakos Inc. 
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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 subjects 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: 
AK002-014 
IND: 
143997 
Protocol Title: 
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of AK002 in Adult and 
Adolescent Subjects with Active Eosinophilic Esophagitis 
Original Protocol: 
16 October 2019 
Amendment 1: 
Amendment 2: 
Amendment 3: 
Amendment 4: 
Amendment 5: 
Amendment 6: 
13 January 2020 
07 May 2020  
08 July 2020  
20 August 2020 
07 May 2021 
28 October 2021 
Investigator Printed Name: 
Signature: 
Date: 


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
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Confidential 
Table of Contents 
Clinical Research Protocol AK002-014 ........................................................................................1 
Investigator Protocol Agreement..................................................................................................2 
Table of Contents ...........................................................................................................................3 
List of Tables .........................................................................................................................10 
List of Abbreviations .............................................................................................................11 
1.
Protocol Synopsis .................................................................................................................14 
2.
Background ..........................................................................................................................31 
2.1 
Siglec-8 and AK002 ..................................................................................................31 
2.2 
Overview of Nonclinical Studies ...............................................................................31 
2.3 
Overview of Clinical Studies .....................................................................................32 
2.4 
Eosinophilic Gastrointestinal Disorders ....................................................................34 
3.
Rationale for Study and Dose Selection .............................................................................36 
4.
Study Objectives ..................................................................................................................37 
4.1 
Primary Efficacy Objective .......................................................................................37 
4.2 
Secondary Objectives ................................................................................................37 
4.3 
Exploratory Objectives ..............................................................................................38 
4.4 
Safety Objectives .......................................................................................................38 
4.5 
Target of Estimation ..................................................................................................38 
4.5.1 
Population Targeted by the Scientific Question .........................................38 
4.5.2 
Variables of Interest (or Endpoint) Required to Address the 
Scientific Question ......................................................................................38 
4.5.3 
Treatment ....................................................................................................38 
4.5.4 
Intercurrent Events ......................................................................................39 
4.5.5 
Strategy for Handling Intercurrent Events ..................................................39 
4.5.6 
Summary Measure of the Estimand ............................................................39 


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5.
Study Design .........................................................................................................................39 
5.1 
Study Overview .........................................................................................................39 
5.2 
Schedule of Events ....................................................................................................42 
6.
Criteria for Evaluation ........................................................................................................47 
6.1 
Safety Endpoints ........................................................................................................47 
6.2 
Pharmacokinetic Endpoints .......................................................................................47 
6.3 
Efficacy Endpoints ....................................................................................................47 
6.3.1 
Co-Primary Efficacy Endpoints ..................................................................47 
6.3.2 
Secondary Efficacy Endpoints ....................................................................47 
6.4 
Exploratory Endpoints ...............................................................................................48 
7.
Subject Selection ..................................................................................................................48 
7.1 
Number of Subjects ...................................................................................................48 
7.2 
Study Population .......................................................................................................48 
7.3 
Inclusion Criteria .......................................................................................................49 
7.4 
Exclusion Criteria ......................................................................................................50 
8.
Prior and Concurrent Medications ....................................................................................52 
8.1 
Prohibited Medications ..............................................................................................52 
8.2 
Allowed Medications .................................................................................................53 
9.
Study Treatment ..................................................................................................................53 
9.1 
Formulation of Test Product and Placebo .................................................................53 
9.2 
Study Drug Packaging and Labeling .........................................................................54 
9.3 
Supply of Study Drug to the Investigational Site ......................................................54 
9.4 
Study Drug Dosage/Dosage Regimen .......................................................................54 
9.5 
Preparation of Study Drug .........................................................................................54 
9.6 
Study Drug Administration .......................................................................................55 


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
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Alla k os I nc.  
Pa ge 5 of 1 4 0  
C o nfi de nti al  
9. 7  
St u d y Dr u g St ora ge ................................................................................................... 5 6  
9. 8  
St u d y Dr u g Acc o u nta bilit y ........................................................................................ 5 6  
1 0.
S u bject N u m beri n g, Str atific ati o n, R a n d o miz ati o n, a n d Bli n di n g  ................................. 5 6 
1 0. 1  
S u bject N u m beri n g .................................................................................................... 5 6  
1 0. 2  
Stratificati o n a n d Ra n d o mizat i o n .............................................................................. 5 7 
1 0. 3  
Bli n di n g ..................................................................................................................... 5 8  
1 0. 4  
E mer ge nc y U n bli n di n g  .............................................................................................. 5 9 
1 1.
St u d y Pr oce d ures a n d G ui deli nes  ...................................................................................... 5 9 
1 1. 1  
Dietar y a n d Lif es t yle Restricti o ns ............................................................................. 6 0 
1 1. 2  
P har mac o d y na mic/ Efficac y -Relate d Pr oce d ures  ...................................................... 6 0 
1 1. 2. 1  
D ys p ha gia S y m pt o m Q uesti o n naire ............................................................ 6 0  
1 1. 2. 2  
S oli d F o o d Q uesti o n .................................................................................... 6 1  
1 1. 2. 3  
 
1 1. 2. 4  
 
1 1. 2. 5  
E G/ E o D P R O Q uesti o n naire ....................................................................... 6 1  
1 1. 2. 6  
......................................................... 6 2 
1 1. 2. 7  
Es o p ha g o- Gastr o - D u o de n osc o p y ................................................................ 6 2 
1 1. 2. 7. 1  E osi n o p hilic Es o p ha gitis Refere n ce Sc ore f or 
E n d osc o pic A b n or malities  ......................................................... 6 2 
1 1. 2. 7. 2  E G D Bi o ps y C ollecti o n .............................................................. 6 2  
1 1. 2. 8  
C o m plete Bl o o d C o u nt wit h Differe ntial .................................................... 6 3  
1 1. 2. 9  
Baseli ne Diet Assess me nt  ........................................................................... 6 4 
1 1. 2. 1 0  Baseli ne Diet C o m plia nce  ........................................................................... 6 4 
1 1. 3  
Safet y -Relate d Pr o ce d ur es  ......................................................................................... 6 5 
1 1. 3. 1  
C o nc o mita nt Me dicati o ns ........................................................................... 6 5  
1 1. 3. 2  
St o ol Sa m ple f or O va a n d Parasite  ............................................................. 6 5 
1 1. 3. 3  
B o d y Wei g ht a n d Hei g ht ............................................................................. 6 5  
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11.3.4 
Vital Signs ...................................................................................................66 
11.3.5 
Complete Physical Examination .................................................................66 
11.3.6 
Symptom-Directed Physical Examination ..................................................66 
11.3.7 
Electrocardiogram .......................................................................................66 
11.4 
Clinical Laboratory Measurements ...........................................................................67 
11.4.1 
Complete Blood Count with Differential ....................................................67 
11.4.2 
Blood Chemistry Profile .............................................................................67 
11.4.3 
Urinalysis ....................................................................................................68 
11.4.4 
Serum Pregnancy and Follicle-Stimulating Hormone ................................68 
11.4.5 
Serology ......................................................................................................68 
11.4.6 
Total Serum IgE ..........................................................................................69 
11.4.7 
Anti-Drug (AK002) Antibodies ..................................................................69 
11.4.8 
Pharmacokinetics ........................................................................................69 
11.4.9 
Blood for Exploratory Analysis ..................................................................69 
11.4.10 Blood for Exploratory Safety Analysis .......................................................69 
12.
Evaluations and Procedures by Visit .................................................................................70 
12.1 
Screening Period ........................................................................................................70 
12.2 
The Day Before the First Infusion .............................................................................71 
12.3 
Day 1 – Dose 1 ..........................................................................................................71 
12.4 
Day 8 (±1) ..................................................................................................................73 
12.5 
Day 15 (±2) ................................................................................................................73 
12.6 
Day 29 (±3) – Dose 2 ................................................................................................74 
12.7 
Day 57 (±3) – Dose 3 ................................................................................................75 
12.8 
Day 85 (±3) – Dose 4 ................................................................................................77 
12.9 
Day 113 (±3) – Dose 5 ..............................................................................................78 
12.10 Day 141 (±3) – Dose 6 ..............................................................................................80 


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12.11 Day 169 (±3) – Week 24 ...........................................................................................81 
12.12 Day 197 (±7) – End of Study ....................................................................................82 
12.13 Early Termination ......................................................................................................83 
12.14 Extended Follow-Up .................................................................................................83 
13.
Adverse Event Reporting and Documentation .................................................................84 
13.1 
Adverse Events ..........................................................................................................84 
13.2 
Serious Adverse Events .............................................................................................85 
13.3 
Adverse Events of Special Interest ............................................................................85 
13.4 
Infusion-Related Reactions .......................................................................................86 
13.5 
Anaphylaxis ...............................................................................................................87 
13.6 
Evaluating Adverse Events and Serious Adverse Events ..........................................87 
13.6.1 
Establishing Diagnosis ................................................................................87 
13.6.2 
Assessment of Intensity ..............................................................................87 
13.6.3 
Assessment of Causality to Study Drug ......................................................88 
13.6.4 
Assessment of Causality to Study Procedure ..............................................89 
13.6.5 
Action Taken ...............................................................................................89 
13.6.6 
Assessment of Outcome ..............................................................................89 
13.7 
Adverse Event Reporting Procedures ........................................................................90 
13.7.1 
All Adverse Events .....................................................................................90 
13.7.2 
Serious Adverse Event Reporting ...............................................................90 
13.7.3 
Pregnancy Reporting ...................................................................................91 
13.7.4 
Adverse Events of Special Interest Reporting ............................................92 
13.8 
Medical Monitoring ...................................................................................................92 
13.9 
Independent Data Monitoring Committee .................................................................93 
13.10 Study Withdrawal Criteria .........................................................................................93 
13.11 Study Stopping Rules ................................................................................................93 


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14.
Discontinuation and Replacement of Subjects ..................................................................94 
14.1 
Definition of Study Completion ................................................................................94 
14.2 
Early Discontinuation of Study Drug ........................................................................94 
15.
Statistical Methods ..............................................................................................................95 
15.1 
General Considerations .............................................................................................95 
15.2 
Sample Size ...............................................................................................................95 
15.3 
Data Sets Analyzed ....................................................................................................96 
15.4 
Subject Disposition ....................................................................................................96 
15.5 
Demographic and Baseline Characteristics ...............................................................96 
15.6 
Study Drug Exposure ................................................................................................96 
15.7 
Efficacy Analysis .......................................................................................................97 
15.7.1 
Primary Efficacy Endpoint Analysis ...........................................................97 
15.7.2 
Secondary Efficacy Endpoint Analysis .......................................................98 
15.7.3 
Exploratory Endpoint Analysis ...................................................................99 
15.8 
Safety Analysis ..........................................................................................................99 
15.9 
Subject Confidentiality ............................................................................................100 
16.
Data Collection, Retention, and Monitoring ...................................................................101 
16.1 
Data Collection Instruments ....................................................................................101 
16.2 
Data Management Procedures .................................................................................101 
16.3 
Data Quality Control and Reporting ........................................................................101 
16.4 
Database Lock/Disclosure of Randomization Code ................................................101 
16.5 
Archiving of Data ....................................................................................................102 
16.6 
Availability and Retention of Investigational Records ...........................................102 
16.7 
Monitoring ...............................................................................................................103 
17.
Administrative, Ethical, and Regulatory Considerations ..............................................103 


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
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Pa ge 9 of 1 4 0  
C o nfi de nti al  
1 7. 1  
Pr ot oc ol A me n d me nts ............................................................................................. 1 0 3  
1 7. 2  
I n d e pe n de nt Et hics C o m mittee/I nstit uti o nal Re vie w B oar d ................................... 1 0 3 
1 7. 3  
I nf or me d C o nse nt F or m .......................................................................................... 1 0 4 
1 7. 4  
P u blicati o ns ............................................................................................................. 1 0 5  
1 7. 5  
Cli nical St u d y Re gistrati o n  ...................................................................................... 1 0 5 
1 7. 6  
Pa y me nt t o S u bjects ................................................................................................ 1 0 5  
1 7. 7  
I n v esti gat or Res p o nsi bilities ................................................................................... 1 0 5 
1 8.
Refere nces  .......................................................................................................................... 1 0 7 
1 9.
A p pe n dices  ......................................................................................................................... 1 1 0 
1 9. 1  
A p pe n di x 1: D ys p ha gia S y m pt o m Q uesti o n naire 
( Pa per a n d El ectr o nic Versi o ns) .............................................................................. 1 1 1 
1 9. 2  
A p pe n di x 2: S oli d F o o d Q uesti o n ( Pa per V ersi o n) ................................................. 1 1 6  
1 9. 3  
A p pe n di x 3: 
 
1 9. 4  
A p pe n di x 4: 
 
1 9. 5  
A p pe n di x 5: E G/ E o D P R O Q uesti o n naire ( Pa per Versi o n) .................................... 1 1 9  
1 9. 6  
A p pe n di x 6:
 ( Pa per V ersi o n) ...................... 1 2 2 
1 9. 7  
A p pe n di x 7: Baseli ne Di et Assess me nt ................................................................... 1 2 8  
1 9. 8  
A p pe n di x 8: C o m m o n Ter mi n ol o g y Criteria f or A d verse E v e nts ( Versi o n 5. 0) .... 1 2 9  
1 9. 9  
A p pe n di x 9: E G D Hist ol o g y ................................................................................... 1 3 0  
1 9. 1 0  A p pe n di x 1 0: Sa m ps o n’s Criteria of A na p h yl a xis .................................................. 1 3 2  
1 9. 1 1  A p pe n di x 1 1: Baseli ne D S Q a n d Bi wee kl y Mea n D S Q Calc ulati o n ...................... 1 3 3  
1 9. 1 2  A p pe n di x 1 2: O pe n- L a bel E xte n de d D osi n g Peri o d ( O pti o nal) ............................. 1 3 5  
1 9. 1 2. 1  S u m mar y of t he O pe n- L a bel E xte n de d D osi n g Peri o d ............................. 1 3 5  
1 9. 1 2. 2  O L E O bjecti ve  .......................................................................................... 1 3 6 
1 9. 1 2. 3  O L E Eli gi bilit y Criteria ............................................................................. 1 3 6 
1 9. 1 2. 3. 1  O L E I ncl usi o n Criteria  ............................................................. 1 3 6 
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19.12.3.2 OLE Exclusion Criteria ............................................................136 
19.12.4 OLE Treatment..........................................................................................136 
19.12.5 OLE Procedures and Guidelines ...............................................................137 
List of Tables 
Table 1 
AK002-014 Schedule of Events ................................................................................43 
Table 2 
Adverse Event Severity per CTCAE .........................................................................88 
Table 3 
Adverse Event Relationship to Study Drug ...............................................................88 
Table 4 
Adverse Event Relationship to Study Procedure .......................................................89 
Table 5 
AK002-014 Open-Label Extended Dosing Period Schedule of Events ..................138 


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 1 1  of 1 4 0  
C o nfi de nti al  
List of A b bre vi ati o ns 
A C  
Aller gic c o nj u ncti vitis  
A D A  
A nti -dr u g a nti b o d y  
A D C C  
A nti b o d y -de pe n de nt cell ular c yt ot o xicit y  
A D L  
Acti vities of dail y li vi n g  
A E  
A d verse e ve nts  
A E SI  
A d verse e ve nts of s pecial i nterest  
A L T  
Ala ni ne a mi n otra nsferase  
A N O V A  
A nal ysis of Varia nce  
A N C O V A  
A nal ysis of c o varia nce  
A nti -I L- 5 
A nti -i nterle u ki n- 5 
A S T  
As partate a mi n otra nsferase  
B MI  
B o d y mass i n de x  
C 
Ce nti gra de  
C B C  
C o m plete bl o o d c o u nt  
C F R  
C o de of Fe deral Re g ulati o n  
CI  
C o nfi de nce i nter val(s)  
c m 
Ce nti meter  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
C U  
C hr o nic Urticaria  
D S Q  
D ys p ha gia S y m pt o m Q uesti o n naire  
E C  
E osi n o p hilic c olitis  
E C G  
Electr ocar di o gra m  
e C R F  
Electr o nic Case Re p ort F or m  
E D C  
Electr o nic Data Ca pt ure (s yste m)  
E G  
E osi n o p hilic gastritis  
E G D  
Es o p ha g o -gastr o -d u o de n osc o p y  
E G E  
E osi n o p hilic gastr oe nteritis  
E GI D  
E osi n o p hilic gastr oi ntesti nal dis or ders  
E LI S A  
E nz y me -li n ke d i m m u n os or be nt assa y 
E o E  
E osi n o p hilic es o p ha gitis  
E o D  
E osi n o p hilic d u o de nitis  
 
 
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EREFS 
Eosinophilic Esophagitis Reference Score for Endoscopic Abnormalities 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
hCG 
human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
hpf 
High power field 
ICE 
Intercurrent event(s)  
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
iDMC 
Independent Data Monitoring Committee 
IgE 
Immunoglobulin E 
IgG1 
Immunoglobulin G1 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IRR 
Infusion-Related Reaction 
ISM 
Indolent systemic mastocytosis 
IRT 
Interactive Response Technology 
ITIM 
Immunoreceptor Tyrosine-based inhibitory motif 
IV 
Intravenous 
JAK 
Janus kinase (inhibitors) 
kg 
Kilogram 
L 
Liter 
LSM 
Least squares means 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
MI 
Multiple imputation  
MITT 
Modified Intent-to-Treat (population) 
mM 
Millimolar 
mL 
Milliliter 


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Pa ge 1 3  of 1 4 0  
C o nfi de nti al  
M M R M  
Mi xe d effects 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  
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 O A E L  
N o -o bser ve d -a d verse -effect-le vel 
O & P  
O va a n d parasite (test)  
O L E  
O pe n -La bel E xte n de d D osi n g ( peri o d)  
P D  
P har mac o d y na mics  
P E  
P h ysical e xa mi nati o n  
PI D  
Patie nt i de ntificati o n n u m ber  
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  
P R O  
Patie nt re p orte d o utc o me  
R E M L  
Restricte d ma xi m u m li keli h o o d  
S A E  
Seri o us a d verse e ve nt 
S A P  
Statistical A nal ysis Pla n  
S D  
Sta n dar d de viati o n  
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   
T E A E SI  
Treat me nt -e mer ge nt a d verse e ve nt  of s pecial 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  
µ L  
Micr oliter  
U L N  
U p per li mit of n or mal  
W H O D D  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
w/ v  
Wei g ht/ v ol u me  
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1.
Protocol Synopsis
Study Title 
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of AK002 in Adult and Adolescent 
Subjects with Active Eosinophilic Esophagitis  
Sponsor 
Allakos Inc., 975 Island Drive, Suite 201, Redwood City, CA 94065 USA 
Number of Sites 
Approximately up to 90 clinical centers globally 
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 circulation. In the tissue, AK002 
induces direct apoptosis of eosinophils and inhibition of mast cells. 
Clinical Background AK002, administered as a monthly intravenous infusion, has previously been 
tested in healthy volunteers and in subjects with indolent systemic mastocytosis 
(ISM), chronic urticaria, 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 subjects with ISM, chronic 
urticaria, severe AC, EG and/or EoD. In these studies, AK002 pharmaco-
dynamic (PD) activity was observed for prolonged periods of time, and the 
AK002 pharmacokinetic (PK) parameters demonstrated a half-life amenable to 
administration every 4 weeks.  
To date, over 200 healthy volunteers and subjects with ISM, chronic urticaria, 
severe AC, mast cell gastritis, and EG and/or EoD 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 
reactions (IRR). Most IRR were mild to moderate; 2 IRR were classified as 
serious but resolved within 24 hours. Transient lymphopenia (a transient 
decrease in lymphocyte count) 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 and is 
consistent with the mechanism of action of AK002. 
In the randomized, double-blind, placebo-controlled, Phase 2 study of AK002 
in 65 subjects with EG and/or EoD, subjects 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.  


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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 and duodenum at the 
high dose and low dose, respectively, versus a 10% increase for subjects 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, 49% in the low dose group versus 24% reduction 
in the placebo group (p=0.0012 and p=0.015, respectively). Improvement in 
symptoms was observed within 24 hours of the first dose of study drug. In 
addition, 70% of high dose treated subjects and 68% of low dose treated 
subjects were treatment responders (defined as >30% improvement in TSS 
and >75% reduction from baseline in tissue eosinophils) versus 5% for 
placebo-treated subjects (p<0.0001).  
Approximately 40% of subjects had concomitant eosinophilic esophagitis 
(EoE). In those subjects, a mean reduction of 95% of eosinophils/high powered 
field (hpf) was observed in the esophageal biopsies of AK002-treated subjects 
versus no change for placebo-treated subjects. Also, 13 of 14 (93%) subjects 
with EoE on AK002 were histologic responders (defined by ≤6 eosinophils/hpf) 
versus 1 of 11 (9%) subjects with EoE on placebo. Dysphagia improved by 
53% in AK002-treated subjects versus 17% in placebo-treated subjects.  
AK002 was well tolerated with IRR being the only adverse event (AE) that 
occurred more frequently in AK002-treated subjects than placebo-treated 
subjects.  
More than 90% of subjects in the Phase 2 study elected to continue into a 
long-term continuation 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 in a 
substantial subset of subjects. No IRR were reported on the first or second 
infusions of AK002 when using this premedication regimen in the extension 
study (AK002-003X). 
Target Disease 
Background and 
Rationale  
Eosinophilic esophagitis represents the most common type of eosinophilic 
gastrointestinal disorders (EGID) and is characterized by chronic inflammation 
due to patchy or diffuse infiltration of eosinophils into layers of the esophagus 
(Collins, 2018; Dellon, 2018). Diagnosis is made based on clinical presentation 
combined with increased tissue eosinophils in biopsy specimens from the 
esophagus, without any other cause for the eosinophilia. Clinical manifestations 
of the disease include dysphagia, food impaction, refractory reflux, abdominal 
discomfort, nausea, and vomiting/regurgitation (Straumann, 2018). The 
symptoms are believed to be due to the release of inflammatory mediators from 
activated eosinophils, and possibly mast cells, resulting in inflammatory 
changes, including strictures (Abonia, 2010; Furuta, 2014). Active EoE has 
been defined by the presence of intramucosal eosinophilia with a peak count of 
≥15 eosinophils/hpf (Dellon, 2018).  


Protocol AK002-014 
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Target Disease 
Background and 
Rationale cont. 
Chronic inflammation and progressive fibrosis in EoE lead to narrow caliber 
esophagus and formation of strictures. At the time of diagnosis, up to 67% of 
adults and 16% of children already have fibrostenotic disease (Warners, 2018). 
The pathogenesis of EoE is immune-mediated, triggered in response to food or 
environmental antigens. The initial Th2 inflammatory response with the release 
of various cytokines including IL-4, IL-5, IL-13, and Eotaxin-3 leads to 
trafficking of eosinophils to the esophageal mucosa, which is normally devoid 
of any eosinophils (Collins, 2018). The inflammatory infiltrate in EoE is most 
notable for the presence of eosinophils and mast cells, which appear to be the 
primary drivers of tissue damage and eventual development of fibrosis 
(Abonia, 2010; Collins, 2018).  
EoE is currently estimated to affect 4 out of every 10,000 persons in the United 
States (Dellon, 2014; Jensen, 2016). The incidence and prevalence of EoE is 
rapidly increasing, though whether this represents a true increase in incidence 
or is due to increased awareness and recent consensus on guidelines for 
diagnosis is unknown (Syed, 2012). Patients may also have concomitant atopic 
diseases like food allergy, asthma, and atopic dermatitis, which further impact 
patients’ quality of life and contribute to health care costs. Also, 8% to 10% of 
patients with EoE may develop other eosinophilic gastrointestinal diseases like 
EG and/or EoD (Jensen, 2016).  
There are no FDA-approved treatments for EoE. Current therapies and disease 
management include dietary elimination, proton pump inhibitors (PPI), and 
topical or systemic steroids. Partial benefit has been observed with dietary 
elimination and PPI, but 40% to 50% of patients are refractory to these 
measures (Arias, 2014; Dellon, 2018; Dellon, Speck, 2014; Katz, 2013; 
Molina-Infante, 2016). In addition, responders to dietary elimination have 
demonstrated poor long-term adherence (Lucendo, 2013; Philpott, 2016; 
Reed, 2017). Corticosteroids, topical or systemic, have been shown to provide 
symptom relief but are not appropriate for long-term treatment due to numerous 
side effects and associated risks. Both topical (swallowed) and systemic 
corticosteroids have been shown to cause infection, adrenal insufficiency, 
bone demineralization, diminished growth, and cataracts (Furuta, 2015; 
Konikoff, 2006). Occasionally, in treatment-refractory cases, 
immunomodulatory biologics are attempted, but the role of biologics in 
treatment algorithms remains to be defined (Assa’ad, 2011; Clayton, 2014; 
Hirano, 2019; Hirano, 2017; Markowitz, 2018; Rothenberg, 2014; 
Spergel, 2012; Straumann, 2010). Given the chronic and progressive nature of 
the disease and lack of approved therapies, better treatment options are clearly 
needed to manage EoE. 
AK002 was tested in a randomized, double-blind, placebo-controlled, Phase 2 
study in 65 subjects with EG and/or EoD. Subjects were randomized 1:1:1  


Protocol AK002-014 
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Target Disease 
Background and 
Rationale cont. 
to 1 of 3 dose groups: placebo, low dose regimen (4 monthly doses of AK002 
at 0.3, 1, 1, and 1 mg/kg), or high dose regimen (4 monthly doses of AK002 at 
0.3, 1, 3, and 3 mg/kg). All primary and secondary endpoints were met. 
There was a 97% and 92% mean reduction in eosinophils in the stomach and 
duodenum for the high dose group and low dose group, respectively, versus a 
10% increase for placebo (p<0.0001). The reduction of eosinophils was 
associated with a statistically significant reduction in TSS8 of 58% in the high 
dose group, 49% in the low dose group, versus 24% reduction in the placebo 
group (p=0.0012).  
Approximately 40% of subjects with EG and/or EoD in the Phase 2 study had 
concomitant EoE. Of these subjects with concomitant EoE, those treated with 
AK002 had a 95% mean reduction in eosinophil count in esophageal biopsies 
versus no change in subjects treated with placebo. The reduction of eosinophils 
was associated with a 53% reduction in dysphagia on AK002 versus 17% on 
placebo. In addition, 13 of the 14 EoE subjects receiving AK002 were 
KLVWRORJLFDOUHVSRQGHUVGHILQHGDVHRVLQRSKLOVKSIDW:HHN 
By markedly reducing the number of blood and tissue eosinophils and 
inhibiting the activation of mast cells, AK002 may be useful in the treatment of 
patients with EoE. This Phase 2/3 study will evaluate the safety, tolerability, 
and clinical benefit of repeat doses of AK002 in adult and adolescent subjects 
with symptomatic EoE. Assessment of clinical benefit will include 
symptomatic, endoscopic, and histological improvement in disease. 
Rationale for Dose 
Selection 
Based on experience with AK002 in healthy volunteers and in subjects with 
ISM, chronic urticaria, severe AC, and EG and/or EoD, the proposed AK002 
dose regimen of 6 total doses is 1 mg/kg for the first infusion, followed by 
either 1 mg/kg or 3 mg/kg administered every 4 weeks for 5 subsequent 
infusions. Subjects who complete randomized, double-blind, placebo-controlled 
treatment (all 6 doses of placebo or AK002) may have the option to receive 
6 doses of open-label AK002 through participation in the Open-Label Extended 
Dosing (OLE) Period of the study.  
CCI


Protocol AK002-014 
Amendment 6 
Date: 2FW 2021 
Allakos Inc. 
Page 18 of 140 
Confidential 
Rationale for Dose 
Selection cont. 
Twelve to 24 hours prior to the first dose of study drug, subjects will self-
administer oral prednisone premedication (40 mg if body weight is <40 kg, 
60 PJLIERG\ZHLJKWLVNJDQGNJRUPJLIERG\ZHLJKWLV
 kg). 
The proposed dose regimen in this EoE study is 6 doses of AK002 or placebo: 
1 mg/kg for the first infusion, followed by either 1 mg/kg or 3 mg/kg 
administered every 4 weeks for 5 subsequent infusions (with the option to 
receive 6 additional infusions of open-label AK002 through the OLE period). 
Number of Subjects 
Approximately 300 subjects with symptomatic EoE will be randomized 1:1:1 to 
receive 1 of 3 dose regimens in a double-blind fashion:  
x
6 doses of placebo.
x
Low dose regimen: 1 mg/kg AK002 administered every 4 weeks for
6 doses.
x
High dose regimen: 1 mg/kg AK002 for the first dose followed by 3 mg/kg
AK002 administered every 4 weeks for 5 subsequent doses.
The power calculations for the number of subjects is described in Section 15.2, 
Sample Size. 
Subjects who successfully complete the randomized, double-blind, placebo-
controlled treatment and the Day 169 visit may have the option to receive 
6 doses of open-label AK002 through participation in the OLE period of the 
study. 
CCI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 19 of 140 
Confidential 
Study Design 
This is a Phase 2/3, multicenter, randomized, double-blind, placebo-controlled 
study to evaluate the safety, tolerability, and clinical benefit of AK002 in adult 
and adolescent subjects with active and biopsy-proven EoE. Subjects enrolled 
in the study will receive 6 infusions of placebo or AK002 administered every 
4 weeks and will be followed for 8 weeks after the last dose.  
Subjects who successfully complete the randomized, double-blind, placebo-
controlled treatment period of the study including the Day 169 visit may have 
the option to receive 6 doses of open-label AK002 through participation in the 
OLE period of the study.  
Subjects will be consented and then screened for 14 to 60 days (or a maximum 
of 35 days after the Screening EGD, whichever is shorter). During the 
screening period, a baseline, stable regimen of PPI and/or dietary intake will be 
established, if needed, and baseline disease activity data will be collected. 
Swallowed topical and systemic corticosteroids will not be allowed. Subjects 
who meet eligibility criteria can be enrolled into the study. Subjects who do not 
meet all eligibility criteria at screening, or who qualify at screening but are not 
enrolled, may be assigned a new patient identification number and rescreened 
once. Subjects rescreened within 30 days of signing initial consent will not 
need to reconsent if there were no changes to the ICF. 
Prior to the first dose of study drug, subjects will be premedicated with oral 
prednisone (40 mg if body weight is <40 kg, 60 mg if body weight is ≥40 kg 
and <60 kg, or 80 mg if body weight is ≥60 kg). Subjects will self-administer 
oral prednisone 12–24 hours prior to the start of the first infusion only. 
Eligible subjects will receive the first dose of placebo or AK002 (1 mg/kg) on 
Day 1 and will remain confined to the clinic for at least 1 hour of observation 
(or greater, as per Investigator’s discretion) following the end of the infusion. 
If the study drug is well tolerated (no stopping rules being met), subjects will 
continue to receive doses of placebo, 1 mg/kg AK002, or 3 mg/kg AK002 on 
Days 29, 57, 85, 113, and 141 for a total of 6 doses. Subjects will remain at the 
site for at least 1 hour of observation (or longer, as per the Investigator’s 
discretion) after each dose. In the event of an IRR, the subject may require 
prolonged observation (>1 hour or until the symptoms resolve), as per the 
Investigator’s discretion. Subjects will also be instructed to immediately 
contact the study doctor if any reactions occur after discharge. 
During the treatment period, subjects will return to the site for study visits as 
described in the Schedule of Events (Table 1). After completion of the Day 169 
visit, the Investigator will evaluate whether the subject is eligible for the OLE 
period. 


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
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Confidential 
Study Design cont. 
Only subjects who successfully complete the double-blind treatment period of 
the study including the Day 169 visit will have the option to receive 6 doses of 
open-label AK002 through participation in the OLE period, provided all 
eligibility criteria for the OLE period are satisfied.  
Subjects who are not eligible for (or who choose not to participate in) the OLE 
period will be followed for approximately 8 weeks after the last dose per the 
Schedule of Events (Table 1), including the Day 169 visit (4 weeks after the 
last dose) and the Day 197 visit (8 weeks after the last dose). 
Eligible subjects who choose to participate in the OLE period will begin 
following the OLE Schedule of Events (Table 5) and will receive the first dose 
of open-label AK002 approximately 1 week following Day 169. 
If absolute lymphocyte and/or eosinophil counts have not recovered (to normal 
range or baseline levels) by the Day 197 visit (or the Day 372 visit for subjects 
participating in the OLE period), extended follow-up visits are required 
approximately every 4 weeks to monitor blood counts until they recover. 
The study design is summarized as follows: 
•
A 14 to 60-day screening period (or a maximum of 35 days after the
Screening EGD, whichever is shorter) with evaluations for eligibility,
including baseline disease activity (by daily Patient Reported Outcome
[PRO] questionnaire) and Esophago-Gastro-Duodenoscopy (EGD) with
biopsy.
•
Prior to the first dose of study drug, subjects will be premedicated with
oral prednisone (40 mg if body weight is <40 kg, 60 mg if body weight is
≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg). Subjects will self-
administer prednisone 12–24 hours prior to the first infusion only.
•
Eligible subjects will receive 6 doses of AK002 (or placebo) by IV infusion
on Days 1, 29 (±3), 57 (±3), 85 (±3), 113 (±3), and 141 (±3).
•
A repeat EGD with biopsy will be performed on Day 169 (±3) or
approximately 4 weeks after last dose if subject is terminated early.
•
After completion of the Day 169 visit, the Investigator will evaluate
whether the subject is eligible for OLE.
•
Subjects who are eligible and choose to participate in the OLE period will
begin following the OLE Schedule of Events (Table 5) on Day 176 (±3).
The OLE period will include 6 doses of open-label AK002 administered on
Days 176 (±3), 204 (±3), 232 (±3), 260 (±3), 288 (±3), and 316 (±3) and
post-treatment follow-up visits on Day 344 (±7) and Day 372 (±7).


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 21 of 140 
Confidential 
Study Design cont. 
•
Subjects who are not eligible for (or who choose not to participate in) the
OLE period will be followed for approximately 8 weeks after the last dose
per the Schedule of Events (Table 1), including the Day 169 visit (4 weeks
after the last dose) and the Day 197 visit (8 weeks after the last dose).
•
If absolute lymphocyte and/or eosinophil counts have not recovered by
Day 197 (or Day 372 for subjects in the OLE period), subjects will return
approximately every 28 days for extended follow-up until counts recover.
•
Total study duration is approximately 33–36 weeks (or 58–61 weeks for
subjects participating in the OLE period), though the study duration could
be extended for monitoring absolute lymphocyte and/or eosinophil counts
(as described above).
Primary Efficacy 
Objective 
To evaluate the efficacy of AK002 in adult and adolescent subjects with active 
EoE when compared to placebo, efficacy endpoints will be co-primary: 
1)
The proportion of subjects who achieve a peak esophageal intraepithelial
count of ≤6 eosinophils/hpf at Week24.
2)
Mean change in Dysphagia Symptom Questionnaire (DSQ) score from
Baseline to Weeks 23–24.
Secondary 
Objectives 
To further evaluate the efficacy of AK002 in adult and adolescent subjects with 
active EoE when compared to placebo as measured by: 
1)
Percent change in peak esophageal intraepithelial eosinophil count at
Week 24.
2)
Proportion of subjects achieving peak esophageal intraepithelial eosinophil
count of ≤1 eosinophil/hpf at Week 24.
3)
Proportion of subjects achieving peak esophageal intraepithelial eosinophil
count of <15 eosinophils/hpf at Week 24.
4)
Proportion of treatment responders when a responder is a subject
achieving >30% reduction in symptoms (DSQ) at Weeks 23–24 and
achieving a peak intraepithelial eosinophil count of ≤6 eosinophils/hpf at
Week 24.
5)
Proportion of subjects with >50% reduction in DSQ score from Baseline
to Weeks 23–24.
6)
Percent change in DSQ score from Baseline to Weeks 23–24.
7)
Change in biweekly mean DSQ over time.
8)
Change in EoE Reference Score for Endoscopic Abnormalities from
Baseline to Week 24.


Protocol AK002-014 
Amendment 6 
Date: 2FW 2021 
Allakos Inc. 
Page 22 of 140 
Confidential 
Exploratory 
Objectives 
To further evaluate the pharmacodynamic effect of AK002 in subjects with 
active EoE when compared to placebo as measured by: 
1)
Change in 
 score from Baseline to
Week 24.
2)
Change in
 from Baseline to Week 24.
3)
Change in 
 from Baseline to Week 24.
Safety Objectives 
To evaluate the safety and tolerability of AK002 in adult and adolescent 
subjects with active EoE by determining AE incidence and severity, study 
withdrawals due to AE, changes in vital signs and laboratory tests including 
immunogenicity, changes in concomitant medication beginning on or after the 
first infusion of study drug, and other safety parameters. 
Subject Selection 
Criteria 
Inclusion Criteria 
Subjects with active EoE are eligible to enroll in the study if all of the 
following criteria are met: 
1)
0DOHRUIHPDOHDJHGDQG\HDUVDWWKHWLPHRIVLJQLQJ,&)
2)
Confirmed diagnosis of EoE and intraepithelial eosinophilic infiltration of
HRVLQRSKLOVKSILQKSIIURPDELRSV\FROOHFWHGGXULQJWKH6FUHHQLQJ
EGD without any other cause for the esophageal eosinophilia.
3)
Baseline DSQ (biweekly mean DSQ) VFRUHRIIURPWKHODVWZHHNVRI
screening (the 14 days prior to the first dose) per the validated algorithm in
Appendix 11.
4)
History (by subject UHSRUWRIDQDYHUDJHRIHSLVRGHVRIG\VSKDJLDZLWK
intake of solid foods per week during the 4 weeks prior to screening.
5)
Subjects must have failed or not be adequately controlled on standard of
care treatments for EoE symptoms, which could include PPI, systemic or
topical corticosteroids, and/or diet, among others.
6)
If on an allowed treatment for EoE (per Section 8.2), stable dose for at
least 4 weeks prior to screening and willingness to continue that dose for
the study duration.
7)
If subject is on preexisting dietary restrictions, willingness to maintain
dietary restrictions throughout the study, as much as possible.
8)
Able and willing to comply with all study procedures.
CCI
CCI
CCI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 23 of 140 
Confidential 
Subject Selection 
Criteria cont. 
Inclusion Criteria cont. 
9)
Female subjects 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 either agree to
use dual methods of contraception, have a partner who had a vasectomy,
or agree to abstain from sexual activity from screening until the end of the
study, or for 120 days following the last dose of study drug, whichever is
longer.
Non-vasectomized male subjects with female partners of childbearing
potential must agree to either abstain from sexual activity or agree to use a
highly effective method of contraception from screening until the end of
the study or for 120 days following 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 at any time during study participation.
Exclusion Criteria 
Subjects will be excluded if they meet any of the following criteria: 
1)
Concomitant moderately or severely symptomatic EG and/or EoD*,
defined as:
–
≥30 eosinophils/hpf in 5 hpf in the stomach (EG) and/or
≥30 eosinophils/hpf in 3 hpf in the duodenum (EoD) without any other
cause for eosinophilia as determined by central histology assessment
of biopsies collected during the Screening EGD
and 
–
EG/EoD PRO Questionnaire weekly average single symptom score of
≥3 during the last 2 weeks of screening for 1 of the following
symptoms: abdominal pain, nausea, and/or diarrhea.
*
This exclusion criterion is only applicable to sites actively enrolling
subjects in the AK002-016 study. If a site is not actively screening and
enrolling subjects in the AK002-016 study, then this exclusion
criterion is not applicable.
2)
Causes of esophageal eosinophilia other than EoE or one the following:
hypereosinophilic syndrome, eosinophilic granulomatosis with
polyangiitis, or peripheral blood absolute eosinophil count of
>1500 eosinophils/µL.
3)
History of inflammatory bowel disease, celiac disease, achalasia, and/or
esophageal surgery.


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 24 of 140 
Confidential 
Subject Selection 
Criteria cont. 
Exclusion Criteria cont. 
4)
Any esophageal stricture unable to be passed with a standard diagnostic
9 mm to 10 mm upper endoscope or any critical esophageal stricture that
requires dilation during screening.
5)
History of bleeding disorders or esophageal varices.
6)
History of malignancy; except carcinoma in situ, early stage prostate
cancer, or non-melanoma skin cancers. However, cancers that have been in
remission for more than 5 years and are considered cured, can be enrolled
(with the exception of breast cancer). All history of malignancy (including
diagnosis, dates, and compliance with cancer screening recommendations)
must be documented and certified by the Investigator, along with the
statement that in their clinical judgment the tissue eosinophilia is
attributable to EGID, rather than recurrence of malignancy.
7)
Active Helicobacter pylori infection (as determined by central histology
staining of the biopsy collected during the Screening EGD), unless treated
and confirmed to be negative prior to randomization and symptoms remain
consistent.
8)
Positive Ova and Parasite test at screening, seropositive for Strongyloides
stercoralis at screening, and/or treatment for a clinically significant
helminthic parasitic infection within 6 months of screening.
9)
Seropositive for HIV or hepatitis at screening, except for vaccinated
subjects or subjects with a history of hepatitis that has since resolved.
10) Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
11) Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI,
and/or diet therapy within 4 weeks prior to screening.
12) Use of oral corticosteroids (swallowed topical or systemic corticosteroids)
within 8 weeks prior to screening.
13) Use of any biologics or medications that may interfere with the study, such
as immunosuppressive or immunomodulatory drugs including
azathioprine, JAK inhibitors, 6-mercaptopurine, methotrexate,
cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor, e.g., dupilumab),
anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g., benralizumab),
anti-IL-13 (e.g., lebrikizumab), anti-IgE (e.g., omalizumab), within
12 weeks prior to screening.
14) Participation in a concurrent interventional study with the last intervention
occurring within 30 days prior to administration of study drug or 90 days
or 5 half-lives, whichever is longer, for biologic products.


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 2 5  of 1 4 0  
C o nfi de nti al  
S u bject Selecti o n 
Criteri a c o nt.  
E xcl usi o n Criteri a c o nt.  
1 5)
Vacci nati o n wit h li ve atte n uate d vacci nes ≤3 0 da ys pri or t o i nitiati o n of
treat me nt i n t he st u d y, d uri n g t he treat me nt peri o d, or vacci nati o n
e x pecte d ≤5 half -li ves ( ≤4 m o nt hs) f oll o wi n g st u d y dr u g a d mi nistrati o n
( wit h t he e xce pti o n of a C O VI D- 1 9 vacci ne a ut h orize d b y t he F D A or
ot her a p plica ble re g ulat or y a ge nc y).
1 6)
Treat me nt wit h c he m ot hera p y or ra di ot hera p y i n t he prece di n g 6 m o nt hs.
1 7) Prese nce of a b n or mal la b orat or y val ues c o nsi dere d b y t he I n vesti gat or t o
be cli nicall y si g nifica nt.
1 8)  A n y disease, c o n diti o n ( me dical or s ur gical), or car diac a b n or malit y,
w hic h i n t he o pi ni o n of t he I n vesti gat or, w o ul d place t he s u bject at
i ncrease d ris k.
1 9)  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.
2 0)  W o me n w h o are pre g na nt, breastfee di n g, or pla n ni n g t o bec o me pre g na nt
w hile partici pati n g i n t he st u d y.
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 Me dical
M o nit or ma kes t he s u bject u ns uita ble f or e nr oll me nt.
Test Pr 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 V i njecti o n. T he i njecti o n will be a d mi nistere d 
t hr o u g h a n i nf usi o n p u m p. A K 0 0 2 a n d place b o are f or m ulate d i n 
 
p H 6. 0, i n Water f or I njecti o n. 
Pri or t o t he first d ose of st u d y d r u g, s u bjects will be pre me dicate d wit h oral 
pre d nis o ne ( 4 0 m g if b o d y wei g ht is < 4 0 k g, 6 0 m g if b o d y wei g ht is ≥4 0 k g 
a n d < 6 0 k g, or 8 0 m g if b o d y wei g ht is ≥6 0 k g). S u bjects will self -a d mi nister 
oral pre d nis o ne 1 2 – 2 4 h o urs pri or t o t he start of t he firs t i nf usi o n o nl y.  
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 
s u bject’s b o d y wei g ht a n d a d mi nistere d o ver ≥4 h o urs o n Da y 1.  
S u bse q ue nt i nf usi o ns of place b o or A K 0 0 2 at a d ose of 1 m g/ k g or 3 m g/ k g 
will be pre pare d o n Da y  2 9 ( ± 3), Da y 5 7 ( ± 3), Da y 8 5 ( ± 3), Da y 1 1 3 ( ± 3), a n d 
Da y  1 4 1 ( ± 3). De pe n di n g o n t he s u bject’s t olera nce of t he first a n d s u bse q ue nt 
i nf usi o ns (a n d at t he I n vesti gat or’s discreti o n), t he sec o n d i nf usi o n ca n be gi ve n 
o ver ≥3 h o urs, a n d t he s u bse q ue nt 4 i nf usi o ns ca n be gi ve n o ver ≥2 h o urs.  
D ur ati o n of S u bject 
P artici p ati o n  
T he t otal st u d y d urati o n f or eac h s u bject will be eit her 3 3 – 3 6 wee ks or 
5 8- 6 1 wee ks, i ncl u di n g a n d de pe n di n g o n:
•
Scree ni n g peri o d of 1 4 – 6 0 da ys ( or a ma xi m u m of 3 5 da ys after t he
Scree ni n g E G D, w hic he ver is s h orter) pri or t o st u d y dr u g a d mi nistrati o n.
C CI
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 2 6  of 1 4 0  
C o nfi de nti al  
D ur ati o n of S u bject 
P artici p ati o n c o nt.  
•
Treat me nt peri o d of 2 4 wee ks ( ± 3 da ys) be gi n ni n g t he da y of t he first d ose
a n d e n di n g 4 wee ks after t he last d ose.
•
O pti o nal O pe n - La bel E xte n de d D osi n g Peri o d of 2 8 wee ks ( ± 3 da ys), or
F oll o w- u p peri o d of 4 wee ks ( ± 3 da ys).
Re gar dless of w het her a s u bject partici pates i n t he O L E peri o d or n ot, all 
s u bjects will be f oll o we d f or 8 wee ks after t he last d ose of st u d y dr u g. If 
l y m p h oc yte or e osi n o p hil c o u nts ha ve n ot rec o vere d b y Da y 1 9 7 or Da y 3 7 2 f or 
s u bjects partici pati n g i n t he O L E peri o d, s u bjects will ret ur n e ver y 2 8 da ys f or 
e xte n de d f oll o w- u p u ntil c o u nts ha ve rec o vere d. 
S afet y E v al u ati o ns 
Safet y a n d t olera bilit y will be asse sse d t hr o u g h o ut t he st u d y b y m o nit ori n g a n d 
e val uati n g A E, i ncl u di n g a n y c o m plicati o ns res ulti n g fr o m t he i ntra ve n o us 
i nf usi o n. All T E A E will be c ollecte d fr o m t he start of st u d y dr u g a d mi nistrati o n 
t hr o u g h Da y 1 9 7 ( ± 3 da ys) or Da y 3 7 2 (f or s u bjects partici pati n g i n t he O L E 
peri o d) or Earl y Ter mi nati o n.  
Se verit y of A E will be assesse d usi n g t he Nati o nal Ca ncer I nstit ute C o m m o n 
Ter mi n ol o g y Criteria f or A d verse E ve nts ( 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, i ncl u di n g a nti-
dr u g a nti b o d y t o A K 0 0 2, c o m plete bl o o d c o u nts, c he mistries, a n d uri nal yses as 
well as p h ysical e xa ms a n d vit al 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. T he 
safet y m o nit or will re vie w bli n de d safet y data a n d escalate t o t he Me dical 
M o nit or as a p pr o priate.  
A n i n de pe n de nt Data M o nit ori n g C o m mittee (i D M C) has bee n c o n ve ne d a n d 
will meet at re g ularl y sc he d ule d i nter vals i n acc or da nce wit h t he i D M C c harter.  
D uri n g t he peri o d of e xte n de d f oll o w -u p, data c ollecti o n will be li mite d t o 
he mat ol o g y, seri o us a d verse e ve nts, a n d a d verse e ve nts of s pecial i nterest.  
Effic ac y a n d 
P h ar m ac o d y n a mic 
E v al u ati o ns 
Bi o psies of es o p ha geal 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 a n d per t he 
. A d diti o nall y, t he se verit y of e n d osc o pic 
fi n di n gs will be e val uate d per t he E osi n o p hilic Es o p ha gitis Refere nce Sc ore f or 
E n d osc o pic A b n or malities ( E R E F S) d uri n g t he E G D. T he e osi n o p hil c o u nts i n 
peri p heral bl o o d will be c ollecte d. 
Dail y self -a d mi nistrati o n of a disease -s pecific patie nt q uesti o n naire, t he D S Q, 
will be use d t o e val uate si g ns a n d s y m pt o ms ass ociate d wit h E o E. If Q uesti o n  1 
of t he D S Q is a ns were d “ N o,” t he s u bject will recei ve t he S oli d F o o d Q uesti o n 
(A p pe n di x 2 ) after t he y c o m plete a n d s u b mit t he D S Q. S u bjects will rate  
 
  
 
C CI
C CI
C CI


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Pharmacokinetic 
Evaluations 
Blood (serum) will be collected for assessment of AK002 concentrations using 
a validated enzyme-linked immunosorbent assay method. Pharmacokinetic 
blood samples will be obtained on Days 1, 8, 15, 29, 57, 85, 113, 141, 169, and 
197 (or ET). On dosing days (Days 1, 29, 57, 85, 113, and 141), blood for PK 
will be collected predose. 
Blood (serum) will be collected for assessment of AK002 anti-drug antibodies 
(ADA) using a validated assay method. ADA blood samples will be obtained 
predose on Days 1, 29, 57, 85, 113, 141, and 197 (or ET), and in the event of a 
suspected immunogenicity-related AE. 
Sample Size 
Calculation 
First Co-Primary Endpoint: A sample size of 8 subjects/treatment group will 
provide 90% power to demonstrate a statistically significant difference between 
any AK002 dose group and placebo in achieving histologic response (defined 
as the peak esophageal intraepithelial eosinophil count ≤6 cells/hpf) at 
Week 24. This calculation is based on the AK002-003 study in which 90% of 
AK002 subjects and 10% of placebo subjects achieved the histologic response 
at Day 99. The hypothesized treatment effect of 80% yielded a small number of 
subjects per group for the first co-primary endpoint. 
Second Co-Primary Endpoint: A sample size of 86 subjects/treatment group 
will provide 90% power to demonstrate a statistically significant difference 
between any AK002 dose group and placebo treatment group in mean absolute 
change in DSQ score from Baseline to Weeks 23–24. This calculation is based 
on the baseline score of 30 ± 15 (mean ± Standard Deviation [SD]) reported in 
the literature, and an expected mean reduction of 15 in any AK002 dose group 
and 7.5 in the placebo group, and a SD of 15 for the change from baseline 
(Dellon, 2017; Hirano, 2019; Hudgens, 2017).  
Consequently, approximately 100 subjects/treatment group will be included for 
a total of 300 subjects, driven by the second co-primary endpoint and potential 
14% dropout rate. 
Statistical Analysis 
All subjects who received study medication will be included in the Safety 
Population for safety analysis. Subjects who are randomized and have received 
at least 1 dose of study medication will be included in the modified Intent-to-
Treat (mITT) population for efficacy analysis.  
Subjects who meet mITT criteria and do not have significant protocol 
deviations interfering with efficacy assessment will be included in the Per 
Protocol (PP) population.  
The study statistician and study team will review protocol deviations to identify 
subjects to be excluded from the PP analysis population. The mITT population 
will be used for all efficacy analysis, and the PP population will be used for 
supplementary analyses of the primary endpoints and select secondary 
endpoints. 


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Statistical Analysis 
cont. 
All subject data will be listed for the double-blind placebo-controlled portion of 
the study. When appropriate, summary statistics of number of non-missing 
values, mean, median, standard deviation, minimum, and maximum will be 
computed for continuous variables and summary statistics of number and 
proportion will be computed for categorical variables.  
Two-sided 95% confidence intervals (CI) will be provided for the mean and 
proportion. No formal statistical inferences will be made for safety parameters. 
Safety data will be summarized for each treatment group as well as for the 
2 active dose groups combined, unless otherwise specified.  
Baseline for all safety and efficacy endpoints is defined as the last observations 
before administration of the first IV infusion of study drug, unless otherwise 
specified. 
Subjects will be stratified at randomization based on age strata (12–17 and 
≥18 years) and baseline DSQ score (≤30 and >30).  
Statistical analysis will be performed on completion of the double-blind, 
placebo-controlled portion of the study. On completion of the OLE period, 
additional statistical analyses will be performed on data collected in that period 
and for the entirety of the study. 
Efficacy Analysis: To evaluate the clinical benefit of AK002 in adult and 
adolescent subjects with active EoE when compared to placebo, efficacy 
endpoints will be co-primary. 
The first co-primary endpoint is the proportion of subjects who achieve a peak 
esophageal intraepithelial count of ≤6 eosinophils/hpf at Week 24. The 
endpoint will be analyzed using Fisher’s exact test comparing the AK002 group 
and placebo group for the proportion of treatment responders. Subjects who 
experience an intercurrent event (ICE, e.g., exit the study prematurely or 
initiate prohibited medication or therapeutic EGD procedure) prior to the end of 
Week 24 will be treated as non-responders.  
The second co-primary endpoint is the mean absolute change in DSQ score 
from Baseline to Weeks 23–24. The DSQ score will be analyzed using 
ANCOVA with treatment as a factor, and Baseline DSQ and age strata as 
covariates. Baseline DSQ will be calculated using the DSQ scoring algorithm 
for all daily DSQ assessments collected during the 2 weeks prior to the first 
infusion of study drug.  
Data on subjects who experience an ICE (e.g., exit the study prematurely or 
initiate prohibited medications or therapeutic EGD procedure) prior to the end 
of Week 24 will be set to missing. Missing DSQ will be imputed using the 
Markov Chain Monte Carlo (MCMC) method.  


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Statistical Analysis 
cont. 
Two sensitivity analyses will be conducted for the second co-primary endpoint. 
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 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 utilize the tipping point method. In this method, 
the missing biweekly DSQ 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).  
Change in continuous outcomes will be analyzed using a mixed model for 
repeated measures (MMRM) and will include fixed effects for age, baseline 
value, treatment, visit, and the treatment by visit interaction and allow for 
random subject effects. Treatment and visit will each be fitted as categorical 
variables. The model will assume unstructured covariance structure. If the 
model with unstructured covariance does not converge or it is determined to be 
inappropriate as outlined in the Guerin and Stroup study (Guerin, 2000), then 
other covariance structures will be considered to model the within-subject 
errors. The selection of the covariance structure for the final model will be 
handled in a hierarchical fashion, with the order being heterogeneous Toeplitz, 
AR(1), and compound symmetry, respectively. 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. The 
least squares means with 95% CI will be presented for each treatment*week 
cross-classification.  
A hierarchical procedure will be used to control the overall Type-I error rate at 
0.05 for the primary endpoint and the secondary endpoints across the 2 AK002 
dose regimens versus placebo. Each hypothesis will be formally tested only if 
the preceding hypothesis is significant at the 2-sided 0.05 significance level. 
The hierarchical testing order (all comparisons are with placebo) is detailed in 
the Statistical Analysis Plan. 
Percent change in peak esophageal intraepithelial eosinophil count at Week 24 
will be analyzed by ANCOVA with age strata, baseline eosinophil count, and 
baseline DSQ as covariates.  
The proportion of subjects achieving peak esophageal intraepithelial eosinophil 
count of ≤1 eosinophils/hpf and <15 eosinophils/hpf at Week 24 will each be 
analyzed using Fisher’s exact test. 


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Statistical Analysis 
cont. 
The proportion of Treatment Responders, defined by subjects achieving >30% 
reduction in DSQ score (Weeks 23–24) and a peak esophageal intraepithelial 
eosinophil count of ≤6 eosinophils/hpf at Week 24, will be analyzed using 
Fisher’s exact test. 
The proportion of subjects with >50% reduction in DSQ score from Baseline to 
Weeks 23–24 will be analyzed using the Cochran-Mantel-Haenszel test. The 
randomization stratum (age strata and baseline DSQ) will be used as the 
stratification factor for the analysis.  
Change in DSQ scores from Baseline to Weeks 23–24 will be analyzed 
similarly to that for the change in DSQ scores.  
The analysis of change in biweekly mean DSQ over time will employ the 
MMRM model similarly described above.  
Change in EoE Reference Score for Endoscopic abnormalities will employ the 
MMRM model similarly described above 
Safety Analysis: Subject incidence of treatment-emergent adverse events 
(TEAE) will be tabulated by MedDRA system organ class and preferred term 
and by severity and treatment relationship. Serious TEAE and TEAE leading to 
study discontinuation will be listed with pertinent information.  
Change from Baseline in laboratory tests will be summarized with descriptive 
statistics. Shift table will be presented. Vital signs will be summarized 
descriptively over time. Details of the analytical methods will be included in 
the Statistical Analysis Plan. 


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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 eosinophils, mast cells and, at lower levels, on basophils. 
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 Siglec-8-positive target cells in vivo and in vitro. 
2.2 
Overview of Nonclinical Studies 
AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody 
directed against 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. 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 esophagitis (EoE). 
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 
immunoglobulin E (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. 


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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 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 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 a monthly intravenous infusion, has previously been tested in healthy 
volunteers and in subjects with indolent systemic mastocytosis (ISM), chronic urticaria, severe 
allergic conjunctivitis (AC), mast cell gastritis, and eosinophilic gastritis (EG) and/or 
eosinophilic duodenitis (EoD), referred to as eosinophilic gastroenteritis (EGE) in previous 
studies.  
Multiple doses of 3 mg/kg have been given to subjects with ISM, chronic urticaria, severe AC, 
mast cell gastritis, and EG and/or EoD. In these studies, AK002 pharmacodynamic (PD) activity 
was observed for prolonged periods of time and the AK002 pharmacokinetic (PK) parameters 
demonstrated a half-life amenable to administration every 4 weeks.  
To date, 51 healthy volunteers (36 on AK002, 15 on placebo), 25 subjects with ISM, 47 subjects 
with chronic urticaria (including spontaneous and inducible), 30 subjects with severe AC, 
8 subjects with mast cell gastritis, and 65 subjects with EG and/or EoD (43 on AK002 and 22 on 
placebo) have been enrolled in clinical studies. 


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In general, AK002 was well tolerated. The most common treatment-emergent adverse event 
(TEAE) observed was infusion-related reactions (IRR). Most IRR were mild to moderate and 
2 IRR (1 in the healthy volunteer study and 1 in the AK002-003 study) were serious but resolved 
within 24 hours. Common symptoms of IRR were headache, nausea, sweating, flushing, and 
redness. Most IRR occurring 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, chronic urticaria, severe AC, and EG and/or EoD; 
fewer adverse events (AE) were reported during the second and subsequent infusions when 
compared to the first infusion. 
In all studies, a transient decrease in lymphocyte counts was observed after the AK002 infusion 
(usually resolving within 1 day) that was not associated with any clinical consequence, and a 
sustained depletion of eosinophils was observed that is 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 subjects with 
EG and/or EoD, subjects 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 mean reduction of 97% and 
92% in eosinophils in the stomach and duodenum at the high dose and low dose AK002-treated 
subjects, respectively, versus a 10% increase for placebo-treated subjects (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, 49% in the low dose group versus 24% 
in the placebo group (p=0.0012 and p=0.015, respectively). Improvement in symptoms was 
observed within 24 hours of the first dose of study drug. In addition, 70% of high dose 
AK002-treated subjects and 68% of low dose AK002-treated subjects were treatment responders 
(defined as >30% improvement in TSS and >75% reduction from baseline in tissue eosinophils) 
versus 5% of placebo-treated subjects (p<0.0001).  
Approximately 40% of subjects had concomitant EoE. In those subjects, a mean reduction of 
95% of eosinophils/hpf was observed in the esophageal biopsies of AK002-treated subjects 
versus no change on placebo. Also, 13 of 14 (93%) subjects with EoE on AK002 were histologic 
responders (defined by ≤6 eosinophils/hpf) versus 1 of 11 (9%) subjects with EoE on placebo. 
Dysphagia improved by 53% in AK002-treated subjects versus 17% in placebo-treated subjects.  
AK002 was well tolerated with IRR being the only AE that occurred more frequently in 
AK002-treated subjects than in placebo-treated subjects.  


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More than 90% of subjects in the Phase 2 study elected to continue into a long-term continuation 
study. In the long-term, open-label continuation 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 dose and second dose and, using this regimen, no IRR were reported for 
the first infusion of the continuation study. 
2.4 
Eosinophilic Gastrointestinal Disorders  
Eosinophilic esophagitis represents the most common type of eosinophilic gastrointestinal 
disorders (EGID) and is characterized by chronic inflammation due to patchy or diffuse 
infiltration of eosinophils into layers of the esophagus (Collins, 2018; Dellon, 2014). Diagnosis 
is made based on clinical presentation combined with increased tissue eosinophils in biopsy 
specimens from the esophagus, without any other cause for the eosinophilia. Clinical 
manifestations of the disease include dysphagia, food impaction, refractory reflux, abdominal 
discomfort, nausea, and vomiting/regurgitation. The symptoms are believed to be due to the 
release of inflammatory mediators from activated eosinophils and possibly mast cells, resulting 
in inflammatory changes including strictures (Abonia, 2010; Furuta, 2014). Active EoE has been 
defined by the presence of intramucosal eosinophilia with a peak count of ≥15 eosinophils/hpf 
(Dellon, 2014).  
Chronic inflammation and progressive fibrosis in EoE lead to narrow caliber esophagus and 
formation of strictures. At the time of diagnosis, up to 67% of adults and 16% of children already 
have fibrostenotic disease (Warners, 2018). The pathogenesis of EoE is immune-mediated, 
triggered in response to food or environmental antigens. The initial Th2 inflammatory response 
with the release of various cytokines including IL-4, IL-5, IL-13, and Eotaxin-3 leads to 
trafficking of eosinophils to the esophageal mucosa, which is normally devoid of any eosinophils 
(Collins, 2018). The inflammatory infiltrate in EoE is most notable for the presence of 
eosinophils and mast cells, which appear to be the primary drivers of tissue damage and eventual 
development of fibrosis (Abonia, 2010; Collins, 2018).  
Eosinophilic esophagitis is currently estimated to affect 4 out of 10,000 persons in the United 
States (Dellon, 2014; Jensen, 2016). The incidence and prevalence of EoE is rapidly increasing, 
though whether this represents a true increase in incidence or is due to increased awareness and 
recent consensus on guidelines for diagnosis is unknown (Syed, 2012). Patients may also have 
concomitant atopic diseases like food allergy, asthma, and atopic dermatitis, which further 
impact patients’ quality of life and contribute to health care costs. Also, 8%–10% of patients 
with EoE may develop other eosinophilic gastrointestinal diseases like EG and/or EoD 
(Jensen, 2016).  


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There are no FDA-approved treatments for EoE. Current therapies and disease management 
include dietary elimination, proton pump inhibitors (PPI), and topical or systemic steroids. 
Partial benefit has been observed with dietary elimination and PPI, but 40%–50% of patients 
are refractory to these measures (Arias, 2014; Dellon, 2014; Katz, 2013; Molina-Infante, 2016). 
In addition, responders to dietary elimination have demonstrated poor long-term adherence 
(Lucendo, 2013; Philpott, 2016; Reed, 2017). Corticosteroids, topical or systemic, have been 
shown to provide symptom relief but are not appropriate for long-term treatment due to 
numerous side effects and associated risks. Both topical (swallowed) and systemic 
corticosteroids have been shown to cause infection, adrenal insufficiency, bone demineralization, 
diminished growth, and cataracts (Furuta, 2015; Konikoff, 2006). Occasionally, in treatment-
refractory cases, immunomodulatory biologics are attempted, but the role of biologics in 
treatment algorithms remains to be defined (Assa’ad, 2011; Clayton, 2014; Hirano, 2019; 
Hirano, 2017; Markowitz, 2018; Rothenberg, 2014; Spergel, 2012; Straumann, 2010). Given the 
chronic and progressive nature of the disease and lack of approved therapies, better treatment 
options are clearly needed to manage EoE. 
AK002 was tested in a randomized, double-blind, placebo-controlled, Phase 2 study in 
65 subjects with EG and/or EoD (previously referred to as EGE). Subjects were randomized 
1:1:1 to 1 of 3 dose groups: placebo, low dose regimen (4 monthly doses of AK002 at 0.3, 1, 
1, and 1 mg/kg), or high dose regimen (4 monthly doses of AK002 at 0.3, 1, 3, and 3 mg/kg). 
All primary and secondary endpoints were met. There was a 97% and 92% mean reduction in 
eosinophils in the stomach and duodenum at the high dose and low dose regimens, respectively, 
versus a 10% increase for placebo (p<0.0001). The reduction of eosinophils was associated with 
improvement in TSS of 58% in the high dose group, 49% in the low dose group, versus 24% 
reduction in the placebo-treated group (p=0.0012).  
Approximately 40% of subjects with EG and/or EoD in the Phase 2 study had concomitant EoE, 
and these subjects had a 95% reduction in mean eosinophil count in esophageal biopsies 
associated with a substantial improvement in dysphagia on AK002 (53% reduction in dysphagia 
on AK002 versus 17% on placebo). In addition, 13 of the 14 EoE subjects receiving AK002 were 
histological responders with ≤6 eosinophils/hpf at Week 14. 
By markedly reducing eosinophil numbers and inhibiting mast cell activity, AK002 may be 
useful in the treatment of patients with EoE. This Phase 2/3 study will evaluate the safety, 
tolerability, and clinical benefit of repeat doses of AK002 in adult and adolescent subjects with 
symptomatic EoE. Assessment of clinical benefit will include symptomatic, endoscopic, and 
histological improvement in the disease. 


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 3 6  of 1 4 0  
C o nfi de nti al  
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 s u bjects wit h I S M, c hr o nic
urticaria, se v er e A C , mast cell gastritis, a n d E G a n d/ or E o D, t he pr o p ose d A K 0 0 2 d ose re gi me n
of 6 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 eit her 1 m g/ k g or 3 m g/ k g a d mi nistere d
e ver y 4 w ee ks f or 5 s u bse q ue nt i nf usi o ns.
S u bjects w h o c o m plete t he d o u ble- bli n d, pla ce b o -c o ntr olle d treat me nt (all 6 d oses of place b o or 
A K 0 0 2) a n d t he Da y 1 6 9 visit ma y ha ve t he o pti o n t o recei ve 6 d os es of o p e n-la bel A K 0 0 2 
t hr o u g h partici pati o n i n t he O pe n- L a bel E xte n d e d D osi n g ( O L E) Peri o d of t he st u d y.  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
C CI
C CI
C CI
C CI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 37 of 140 
Confidential 
Twelve to 24 hours prior to the first infusion of study drug, subjects will self-administer oral 
prednisone premedication (40 mg if body weight is <40 kg, 60 mg if body weight is ≥40 kg and 
<60 kg, or 80 mg if body weight is ≥60 kg).  
The proposed dose regimen in this EoE study is 6 doses of AK002 or placebo: 1 mg/kg for the 
first infusion, followed by either 1 mg/kg or 3 mg/kg administered every 4 weeks for 
5 subsequent infusions (with the option to receive 6 additional infusions of open-label AK002 
through participation in the OLE period). 
4.
Study Objectives
4.1 
Primary Efficacy Objective 
To evaluate the clinical benefit of AK002 in adult and adolescent subjects with active EoE when 
compared to placebo, efficacy endpoints will be co-primary: 
1)
The proportion of subjects who achieve a peak esophageal intraepithelial count of
≤6 eosinophils/hpf at Week 24.
2)
Mean change in Dysphagia Symptom Questionnaire (DSQ) score from Baseline to
Weeks 23–24.
4.2 
Secondary Objectives 
To further evaluate the clinical benefit of AK002 in adult and adolescent subjects with active 
EoE when compared to placebo as measured by: 
1)
Percent change in peak esophageal intraepithelial eosinophil count at Week 24.
2)
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of
≤1 eosinophil/hpf at Week 24.
3)
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of
<15 eosinophils/hpf at Week 24.
4)
Proportion of treatment responders when a responder is a subject achieving >30% reduction
in symptoms (DSQ) at Weeks 23–24 and achieving a peak intraepithelial eosinophilic count
of ≤6 eosinophils/hpf at Week 24.
5)
Proportion of subjects with >50% reduction in DSQ score from Baseline to Weeks 23–24.
6)
Percent change in DSQ score from Baseline to Weeks 23–24.
7)
Change in biweekly mean DSQ over time.
8)
Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) from Baseline to
Week 24.


Protocol AK002-014 
Amendment 6 
Date: 2FW 2021 
Allakos Inc. 
Page 38 of 140 
Confidential 
4.3 
Exploratory Objectives 
The exploratory objectives are to further evaluate the effect of AK002 in adult and adolescent 
subjects with active EoE by comparing AK002 to placebo for the following parameters:  
1)
Change in 
 from Baseline to Week 24.
2)
Change in 
 from Baseline to Week 24.
3)
Change in 
 from Baseline to Week 24.
4.4 
Safety Objectives 
To evaluate the safety and tolerability of AK002 in adult and adolescent subjects with active EoE 
by determining AE incidence and severity, study withdrawals due to AE, changes in vital signs 
and laboratory tests including immunogenicity, changes in concomitant medications beginning 
on or after the first infusion of study drug, and other safety parameters. 
4.5 
Target of Estimation 
The estimand (target of estimation) for the study is: 
In patients with active EoE, what is the between group (AK002 vs. Placebo) difference 
in the proportion of tissue eosinophil responders at Week 24, and between group 
difference in DSQ from baseline to Weeks 23–24 as measured by the patient-reported 
outcome (PRO) Dysphagia Symptom Questionnaire. 
The sections below describe the attributes of the estimand consistent with the ICH E9 Addendum 
(FDA, 2021). 
4.5.1 
Population Targeted by the Scientific Question 
The population targeted by the scientific question is defined by the inclusion and exclusion 
criteria as part of the study protocol. Patients must have a clinical diagnosis of active EoE. 
4.5.2 
Variables of Interest (or Endpoint) Required to Address the Scientific Question 
The co-primary endpoints to be obtained for each subject in this study to address the scientific 
question are Tissue Eosinophil Responders at Week 24 and change in DSQ from Baseline to 
Weeks 23–24 as measured by the PRO questionnaire. 
4.5.3 
Treatment 
AK002 or placebo administered to subjects on Days 1, 29, 57, 85, 113, and 141. 
CCI
CCI
CCI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 39 of 140 
Confidential 
4.5.4 
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.
•
Any therapeutic EGD (defined as dilatation or other intervention for a narrowing or
stricture of the esophagus) at any point during the study through Week 24.
Intercurrent events are described above, and further clarification and handling of ICE including 
prohibited/restricted medications are detailed in the Statistical Analysis Plan (SAP).  
4.5.5 
Strategy for Handling Intercurrent Events  
For analysis of the study product, the estimand tissue eosinophil values and DSQ scores will be 
counted as non-responders for binary variables and set to missing for continuous outcomes from 
the point when an ICE occurs. An appropriate method for handling missing data through 
statistical modeling (e.g., multiple imputation [MI]) will be used. The estimand will provide an 
answer to the question that is crucial to individual subjects: 
If I take this study medication as part of my treatment regimen, without adding 
any further medications that may impact the underlying disease or exit the study 
prematurely, what improvements in histology and PRO symptoms might be 
anticipated after 24 weeks? 
4.5.6 
Summary Measure of the Estimand 
•
Percent (and 95% confidence interval [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 DSQ of
Weeks 23-24 and the between treatment difference in the AK002 and placebo treatment
groups LSM.
5.
Study Design
5.1 
Study Overview 
This is a Phase 2/3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the safety, tolerability, and clinical benefit of AK002 in adult and adolescent subjects with active 
EoE. Subjects enrolled in the study will receive 6 infusions of placebo or AK002 administered 
every 4 weeks and will be followed for 8 weeks after the last dose. 


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 40 of 140 
Confidential 
Subjects who successfully complete the double-blind, placebo-controlled treatment period 
(including the Day 169 visit) may have the option to receive 6 doses of open-label AK002 
through participation in the optional Open-Label Extended Dosing (OLE) Period of the study 
and will be followed for 8 weeks after the last dose. 
Subjects will be consented and then screened for 14 to 60 days (or a maximum of 35 days after 
the Screening EGD, whichever is shorter). During the screening period, a baseline, stable 
regimen of PPI and/or dietary intake will be established, if needed, and baseline disease activity 
data will be collected. Swallowed topical corticosteroids and systemic corticosteroids will not be 
allowed. Subjects who meet eligibility criteria can be enrolled into the study. Subjects who do 
not meet all eligibility criteria at screening, or who qualify at screening but are not enrolled, may 
be assigned a new patient identification number and rescreened once. Subjects rescreened within 
30 days of signing the initial informed consent form (ICF) will not need to reconsent if no 
changes have been made to the ICF. 
Prior to the first dose of study drug (12–24 hours prior to the infusion), subjects will be 
premedicated with oral prednisone (40 mg if body weight is <40 kg, 60 mg if body weight is 
≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg). Subjects will self-administer oral 
prednisone 12–24 hours prior to the start of the first infusion only.  
Eligible subjects will receive the first dose of placebo or AK002 (1 mg/kg) on Day 1 and will 
remain confined to the clinic for at least 1 hour of observation (or greater, as per Investigator 
discretion) following the end of the infusion. On Day 29, subjects will receive a second dose of 
placebo or AK002 (1 mg/kg or 3 mg/kg) and will remain confined to the clinic for at least 1 hour 
of observation (or greater, as per Investigator discretion) following the end of the infusion. If the 
study drug is well tolerated (no stopping rules met), subjects will continue to receive doses of 
placebo, 1 mg/kg AK002, or 3 mg/kg AK002 on Days 57, 85, 113, and 141 for a total of 6 doses. 
Subjects will remain at the site for at least 1 hour of observation (or longer, as per the 
Investigator’s discretion) after each dose. In the event of an IRR, the subject may require 
prolonged observation (>1 hour or until the symptoms resolve), as per the Investigator’s 
discretion. Subjects will also be instructed to immediately contact the study doctor if any 
reactions occur after discharge. 
During the treatment period, subjects will return to the clinic for study visits as described in the 
Schedule of Events (Table 1). After completion of the Day 169 visit, the Investigator will 
evaluate whether the subject is eligible for the OLE period. Only subjects who successfully 
complete the double-blind treatment period (including the Day 169 visit) will have the option to 
participate in the OLE period, provided all eligibility criteria for the OLE period are satisfied.  


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 41 of 140 
Confidential 
Subjects who are not eligible for (or who choose not to participate in) the OLE period will 
complete the Follow-Up Period, including the Day 169 (±7) visit (4 weeks after the last dose) 
and the Day 197 (±7) visit (8 weeks after the last dose) per the Schedule of Events (Table 1). 
Eligible subjects who choose to participate in the OLE period will begin following the OLE 
Schedule of Events (Table 5) and will receive the first dose of open-label AK002 approximately 
1 week after Day 169 (on Day 176 ±3 days). 
If absolute lymphocyte and/or eosinophil counts have not recovered (to normal range or baseline 
levels) by the Day 197 visit (or the Day 372 visit for subjects participating in the OLE period), 
extended follow-up visits are required approximately every 4 weeks to monitor blood counts 
until they recover. 
The study design is summarized as follows: 
•
A 14 to 60-day (or a maximum of 35 days after the Screening EGD, whichever is shorter)
screening period with baseline evaluations for eligibility, including baseline disease activity
(by daily PRO questionnaire) and esophago-gastro-duodenoscopy (EGD) with biopsy.
•
Prior to the first dose of study drug (12–24 hours prior to the infusion), subjects will be
premedicated with oral prednisone (40 mg if body weight is <40 kg, 60 mg if body weight
is ≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg).
•
Eligible subjects will receive 6 doses of AK002 (or placebo) by IV infusion on Days 1,
29 (±3), 57 (±3), 85 (±3), 113 (±3), and 141 (±3). Subjects will self-administer prednisone
12–24 hours prior to the start of the first infusion only.
•
Subjects will remain at the site for at least 1 hour of observation after each dose. In the
event of an IRR, the subject may require prolonged observation (>1 hour or until the
symptoms resolve), as per Investigator discretion. Subjects will also be instructed to
immediately contact the study doctor if any reactions occur after discharge.
•
A repeat EGD with biopsy will be performed on Day 169 (±3) or 28 (±3) days after last
dose if subject is terminated early between Day 29 and Day 169 study visits.
•
After completion of the Day 169 visit, the Investigator will evaluate whether the subject is
eligible for the OLE period.
•
Subjects who are eligible and choose to participate in the OLE period will begin following
the OLE Schedule of Events (Table 5) on Day 176 (±3). The OLE period includes 6 doses
of open-label AK002 administered on Days 176 (±3), 204 (±3), 232 (±3), 260 (±3), 288
(±3), and 316 (±3) and post-treatment follow-up visits on Day 344 (±7) and Day 372 (±7).


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 42 of 140 
Confidential 
•
Subjects who are not eligible for (or who choose not to participate in) the OLE period will
be followed for approximately 8 weeks after the last dose per the Schedule of Events
(Table 1). The Follow-Up Period includes the Day 169 (±7) visit (4 weeks after the last
dose) and the Day 197 (±7) visit (8 weeks after the last dose).
•
If absolute lymphocyte and/or eosinophil counts have not recovered by the Day 197 visit
(or the Day 372 visit for subjects participating in the OLE period), subjects will return
approximately every 28 days for extended follow-up until counts have recovered.
•
Total study duration is approximately 33–36 weeks or 58–61 weeks for subjects
participating in the OLE period, though the study duration could be extended for
monitoring absolute lymphocyte and/or eosinophil counts (as described above).
5.2 
Schedule of Events 
The schedule of procedures and assessments (excluding the OLE period) is depicted in Table 1. 
The OLE schedule of procedures and assessments is depicted in Table 5 (Section 19.12.5).  


P r ot oc ol A K 0 0 2-0 1 4  
A me n d me nt 6 
Date : 2 8 Oct  2 0 2 1  
Alla k os I nc.  
Pa ge 4 3  of 1 4 0  
C o nfi de nti al  
T a ble 1  
A K 0 0 2- 0 1 4 Sc he d ule of E ve nts 
Descri pti o n  
B aseli ne/  
Scree ni n g 2 
(1 4 – 6 0  d a ys ) 
D ose 1  
D a y 1 2 
D a y 8  
( ± 1 d a y) 
D a y 1 5 
( ± 2 d a ys) 
D ose 2  
D a y 2 9  
( ± 3 d a ys)3 5 
D ose 3  
D a y 5 7  
( ± 3 d a ys)3 5 
D ose 4  
D a y 8 5  
( ± 3 d a ys)3 5 
D ose 5  
D a y 1 1 3  
( ± 3 da ys)3 5 
D ose 6  
D a y 1 4 1  
( ± 3 da ys)3 5 
D a y 1 6 9  
( ± 3 da ys) 3 5 
( or E T3 2) 
E O S  
D a y 1 9 7  
( ± 7 da ys) 
E xte n de d 
F oll o w -U p 3 3  
I nf or me d c o nse nt 
X 
De m o gra p hics a n d Me dical Hist or y  
X  
St o ol f or O va a n d Parasite 3 
X 
e P R O Acti vati o n a n d Trai ni n g 4 
X 
D S Q P R O 5 
D aily fr o m Scree ni n g t hr o u g h E n d of St u dy ( or E T) ----------------------------------------------------------------------------------------------------> 
 
X 
X 
X 
E G/ E o D P R O Q uesti o n naire 7 
X 
 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
Baseli ne Diet Assess me nt 9 
X  
Baseli ne Diet C o m plia nce 9 
X 1 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
B o d y Wei g ht a n d Hei g ht 1 0 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
Vital Si g ns 1 1 
X 
X 1 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
1 0 or 1 2 -Lea d E C G 1 2 
X  
C o m plete P h ysical E xa mi nati o n 1 3 
X 
E G D wit h Bi o ps y C ollecti o n 1 4 
X 
X 
E R E F S Sc ori n g d uri n g E G D 1 5 
X  
X  
Bl o o d f or Ser ol o g y 1 6, 1 7 
X 
Bl o o d f or Ser u m h C G a n d F S H 1 6, 1 8 
X 
Bl o o d f or T otal Ser u m I g E 1 6, 1 9 
X 1 
X 1 
X 
Bl o o d f or C B C w/ Differe ntial 1 6, 2 0 
X  
X 1 
X  
X  
X 1 
X 1 
X 1 
X 1 
X 1 
X  
X  
X  
Bl o o d f or C he mistr y 1 6, 2 1 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
Bl o o d f or P K 1 6, 2 2 
X 1 
X 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
Bl o o d f or A D A 1 6, 2 3 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X  
Bl o o d f or E x pl orat or y A nal ysis 1 6, 2 4 
X  
X  
X  
X  
Bl o o d f or E x pl orat or y Safet y 1 6, 2 5 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
C CI
C CI


P r ot oc ol A K 0 0 2-0 1 4  
A me n d me nt 6 
Date : 2 8 Oct  2 0 2 1  
Alla k os I nc.  
Pa ge 4 4  of 1 4 0  
C o nfi de nti al  
T a ble 1   
A K 0 0 2- 0 1 4 Sc he d ule of E ve nts c o nt.  
Descri pti o n  
B aseli ne/  
Scree ni n g 2 
(1 4 -6 0 d a ys ) 
D ose 1  
D a y 1 2 
D a y 8  
( ± 1 d a y) 
D a y 1 5 
( ± 2 d a ys) 
D ose 2  
D a y 2 9  
( ± 3 d a ys)3 5 
D ose 3  
D a y 5 7  
( ± 3 d a ys)3 5 
D ose 4  
D a y 8 5  
( ± 3 d a ys)3 5 
D ose 5  
D a y 1 1 3  
( ± 3 da ys)3 5 
D ose 6  
D a y 1 4 1  
( ± 3 da ys)3 5 
D a y 1 6 9  
( ± 3 da ys) 3 5 
( or E T3 2) 
E O S  
D a y 1 9 7  
( ± 7 da ys) 
E xte n de d 
F oll o w -U p 3 3  
Uri ne f or Uri nal ysis 1 6, 2 6 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
Eli gi bilit y Assess me nt  
X  
X 1 
Pre me dicati o n – pre d nis o ne 2 8 
X 1 
Uri ne Di pstic k Pre g na nc y Test 1 6, 2 7 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
Access I R T – I P Kit Assi g n me nt 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
St u d y Dr u g A d mi nistrati o n 2 9 
X 
X 
X 
X  
X 
X 
P ost -D ose O bser vati o n 2 9 
X 
X 
X 
X  
X 
X 
S y m pt o m -Directe d P h ysical E xa m 3 0 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
Pri or a n d  C o nc o mita nt Me dicati o ns  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 3 4 
X  
A d verse E ve nts 3 1 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
O pe n -La bel E xte n de d D osi n g 3 4 
X 3 4 
X 3 4  – Da y 1 9 7 visit 
d oes  n ot a p pl y t o 
s u bjects i n O L E peri o d  
A D A:  A nti - dr u g A nti b o d y  
E T:  
Earl y Ter mi nati o n  
F S H:  F ollicle -Sti m ulati n g H or m o ne  
I P: I n vesti gati o nal Pr o d uct 
C B C:  C o m plete Bl o o d C o u nt  
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   
P K: P har mac o ki netics  
D S Q:  D ys p ha gia S y m pt o m Q uesti o n naire  
E G D:  Es o p ha g o -gastr o -d u o de n osc o p y  
I R T: I nteracti ve Res p o nse Tec h n ol o g y 
T a ble 1 N otes  
1)
Refer t o assess me nt f o ot n ote f or s pecific ti me p oi nts (e. g., pre d ose, d uri n g i nf usi o n, p ost d ose) t o c o n d uct t he assess me nt o n  d osi n g da ys.
2)
T he s cree ni n g peri o d ( Baseli ne ) assess me nts ca n be c o n d ucte d o ver m ulti ple da ys wit hi n t he scree ni n g peri o d. T he scree ni n g peri o d m ust be a mi ni m u m of 1 4 da ys ( 2 wee ks)
a n d n o l o n ger t ha n 6 0  da ys ( or a ma xi m u m of 3 5 da ys after t he Scree ni n g E G D, w hic he ver is s h orter). Da y 1 ca n be gi n as s o o n as eli gi bilit y criteria are met.
3)
Fecal c ollecti o n kits f or O va a n d Parasite will be pr o vi de d t o s u bjects at t he ti me of c o nse nt. St o ol sa m ple s h o ul d be ret ur ne d t o t he cli nical site wit hi n 2 4 h o urs of c ollecti o n.
4)
At t he ti me of c o nse nt, t he St u d y C o or di nat or will acti vate all e P R O q uesti o n naires i n E D C, pr o vi de t he s u bject wit h a u ni q ue  user na me a n d pass w or d, trai n t he s u bject o n
dail y D S Q e P R O c o m pleti o n a n d c o m plia nce, a n d e ns ure t he s u bject is a ble t o c o m plete t he 
 q uesti o n naire o n t heir pers o nal electr o nic de vice w hile o n site.
5)
S u bjects s h o ul d c o m plete t he D S Q dail y after t he last meal of t he da y. If Q uesti o n 1 is a ns were d “ N o,” t he s u bject s h o ul d a ns wer t he S oli d F o o d Q uesti o n ( A p pe n di x 2 ) after
t he D S Q is c o m plete d a n d s u b mitte d. T he site is res p o nsi ble f or m o nit ori n g c o m plia nce t hr o u g h o ut t he d urati o n of t he st u d y a n d disc ussi n g c o m plia nce d uri n g st u d y visits.
C CI


P r ot oc ol A K 0 0 2-0 1 4  
A me n d me nt 6 
Date : 2 8 Oct  2 0 2 1  
Alla k os I nc.  
Pa ge 4 5  of 1 4 0  
C o nfi de nti al  
T a ble  1 N otes c o nt.  
6)
O n Da y -2 ( 2 da ys bef ore Da y 1), o n Da y 1 5 (a p pr o xi matel y 2 wee ks after t he first d ose), a n d o n Da y 2 9 (a p pr o xi matel y 4 wee ks after t he first d ose), s u bjects will
self-a d mi nister t he 
 after t he y s u b mit t he D S Q (a n d S oli d F o o d Q uesti o n, if a p plica ble). O n Da y 1 5 a n d
Da y  2 9, s u bjects will als o self -a d mi nister t he 
 after t he D S Q, S oli d F o o d Q uesti o n (if a p plica ble), a nd 
7)  
D uri n g t he scree ni n g peri o d o nl y, s u bjects s h o ul d c o m plete t he E G/ E o D P R O q uesti o n naire dail y after c o m pleti o n of t he D S Q (a n d S oli d F o o d Q uesti o n, if a p plica ble).
8)
T he 
 electr o nic q uesti o n naire s h o ul d be t he first assess me nt c o m plete d b y t he s u bject at t he be gi n ni n g of t he st u d y visit pri or t o all ot her st u d y visit assess me nts.
9)
A baseli ne diet assess me nt will be perf or me d usi n g t he sta n dar dize d q uesti o ns i n A p pe n di x 7 . Eati n g patter ns, f o o d a v oi da nce be ha viors, a n d aller gies will be ca pt ure d.
Per  I ncl usi o n Criteria # 7 , s u bjects s h o ul d mai ntai n baseli ne diet t hr o u g h o ut t he st u d y. Diet c o m plia nce will be disc usse d d uri n g st u d y visits, a n d a n y varia nce will be
d oc u me nte d.
1 0)
Hei g ht (i n c m) a n d wei g ht (i n k g) will be meas ure d at scree ni n g. Wei g ht will als o be meas ure d pre d ose o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, 1 4 1, a n d o n Da ys 1 6 9 a n d 1 9 7 ( or E T).
1 1)
Vital si g ns will be meas ure d at b aseli ne a n d o n Da ys 1, 1 5, 2 9, 5 7, 8 5, 1 1 3, 1 4 1, 1 6 9, a n d 1 9 7 ( or 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), vital si g ns will be
meas ure d pre d ose, 1 5 mi n utes ( ± 5 mi n utes) after i nf usi o n start, i m me diatel y p ost d ose ( wit hi n 5 mi n utes after i nf usi o n e n d), a n d 1 h o ur ( ± 5 mi n utes) p ost d ose. S u bject s h o ul d
be at rest f or ≥5 mi n utes bef ore vital si g ns (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) are meas ure d.
1 2)
Baseli ne E C G s h o ul d be perf or me d after t he s u bject has bee n i n t he s u pi ne p ositi o n f or ≥5 mi n utes a n d,  if d o ne o n t he sa me da y as bl o o d c ollecti o n, d o bef ore bl o o d is dra w n.
1 3)
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.
1 4)
A n E G D wit h bi o ps y c ollecti o n will be perf or me d d uri n g scree ni n g a n d at Da y 1 6 9 ( ± 3 da ys). E G D bi o psies will be c ollecte d, pr ocesse d, a n d s hi p pe d i n acc or da nce wit h
A p pe n di x 9 , t he la b ma n ual, a n d t he hist ol o g y ma n ual. Da y 1 6 9 bi o ps y res ults will be bli n de d. If E T  occ urs  after Da y 2 9 a n d  bef ore Da y 1 6 9, a n E G D wit h bi o ps y c ollecti o n
s h o ul d be d o ne 2 8 (± 3) da ys after t he last d ose (as part of t he  E T visit , see Ta ble Note 3 2 ). If resc ue t hera p y is re q uire d, a n E G D ( bi o ps y a n d E R E F S) m ust be d o ne pri or t o
i nitiati o n of resc ue me dicati o n or at t he ti me of e mer ge nc y dilati o n (i nstea d of at Da y 1 6 9).
1 5)  D uri n g t he Scree ni n g  E G D  a n d Da y 1 6 9 E G D, se verit y will be e val uate d usi n g t he E o E Refere nce Sc ore f or E n d osc o pic A b n or malities per t he st u d y hist ol o g y ma n ual.
1 6)
Please see t he st u d y ce ntral la b orat or y ma n ual  f or c ollecti o n, pr ocessi n g, a n d s hi p me nt i nstr ucti o ns. If p ossi ble, sa m ples s h o ul d be s hi p pe d o n t he sa me da y as c ollecti o n.
1 7)
Bl o o d f or ser ol o g y ( He patitis B s urface a nti ge n, He patitis C a nti b o d y, He patitis B c ore a nti b o d y, a n d HI V) will be o btai ne d d u ri n g scree ni n g.
1 8)
F or fe male s u bjects, bl o o d will be o btai ne d d uri n g scree ni n g t o test f or h C G ( pre g na nc y) a n d F S H ( p ost -me n o pa usal stat us).
1 9)
Bl o o d f or t otal ser u m I g E will be o btai ne d o n Da ys 1 ( pre d ose), 8 5 ( pre d ose), a n d 1 6 9 or E T, if s u bject earl y  ter mi nates bef ore Da y 1 6 9.
2 0)
Bl o o d f or C B C wit h differe ntial will be o btai ne d at all st u d y visits. O n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, a n d 1 4 1, bl o o d will be dra w n t wice ( pre d ose a n d 1 -h o ur p ost d ose). F or e ver y
C B C wit h differe ntial bl o o d c ollecti o n e xce pt scre e ni n g a n d Da y 1 ( pre d ose), t he bl o o d c o u nt res ults will be bli n de d t o t he S p o ns or a n d t he site. T he safet y m o nit or ma y
re q uest a n u nsc he d ule d C B C wit h differe ntial. Bl o o d c o u nts fr o m Da y 1 9 7 will be use d t o deter mi ne if e xte n de d f oll o w-u p is nee de d.
2 1)
Bl o o d f or c he mistr y will be o btai ne d d uri n g scree ni n g, pre d ose o n d osi n g da ys ( Da ys 1, 2 9, 5 7, 8 5, 1 1 3, 1 4 1), a n d o n Da ys 1 6 9  a n d 1 9 7 ( or E T).
C CI
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C CI
C CI


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Table 1 Notes cont. 
22)
Blood for PK will be obtained on Days 1, 8, 15, 29, 57, 85, 113, 141, 169, and 197 (or ET). Blood will be drawn predose on Days 1, 29, 57, 85, 113, and 141.
23)
Blood for ADA will be obtained predose on Days 1, 29, 57, 85, 113, and 141, on Day 197 (or ET), and in the event of a suspected immunogenicity-related AE.
24)
Blood for exploratory analysis will be obtained during screening and on Days 15, 169, and 197 (or ET).
25)
If an infusion-related reaction results in infusion interruption or cessation, blood for exploratory safety analyses will be obtained within 1–2 hours of symptom onset.
26)
Urine for standard urinalysis will be obtained during screening, as needed (if warranted in the opinion of the Investigator or Subinvestigator), and on Day 197 (or ET).
27)
For females of childbearing potential, urine for dipstick pregnancy test will be collected, tested, and results confirmed predose on Days 1, 29, 57, 85, 113, and 141.
28)
The day before the first dose (12–24 hours prior to the planned infusion start time), eligible subjects will self-administer oral prednisone premedication based on body weight.
29)
Study drug (or placebo) will be administered as a single peripheral IV infusion over ≥4 hours on Day 1, over ≥3 hours on Day 29, and over ≥2 hours for subsequent infusions
(Days 57, 85, 113, and 141). Refer to the Pharmacy Manual for detailed instructions on preparation, administration, and infusion rate schedule requirements.
30)
If a new or worsening symptom (or clinically significant finding) is observed or reported, the Investigator or designee will perform a symptom-directed physical examination.
Symptom-directed physical examinations will be performed as needed and may be performed predose, during infusion, and/or postdose (including for possible IRRs).
31)
All AE, including Adverse Events of Special Interest (AESI) and SAE, will be captured beginning from the start of the first infusion. Serious adverse events occurring
between the time of consent and the start of the first study drug infusion will be reported only if they are assessed to be related to study procedures. For subjects participating
in the OLE period, AE will be assessed and recorded in the CRF of the AK002-014 treatment period database up until the start of the first open-label infusion during the Day
176 visit and recorded in the CRF of the AK002-014 OLE period database beginning from the start of the first open-label infusion during the Day 176 visit.
32)
ET visits should be conducted 28 (±3) days after the last dose of study drug or prior to this, if necessary, to ensure compliance with the visit. If a subject discontinues the
study >28 days after the last dose of study drug, the ET visit should be conducted as soon as possible. If the subject is terminated after Day 29 and before Day 169, the ET
visit will be performed 28 (±3) days after last dose and the ET visit will follow the Day 169 assessment schedule (including EGD with biopsy collection). If the subject is not
participating in the OLE period and the ET visit occurs after Day 169, the Day 197 assessment schedule should be followed for the ET visit. See Table 5 OLE Period
Schedule of Events for OLE period ET after Day 176.
33)
If absolute lymphocyte and/or eosinophil counts do not recover (to normal range or baseline levels) by Day 197 (or ET), extended follow-up visits are required every
28 (±3) days) to monitor blood counts until they recover. Extended follow-up visits consist of blood collection for CBC with differential and collection of AESI and SAE.
34)
After completion of the Day 169 visit, the Investigator will evaluate whether the subject is eligible for the OLE period. If the subject is eligible, the subject will be given the
option to participate in the OLE period beginning approximately 1 week after the Day 169 visit. Approximately 1 week after the Day 169 visit (on Day 176 ±3 days), eligible
subjects that choose to participate in the OLE period will begin following the OLE Schedule of Events (Table 5) and will receive the first open-label AK002 infusion. For
subjects participating in the OLE period, AE and concomitant medications should be collected and recorded in the AK002-014 Treatment Period database up until the start of
the first open-label infusion during the Day 176 visit. This includes prednisone premedication administered prior to the Day 176 visit of the OLE period, which should be
recorded in the Concomitant Medications CRF of both the AK002-014 treatment period database and the AK002-014 OLE period database.
35)
Sites should strive to conduct visits within a ±3 day window, but visits conducted within ±7 days are acceptable and are not considered deviations. Visits conducted ±4-7 days
from the target visit date should be minimized as much as possible. Any visit conducted outside of the ±3 day window should receive prior written approval from Allakos.


Protocol AK002-014 
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Allakos Inc. 
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6.
Criteria for Evaluation
6.1 
Safety Endpoints 
The safety and tolerability of AK002 will be assessed by determining the following: 
•
Physical examination (Section 11.3.5, 11.3.6)
•
Changes in vital signs (Section 11.3.4)
•
Changes in Hematology (Section 11.2.8 and Section 11.4.1)
•
Changes in Blood chemistry (Section 11.4.2)
•
Changes in Urinalysis (Section 11.4.3)
•
Anti-drug antibodies (Section 11.4.7)
•
Treatment-emergent adverse events (Section 13) include severity, withdrawals due to AE,
and other safety parameters.
•
Changes in concomitant medications beginning on or after the first infusion of study drug
(Section 11.3.1)
6.2 
Pharmacokinetic Endpoints 
Blood (serum) will be collected for assessment of AK002 concentrations using a validated 
enzyme-linked immunosorbent assay (ELISA) method. Pharmacokinetic blood samples will be 
obtained on Days 1, 8, 15, 29, 57, 85, 113, 141, 169, and 197 (or ET). On dosing days (Days 1, 
29, 57, 85, 113, and 141), blood for PK will be collected predose. 
Blood (serum) will be collected for assessment of AK002 ADA using a validated assay method. 
ADA blood samples will be obtained predose on Days 1, 29, 57, 85, 113, and 141, on Day 197 
(or ET), and in the event of a suspected immunogenicity-related AE. 
6.3 
Efficacy Endpoints 
6.3.1 
Co-Primary Efficacy Endpoints 
1)
The proportion of subjects who achieve a peak esophageal intraepithelial count of
≤6 eosinophils/hpf at Week 24.
2)
Mean change in DSQ score from baseline to Weeks 23–24.
6.3.2 
Secondary Efficacy Endpoints 
To further evaluate the efficacy of AK002 in adult and adolescent subjects with active EoE when 
compared to placebo as measured by: 


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1)
Percent change in peak esophageal intraepithelial eosinophil count at Week 24.
2)
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of
 eosinophil/hpf at Week 24.
3)
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of
<15 eosinophils/hpf at Week 24.
4)
Proportion of treatment responders when a responder is a subject achieving >30% reduction
in symptoms (DSQ) at Weeks 23–24 and achieving a peak intraepithelial eosinophilic count
RIHRVLQRSKLOVKSI at Week 24.
5)
Proportion of subjects with >50% reduction in DSQ score from Baseline to Weeks 23–24.
6)
Percent change in DSQ score from Baseline to Weeks 23–24.
7)
Change in biweekly mean DSQ over time.
8)
Change in EoE Reference Score for Endoscopic Abnormalities from Baseline to Week 24.
6.4 
Exploratory Endpoints 
1)
Change in 
 from Baseline to Week 24.
2)
Change in 
 from Baseline to Week 24.
3)
Change in 
 from Baseline to Week 24.
7.
Subject Selection
7.1 
Number of Subjects 
Approximately 300 subjects with symptomatic EoE will be randomized 1:1:1 to receive 1 of 
3 dose regimens in a double-blind fashion: placebo; the low dose regimen (1 mg/kg AK002 
administered every 4 weeks for 6 doses); or the high dose regimen (1 mg/kg AK002 for the first 
dose followed by 3 mg/kg AK002 administered every 4 weeks for the 5 subsequent doses). 
Subjects who successfully complete the randomized, double-blind, placebo-controlled treatment 
period (including the Day 169 visit) may have the option to receive 6 doses of open-label AK002 
through participation in the OLE period of the study. 
7.2 
Study Population 
Male and female EoE subjectVDJHGDQG\HDUVZKRIXOILOOWKHHOLJLELOLW\FULWHULD
specified below.  
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7.3 
Inclusion Criteria 
Subjects with active EoE are eligible for enrollment into the study if all of the following criteria 
are met: 
1)
Male or female aged ≥12 and ≤80 years at the time of signing the ICF.
2)
Confirmed diagnosis of EoE and intraepithelial eosinophilic infiltration of
≥15 eosinophils/hpf in 1 hpf from a biopsy collected during the Screening EGD without any
other cause for the esophageal eosinophilia.
3)
Baseline DSQ (biweekly mean DSQ) score of ≥12 from the last 2 weeks of screening
(the 14 days prior to the first dose) per the validated algorithm in Appendix 11.
4)
History (by subject report) of an average of ≥2 episodes of dysphagia with intake of solid
foods per week during the 4 weeks prior to screening.
5)
Subjects must have failed or not be adequately controlled on standard of care treatments for
EoE symptoms, which could include PPI, systemic or topical corticosteroids, and/or diet,
among others.
6)
If on an allowed treatment for EoE (per Section 8.2), stable dose for at least 4 weeks prior
to screening and willingness to continue that dose for the study duration.
7)
If subject is on preexisting dietary restrictions, willingness to maintain dietary restrictions
throughout the study, as much as possible.
8)
Able and willing to comply with all study procedures.
9)
Female subjects 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 either agree to use dual methods of contraception, have a partner who
had a vasectomy, or agree to abstain from sexual activity from screening until the end of the
study, or for 120 days following the last dose of study drug, whichever is longer.
Non-vasectomized male subjects with female partners of childbearing potential must agree 
to either abstain from sexual activity or agree to use a highly effective method of 
contraception from screening until the end of the study or for 120 days following 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 at any time during study participation. 


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7.4 
Exclusion Criteria 
Subjects will be excluded from the study if they meet any of the following criteria: 
1)
Concomitant moderately or severely symptomatic EG and/or EoD*, defined as:
−
≥30 eosinophils/hpf in 5 hpf in the stomach (EG) and/or ≥30 eosinophils/hpf in 3 hpf in
the duodenum (EoD) without any other cause for eosinophilia as determined by central
histology assessment of biopsies collected during the Screening EGD.
and 
−
EG/EoD PRO Questionnaire weekly average single symptom score of ≥3 during the last
2 weeks of screening for 1 of the following symptoms: abdominal pain, nausea, and/or
diarrhea.
*
This exclusion criterion is only applicable to sites actively enrolling subjects in the
AK002-016 study. If a site is not actively screening and enrolling subjects in the
AK002-016 study, then this exclusion criterion is not applicable.
2)
Causes of esophageal eosinophilia other than EoE or one the following: hypereosinophilic
syndrome, eosinophilic granulomatosis with polyangiitis, or peripheral blood absolute
eosinophil count >1500 eosinophils/µL.
3)
History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal
surgery.
4)
Any esophageal stricture unable to be passed with a standard diagnostic 9 mm to 10 mm
upper endoscope or any critical esophageal stricture that requires dilation during screening.
5)
History of bleeding disorders or esophageal varices.
6)
History of malignancy, except carcinoma in situ, early stage prostate cancer, or
non-melanoma skin cancers. However, cancers that have been in remission for more than
5 years and are considered cured can be enrolled (with the exception of breast cancer).
All history of malignancy (including diagnosis, dates, and compliance with cancer
screening recommendations) must be documented and certified by the Investigator, along
with the statement that in their clinical judgment the tissue eosinophilia is attributable to
EGID, rather than recurrence of malignancy.
7)
Active Helicobacter pylori infection (as determined by central histology staining of the
biopsy collected during the Screening EGD), unless treated and confirmed to be negative
prior to randomization and symptoms remain consistent.


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8)
Positive Ova and Parasite test at screening, seropositive for Strongyloides stercoralis at
screening, and/or treatment for a clinically significant helminthic parasitic infection within
6 months of screening.
9)
Seropositive for HIV or hepatitis at screening, except for vaccinated subjects or subjects
with a history of hepatitis that has since resolved.
10) Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
11) Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy
within 4 weeks prior to screening.
12) Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks
prior to screening.
13) Use of any biologics or medications that may interfere with the study, such as
immunosuppressive or immunomodulatory drugs including azathioprine, JAK inhibitors,
6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor
(e.g., dupilumab), anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g., benralizumab),
anti-IL-13 (e.g., lebrikizumab), and anti-IgE (e.g., omalizumab), within 12 weeks prior to
screening.
14) Participation in a concurrent interventional study with the last intervention occurring within
30 days prior to administration of study drug or 90 days or 5 half-lives, whichever is longer,
for biologic products.
15) Vaccination with live attenuated vaccines ≤30 days prior to initiation of treatment in the
study, during the treatment period, or vaccination expected ≤5 half-lives (≤4 months)
following study drug administration (with the exception of a COVID-19 vaccine authorized
by the FDA or other applicable regulatory agency).
16) Treatment with chemotherapy or radiotherapy in the preceding 6 months.
17) Presence of abnormal laboratory values considered by the Investigator to be clinically
significant.
18) Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion
of the Investigator, would place the subject at increased risk.
19) Known history of alcohol, drug, or other substance abuse or dependence.
20) Women who are pregnant, breastfeeding, or planning to become pregnant while
participating in the study.
21) Any other reason that in the opinion of the Investigator or Medical Monitor makes the
subject unsuitable for enrollment.


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8.
Prior and Concurrent Medications
Prior and concomitant medications (which include both prescribed and over-the-counter
medications taken at any point beginning 30 days prior to the screening visit and until the end of
study participation) will be recorded in the electronic Case Report Forms (eCRF). For subjects
participating in the OLE period, concomitant medications should be recorded in the AK002-014
treatment period database up until the first open-label dose is administered during the Day 176
visit. This includes the prednisone premedication administered prior to the Day 176 visit in the
OLE period, which should be recorded in the Concomitant Medications CRF of both the
AK002-014 treatment period database and the AK002-014 OLE period database.
Subjects should be advised against taking any new medication or modifying the dose of existing 
medication, both prescribed and over the counter, without consulting the Investigator, unless the 
new medication or change in dose is required for emergency use. Immediately prior to the first 
infusion, study site personnel should ensure that the subject continues to meet the inclusion 
criteria and none of the exclusion criteria including no 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 also be documented. 
8.1 
Prohibited Medications  
Any biologics or medications that may interfere with the study, such as swallowed 
corticosteroids, systemic corticosteroids, and systemic immunosuppressive or 
immunomodulatory drugs (including azathioprine, JAK inhibitors, 6-mercaptopurine, 
methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor (e.g., dupilumab), anti-IL-5 
(e.g., mepolizumab), anti-IL-5 receptor (e.g,. benralizumab), anti-IL-13 (e.g., lebrikizumab), 
anti-IgE (e.g., omalizumab), are prohibited for the duration of study participation. 
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. Any medications used for the 
treatment of IRR are not considered deviations from the protocol. 
Subjects will be reminded to not take prohibited medications and to notify the site immediately if 
a prohibited medication is prescribed by another health care provider.  
If medically necessary, rescue medications (systemic and/or swallowed topical corticosteroids) 
or emergency esophageal dilation may be used as rescue therapy. Any subject requiring rescue 
therapy must have an EGD (with biopsy collection and EREFS scoring) done prior to initiation 


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of rescue medications (or at the time of emergency esophageal dilation). The EGD performed 
due to initiation of rescue therapy will be used in place of the EGD scheduled for Day 169 
(Week 24), and the subject will not have an EGD performed at the Day 169 (Week 24) visit. 
Subjects receiving rescue therapy should remain blinded, continue to receive study drug, and 
continue to comply with all study visits and assessments in accordance with the Schedule of 
Events (Table 1). 
8.2 
Allowed Medications 
Medications, other than those that are prohibited (Section 8.1), such as antihistamines, 
leukotriene antagonists, sodium cromolyn, inhaled corticosteroids, nasal corticosteroids, PPI, 
and/or diet therapy are allowed during the study, and unless required due to unforeseen medical 
necessity, doses and/or dietary modifications are to remain stable. Systemic or swallowed 
FRUWLFRVWHURLGVZLWKDGRVHRIPJGD\RISUHGQLVRQHRUHTXLYDOHQWDUHDFFHSWDEOHDVORQJDV
the dose remains stable throughout screening and during the study. All medication use will be 
documented in the eCRF. 
Allakos allows all types and formulations of vaccines (including live attenuated vaccines) that 
are authorized by the FDA (or other applicable regulatory authority) for the prevention of 
COVID-19. These may be administered before, during, or after the study, but should not be 
administered within 7 days prior to or within 7 days after the administration of study drug (so the 
relationship of temporally-associated AE may be more easily assessed). Any vaccine for 
COVID-19 that is administered during the study collection period for concomitant medications 
will be recorded in the CRF. Additionally, any AE occurring during the study AE collection 
period will be recorded in the CRF.  
There is no reason to believe there is any increased risk to a subject who receives both AK002 
and a vaccine for the prevention of COVID-19. In addition, there is no reason to believe AK002 
negatively impacts the efficacy of a vaccine for COVID-19. Allakos will continue to monitor 
subject safety on an ongoing basis, paying special attention to any subject who receives the 
vaccine. 
9.
Study Treatment
9.1 
Formulation of Test Product and Placebo 
AK002 is a humanized non-fucosylated IgG1 monoclonal antibody directed against Siglec-8. 
AK002 IV drug product is supplied as a sterile liquid in a single-use 10R glass vial with a fill 
volume of not less than 10 mL. The product is stored at 2°C to 8°C. The AK002 formulation is 
 
 pH 6.0, in sterile Water for Injection.  
CCI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 5 4  of 1 4 0  
C o nfi de nti al  
Place b o is s u p plie d as a sterile li q ui d i n a si n gle - 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. Place b o c o ntai ns 
 
, p H 6. 0, i n steril e Water f or I njecti o n.  
N ote :  A K 0 0 2 a n d place b o will be referre d t o as “st u d y dr u g.” 
9. 2  
St u d y Dr u g P ac k a gi n g a n d L a beli n g  
A K 0 0 2 dr u g pr o d uct is s u p plie d as a sterile li q ui d i n a si n gle- 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 o ate d r u b ber st o p p ers 
a n d seale d wit h al u mi n u m seals. Eac h vial will be la bele d wit h t he re q uire d i n vesti gati o nal use 
state me nt, 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 m e nt s u bject 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 n v esti gati o nal Pr o d uct (I P) D ose Calc ulati o n a n d 
Pre parati o n W or ks heet a n d mai ntai ne d wit h t he s o urce d oc u m e 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 oc u me ntati o n a n d a p pr o vals ha ve b ee n 
recei v e d b y t he S p o ns or, t he c o ntract h as bee n e xec ute d, a n d t he first scree ne d s u bject is e ntere d 
i nt o t he I nteracti ve Res p o nse Tec h n ol o g y (I R T) s yste m. S u bse q ue nt st u d y dr u g s hi p me nts will 
be tri g gere d a ut o maticall y base d o n pre d eter mi ne d s u p pl y le vels a n d e nr oll me nt acti vit y at 
t he site.  
9. 4  
St u d y Dr u g D os a ge/ D os a ge Re gi me n 
S u bjects will be ra n d o ml y assi g ne d t hr o u g h t he I R T s yste m t o d osi n g gr o u ps of 1 m g/ k g A K 0 0 2 
( 6 d oses at 1 m g/ k g), 3 m g/ k g A K 0 0 2 (first d ose at 1 m g/ k g a n d 5 s u bse q ue nt d oses at 3 m g/ k g), 
or place b o. St u d y dr u g vi al la bels will be bli n de d. T he e xact d ose will be calc ulate d pri or t o eac h 
i nf usi o n a n d base d o n s u bject’s wei g ht. St u d y dr u g will be ad 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). Eli gi ble s u bjects t hat c h o ose t o partici pate i n t he O L E 
p eri o d will recei ve o pe n -la bel A K 0 0 2 a d mi nistere d at 1 m g/ k g f or t he first O L E peri o d  i nf usi o n 
a n d eit her 1 m g/ k g or 3 m g/ k g f or t he s u bse q ue nt O L E peri o d  i nf usi o ns o n Da ys 1 7 6 ( ± 3), 
2 0 4 ( ± 3), 2 3 2 ( ± 3), 2 6 0 ( ± 3), 2 8 8 ( ± 3), a n d 3 1 6 ( ± 3). 
9. 5  
Pre p ar ati o n of St u d y Dr u g  
St u d y dr u g vial la bels will be bli n de d a n d t he st u d y p har macist ( or d esi g nee) will pre pare t he 
st u d y dr u g f or eac h i nf usi o n. T he desi g nate d st u d y p har macist will pre pare t he a p pr o priat e 
dil uti o n of A K 0 0 2 f or I V a d mi nistrati o n base d o n t he s u bject’s wei g ht o btai ne d t he da y 
of d osi n g.  
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Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 55 of 140 
Confidential 
Appropriate aseptic technique will be used, and the drug will be prepared according to the 
Pharmacy Manual for AK002-014. Please refer to the Pharmacy Manual for additional details 
and step-by-step instructions regarding study drug preparation. 
The infusion must be completed within 8 hours of preparation. 
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 placebo or AK002 at a dose of 1 mg/kg will be prepared according to 
the subject’s body weight and administered over ≥4 hours on Day 1. Subsequent infusions of 
placebo or AK002 at a dose of 1 mg/kg or 3 mg/kg will be prepared on Day 29 (±3), Day 57 
(±3), Day 85 (±3), Day 113 (±3), and Day 141 (±3). Depending on the subject’s tolerance of the 
first and subsequent infusions (and at the Investigator’s discretion), the second infusion can be 
given over ≥3 hours, and the subsequent 4 infusions can be given over ≥2 hours. If the infusion is 
slowed or interrupted, the infusion length may exceed 4 hours but must be completed within 
8 hours of preparation (prior to expiry). The same applies to the first and subsequent infusions in 
the OLE period of the study (for eligible subjects that choose to participate in the OLE period). 
*
Due to rounding of the total infusion volume by some programmable infusion pumps, an
infusion of 99 mL to 101 mL will be considered a complete infusion and will not be recorded
as a deviation from the study.
Prior to the first dose of study drug (12–24 hours prior to the infusion), subjects will be 
premedicated with oral prednisone (40 mg if body weight is <40 kg, 60 mg if body weight is 
≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg). Subjects will self-administer oral 
prednisone 12–24 hours prior to the start of the first infusion only. As treatment assignment 
during the double-blind, placebo-controlled part of the study will be blinded, all eligible subjects 
that choose to participate in the OLE period of the study will self-administer oral prednisone 
premedication 12–24 hours prior to the first OLE period infusion as well. 
The IV infusion may be interrupted, and/or the rate may be reduced if a subject 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 AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 56 of 140 
Confidential 
completed within 8 hours of preparation. Administration will also be discontinued if a SAE 
occurs during the course of the infusion. If the subject experiences an IRR that causes 
interruption or cessation of the infusion, a blood sample for exploratory safety analysis should be 
collected within 1–2 hours of the onset of symptoms.  
The subject will be observed for at least 1 hour (or greater, as per Investigator discretion) after 
the end of all infusions. In the event of an IRR, the subject may require prolonged observation 
(greater than 1 hour or until the symptoms resolve), as per Investigator discretion. At 1-hour 
postdose, vital signs will be measured and a blood sample will be collected for complete blood 
count (CBC) with differential. Subjects will also be instructed to immediately contact the study 
doctor if any reactions occur after discharge. 
9.7 
Study Drug Storage 
AK002 will be stored by the study sites at 2°C to 8ºC under lock at the designated pharmacy. 
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, this 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 can be used. 
9.8 
Study Drug Accountability 
The site’s study pharmacist/designee is responsible for maintaining accurate and current records 
accounting for receipt, dispensing, preparation, use, return (or destruction), and final disposition 
of all IP. All dosage calculations will be documented on the source documents. The Master IP 
Accountability Log and Endpoint IRT should be used to capture receipt, dispensing, and return 
(or destruction). The study monitor will verify entries on these documents throughout the study.  
10.
Subject Numbering, Stratification, Randomization, and Blinding
10.1 
Subject Numbering 
Each subject who provides informed consent will be assigned a patient identification number 
(PID) that uniquely identifies them as a subject in the study. The PID will consist of a 9-digit 
number: 


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 57 of 140 
Confidential 
•
The first 3 digits designate the study number. For this study, the number is 214.
•
The second 3 digits designate the site number.
•
The last 3 digits designate the order of consent at the site (the first subject who provides
consent is 001, the second subject is 002, and so forth).
The subject will maintain the same PID throughout the entire study. If a subject signs the ICF but 
does not meet the inclusion/exclusion criteria or qualifies for the study but does not enroll, the 
subject may be assigned a new PID and rescreened once. Subjects rescreened within 30 days of 
signing the initial consent will not need to sign a new ICF if no changes have been made to the 
ICF. 
10.2 
Stratification and Randomization 
To be randomized into the study, a subject must meet all inclusion criteria and no exclusion 
criteria. Subjects will be randomized through the IRT system. 
If the subject qualifies for the study after completing all screening procedures, on the day of first 
infusion (Study Day 1), the site will access the IRT system in order to randomize and stratify the 
subject in the study and enter the current body weight for study drug dose calculation. Subjects 
will be stratified at randomization based on age (12–17 and ≥18 years) and baseline DSQ score 
(≤30 and >30). The IRT system will randomly assign the subject to a low dose AK002 regimen 
(6 doses of 1 mg/kg), a high dose AK002 regimen (first dose at 1 mg/kg, subsequent 5 doses at 
3 mg/kg), or placebo in a double-blind approach and will email the kit (vial) number to the study 
pharmacist.  
Approximately 300 subjects with symptomatic EoE will be randomized 1:1:1 to receive 
1 of 3 dose regimens in a double-blind fashion: 100 subjects will be randomized to the low dose 
regimen (1 mg/kg AK002 administered every 4 weeks for 6 doses); 100 subjects will be 
randomized to the high dose regimen (1 mg/kg AK002 for the first dose followed by 3 mg/kg 
AK002 administered every 4 weeks for the 5 subsequent doses); and 100 subjects will be 
randomized to placebo. A subject is considered enrolled in the study when the subject is 
randomized. 
For subsequent infusions on Days 29, 57, 85, 113, and 141, the site will access the IRT system 
on the day of infusion and enter the PID as well as the subject’s body weight, and the system will 
assign the vial(s) on the dose regimen associated with the randomization number. The study 
pharmacist will then receive an email detailing the kit (vial) number to prepare. 


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 5 8  of 1 4 0  
C o nfi de nti al  
Pri or t o eac h i nf usi o n, t h e I n vesti gat or or d esi g nee will c o nfir m t hat t he PI D rec or de d o n t he 
I V ba g pr o vi de d b y t h e st u d y p har macist matc h es t he s u bject. T he s u bject’s i de ntificati o n s h o ul d 
be c o nfir me d a n d d oc u m e nte d b y a sec o n d part y pri or t o a d mi nisteri n g t he i nf usi o n, w he ne ver 
p ossi ble.  
T h e assi g n me nt of treat me nts t o A K 0 0 2 or place b o will be sec urel y retai ne d i n t he I R T s yste m 
u ntil s uc h ti me as desi g nate d b y t he Statistical A nal ysis Pla n.  
1 0. 3  
Bli n di n g  
T he i de ntit y of test a n d c o ntr ol treat me nts will n ot be k n o w n t o I n vesti gat ors, S p o ns or, re searc h 
staff, s u bjects, or t he pri mar y st u d y m o nit or.  
T he f oll o wi n g st u d y pr oce d ures will be i n place t o e ns ure d o u ble- bli n d a d mi nistrati o n of st u d y 
treat me nts: 
•
Access t o t he ra n d o mizati o n c o des will be strictl y c o ntr olle d via t he I R T s yste m.
•
T hr o u g h o ut t he st u d y, t he bli n d s h o ul d re mai n u n br o ke n e xce pt f or a n e mer ge nc y w h e n
k n o wle d ge of a s u bject’s st u d y me dicati o n is necessar y f or f urt her ma n a ge me nt or if
re q uire d f or re g ul at or y re p orti n g. T he Alla k os Me dical M o nit or a p pr o ves a n y e mer ge n c y
bli n d brea k, if at all p ossi ble, pri or t o t he u n bli n di n g.
•
St u d y dr u g vial la bels will be bli n de d, a n d A K 0 0 2 a n d place b o f or i nf usi o n will be i de ntical
i n a p pear a nce.
•
Res ults fr o m a nal ysis of bl o o d sa m ples f or P K a n d A D A will n ot be pr o vi de d t o t he
I n v esti gat or a n d S p o nsor u ntil after fi nal data b ase l oc k.
•
Res ults fr o m a nal ysis of bl o o d sa m ples f or e x pl orat or y a nal ysis or e x pl orat or y safet y
a nal ysis ( u nless i m me diatel y re q uire d f or safet y iss ues) will n ot be pr o vi de d t o t he
I n v esti gat or a n d/ or S p o ns or u ntil after fi nal dat a b ase l oc k of t he d o u bl e- bli n d p orti o n of t he
st u d y.
•
F or ti me p oi nts occ urri n g after t he i nitial i nf usi o n of st u d y dr u g d uri n g t he d o u ble- bli n d
p orti o n of t he st u d y, res ults of t he f oll o wi n g assess me nts will n ot be pr o vi de d t o t he
I n v esti gat or a nd/ or S p o ns or u ntil after fi nal dat a b ase l oc k. T he res ults will be re vie w e d o n
a n o n g oi n g basis b y t he Safet y M o nit or a n d escal ate d as a p pr o priate.
−
Differ e ntial cell c o u nts (i ncl u di n g ne utr o p hils, e osi n o p hils, bas o p hils, m o n oc ytes, a n d
l y m p h oc ytes) fr o m peri p heral bl o o d.
−
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.
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Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 5 9  of 1 4 0  
C o nfi de nti al  
Ot her t ha n f or 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 veal e d after all s u bjects 
ha ve c o m plete d t h eir partici pati o n i n t he d o u ble- bli n d p orti o n of t he st u d y a n d t he data base f or 
t he d o u ble- bli n d p orti o n of t he st u d y has bee n l oc ke d. 
1 0. 4  
E m er ge nc y U n bli n di n g  
Brea ki n g t he bli n d i n a cli nical trial o n a n e mer g e n c y basis b y t he site s h o ul d o nl y occ ur w h e n 
k n o wle d ge of t he tr eat me nt t o w hic h a s u bject was all ocate d w o ul d ha v e i m plicati o ns f or t he 
e mer ge n c y me dical ma n a ge me nt of t he s u bject or if re q uire d f or re g ulat or y re p orti n g. If 
necessar y, e mer ge nc y u n bli n di n g ca n be c o n d uct e d t hr o u g h t he I R T s yste m b y re gistere d site 
users a n d/ or t he M e dical M o nit or. W he ne ver p ossi ble, t he I n vesti gat or s h o ul d c o ntact t he 
Me dical M o nit or bef or e perf or mi n g a n e mer g e nc y brea ki n g of t he bli n d. Reas o n f or u n bli n di n g, 
pers o n c o n d ucti n g t he u n bli n di n g, pers o n(s) w h o k n o w t he u n bli n de d treat me nt, a n d date/ti me of 
u n bli n di n g will be rec or d e d. 
E mer ge nc y u n bli n di n g is n ot a p pr o priate if it bec o mes me dicall y necessar y t o use resc ue t h era p y 
(s wall o we d t o pical c ortic oster oi ds, s yste mic c ortic oster oi ds, or e mer g e nc y es o p ha geal dilati o n). 
S u bject s recei vi n g r esc ue t hera p y s h o ul d re mai n bli n de d, s h o ul d c o nti n ue t o recei v e st u d y dr u g, 
a n d s h o ul d c o nti n ue t o c o m pl y wit h all st u d y visits a n d assess me nts i n acc or da nce wit h t he 
Sc he d ule of E ve nts. A n y s u bject re q uiri n g resc ue t hera p y m ust ha ve a n E G D ( wit h bi o ps y 
c ollecti o n a n d E R E F S sc ori n g) perf or me d pri or t o i nitiati o n of resc ue me di cati o ns or at t he ti me 
of e mer g e nc y dilati o n. T he E G D perf or me d d u e t o t he re q uire m e nt of res c ue t hera p y will be 
use d i nstea d of t he E G D pla n ne d f or D a y 1 6 9 ( Wee k 2 4).  
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 Sc h e d ule of E ve nts de pi cti n g t he re q uire d t esti n g pr oce d ures t o be
perf or me d f or t he d urati o n of t he st u d y.
W he n m ulti ple e val uat i o ns are sc h e d ule d at t he s a me ti me p oi nt, t he pri orit y f or eac h will be as 
f oll o ws:  
•
D uri n g st u d y visits:
−
(self-a d mi nistere d electr o nic f or mat) s h o ul d be c o m plete d at t he b e gi n ni n g of t he
st u d y visit bef ore a n y ot h er assess me nts or pr oce d ures.
−
Vita l si g ns will be o btai ne d after t he s u bject has b ee n at rest f or ≥5 mi n utes.
−
P h ysical e xa mi nati o ns ca n be c o n d ucte d a n d uri ne sa m ples ca n be c ollecte d eit her
bef ore or aft er ot her e val uati o ns, u nless ot her wise s pecifie d.
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Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 6 0  of 1 4 0  
C o nfi de nti al  
•
Dail y (after t he last meal of t he da y):
−
D S Q (e P R O) s h o ul d be c o m plete d dail y after t he l ast meal of t he da y (at a p pr o xi matel y
t he sa me ti me eac h e ve ni n g) d uri n g t he scree ni n g, treat me nt, a n d f oll o w- u p peri o ds.
−
S oli d F o o d Q uesti o n (if a p plica ble) s h o ul d be c o m plete d i m me diatel y after t h e D S Q.
−
O n Da y - 2, D a y 1 5, a n d Da y 2 9, t he 
 s h o ul d be c o m plete d i m me diatel y
after t he D S Q (a n d t he S oli d F o o d Q uesti o n, if a p plica ble) is s u b mitte d.
−
O n Da y 1 5 a n d D a y 2 9, t he 
 s h o ul d be c o m plete d i m me diatel y after t he
D S Q, S oli d F o o d Q uesti o n (if a p plica ble), a n d t h e 
 are s u b mitte d.
−
D uri n g t he scr ee ni n g peri o d o nl y, s u bjects s h o ul d c o m plete t he E G/ E o D P R O
q uesti o n naire dail y aft er c o m pleti o n of t he D S Q, S oli d F o o d Q uesti o n (if a p plica ble),
a n d  
 ( o n Da y - 2).
1 1. 1  
Diet ar y a n d Lifest yle R estricti o ns  
S u bjects s h o ul d mai ntai n t he sa me diet a n d f o o d restricti o ns fr o m t he scree ni n g visit t hr o u g h 
Da y 1 9 7 ( or E T). T he Baseli ne Diet Assess me nt will ca pt ure t he dietar y a n d lifest yle restricti o ns 
a d here d t o pri or t o scree ni n g. C o m plia nce wit h t he baseli ne diet ( pre vi o us dietar y a n d lifest yle 
restricti o ns) will be ca pt ure d i n t he e C R Fs at s u bse q ue nt st u d y visits. 
1 1. 2  
P h ar m ac o d y n a mic/ Effic ac y -R el ate d Pr o ce d ures  
1 1. 2. 1  D ys p h a gi a S y m pt o m Q uesti o n n aire  
T hr o u g h o ut t he d urati o n of st u d y partici pati o n (i n cl u di n g scree ni n g p eri o d, treat me nt peri o d, a n d 
f oll o w- u p peri o d), s u bjects will self -a d mi nister a n electr o nic v ersi o n of t he D S Q ( A p pe n di x 1 ) 
dail y after t he last meal of t he da y at a p pr o xi matel y t he sa me ti me eac h e ve ni n g.   
S u bjects will n ot be a ble t o c o m plete a q uesti o n naire m ore t ha n 2 4 h o urs after it is d ue a n d will 
n ot be a ble t o g o bac k a n d ma ke a n y c orrecti o ns or c ha n ges t o t he d ata ori gi nall y e ntere d. T his 
i nf or mati o n will be a ut o maticall y ca pt ure d a n d m ai ntai ne d i n t he e P R O s yste m of t he E D C.  
A pa per v ersi o n of t he P R O q uesti o n naire is a vail a ble t o s u bjects i n case t h e y are n ot a ble t o 
c o m plete t he electr o nic v ersi o n f or a s h ort peri o d of ti me. O nl y o ne P R O s h o ul d be c o m plete d 
per da y, a n d t h e recall peri o d s h o ul d n ot be m ore t ha n a p pr o xi matel y 2 4 h o urs l o n g. T his 
i nf or mati o n will be ma n uall y ca pt ure d a n d e ntere d i nt o t he E D C b y t he st u d y site.  
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Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 6 1  of 1 4 0  
C o nfi de nti al  
1 1. 2. 2  S oli d F o o d Q uesti o n  
If Q uesti o n 1 o n t he D S Q is a ns wer e d “ N o, ” t he s u bject will recei v e t he S oli d F o o d Q uesti o n 
(A p pe n di x 2 ) after t he y c o m plete a n d s u b mit t he D S Q. T his i nf or mati o n will be a ut o maticall y 
ca pt ure d a n d mai ntai ne d i n t he e P R O s yste m of t he E D C.  
A pa per v ersi o n of t he S oli d F o o d q uesti o n is a vaila ble t o s u bjects i n case t he y are n ot a bl e t o 
c o m plete t he electr o nic v ersi o n f or a s h ort peri o d of ti me. O nl y o ne P R O s h o ul d be c o m plete d 
per da y, a n d t h e recall peri o d s h o ul d n ot be m ore t ha n a p pr o xi matel y 2 4 h o urs l o n g. T his 
i nf or mati o n will be ma n uall y ca pt ure d a n d e ntere d i nt o t he E D C b y t he st u d y site.  
1 1. 2. 3  
 
O n Da y - 2 ( 2 d a ys bef ore Da y 1), o n D a y 1 5 (a p pr o xi matel y 2 wee ks after t he first d ose), a n d o n 
Da y 2 9 (a p pr o xi matel y 4 wee ks after t he first d ose), s u bjects will self- a d mi nister a n electr o ni c 
versi o n of t he 
 (A p p e n di x 3 ) after t he y 
c o m plete a n d s u b mit t he D S Q a n d S oli d F o o d Q u esti o n (if a p plica ble). T his i nf or mati o n will be 
a ut o maticall y ca pt ur e d a n d mai ntai ne d i n t he e P R O s yste m of t he E D C.  
A pa per v ersi o n of t he  
 is a vaila ble t o s u bjects i n case t he y are n ot a bl e t o c o m plete t he 
electr o nic v ersi o n. T his i nf or mati o n will be ma n u all y ca pt ure d a n d e ntere d i nt o t he E D C b y t he 
st u d y site.  
1 1. 2. 4  
 
O n Da y 1 5 ( a p pr o xi matel y 2 wee ks aft er t he first d ose) a n d D a y 2 9 (a p pr o xi matel y 4 wee ks after 
t he first d ose), s u bjects will self-a d mi nister a n electr o nic versi o n of t he 
 
 (A p pe n di x 4 ) after t h e y c o m plete a n d s u b mit t he D S Q, 
S oli d F o o d Q uesti o n (if a p plica ble), a n d  
 T his i nf or mati o n will be a ut o maticall y ca pt ure d 
a n d mai ntai ne d i n t he e P R O s yste m of t he E D C.  
A pa per v ersi o n of t he  
 is a vaila ble t o s u bjects i n case t he y are n ot a ble t o c o m plete t he 
electr o nic v ersi o n f or a s h ort peri o d of ti me. T his i nf or mati o n will be ma n uall y ca pt ure d a n d 
e ntere d i nt o t he E D C b y t he st u d y site. 
1 1. 2. 5  E G/ E o D P R O Q uesti o n n aire  
D uri n g t he scr ee ni n g peri o d o nl y, s u bjects will self -a d mi nister a n electr o ni c versi o n of t he 
E G/ E o D P R O q uesti o n naire ( A p pe n di x 5 ) dail y aft er c o m pleti o n of t he d ail y D S Q, S oli d F o o d 
Q uesti o n (if a p plica ble), a n d  
 ( o n Da y - 2).  
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Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 6 2  of 1 4 0  
C o nfi de nti al  
S u bject s will n ot be a ble t o c o m plete a q uesti o n naire m ore t ha n 2 4 h o urs after it is d ue a n d will 
n ot be a ble t o g o bac k a n d ma ke a n y c orrecti o ns or c ha n ges t o t he d ata ori gi nall y e ntere d. T his 
i nf or mati o n will be a ut o maticall y ca pt ure d a n d m ai ntai ne d i n t he e P R O s yste m of t he E D C.  
A pa per v ersi o n of t he P R O q uesti o n naire is a vail a ble t o s u bjects i n case t h e y are n ot a ble t o 
c o m plete t he electr o nic v ersi o n f or a s h ort peri o d of ti me. O nl y o ne P R O s h o ul d be c o m plete d 
per da y, a n d t h e recall peri o d s h o ul d n ot be m ore t ha n a p pr o xi matel y 2 4 h o urs l o n g. T his 
i nf or mati o n will be ma n uall y ca pt ure d a n d e ntere d i nt o t he E D C b y t he st u d y site.  
1 1. 2. 6  
 
A n electr o nic v ersi o n of t he  
( A p p e n di x 6 ) will be self -a d mi nistere d b y t he s u bject via 
t heir pers o nal el ectr o nic de vice d uri n g scree ni n g, pre d ose 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), o n Da y 1 6 9, a n d o n Da y 1 9 7 ( or E T). T his i nf or mati o n will be a ut o maticall y 
ca pt ure d a n d mai ntai ne d i n t he e P R O s yste m of t he E D C.  
A pa per v ersi o n of t he 
 is a vaila bl e t o s u bjects i n case t he y are n ot a ble t o c o m plete t he 
electr o nic v ersi o n at a n y gi ve n ti me p oi nt. T his i nf or mati o n will be ma n uall y ca pt ure d a n d 
e ntere d i nt o t he E D C b y t he st u d y site.  
1 1. 2. 7  Es o p h a g o- G astr o -D u o de n osc o p y 
A n E G D will be perf or m e d d uri n g t he scree ni n g p eri o d a n d a g ai n o n Da y 1 6 9 ( ± 3 da ys). D uri n g 
t he E G D, e n d osc o pi c se v erit y will be gra de d p er t he E o E Refere nce Sc ore f or E n d osc o pic 
A b n or malities a n d bi o psies will be c ollecte d. Res ults fr o m t he Da y  1 6 9 E G D bi o psies will n ot be 
pr o vi de d t o t he I n vesti gat or a n d/ or S p o ns or u ntil after fi nal dat a base l oc k a n d u n bli n di n g. T he 
Safet y M o nit or will re vie w t he E G D r es ults a n d es calate a n y iss ues t o t he Me dical M o nit or a n d 
t he I n v esti gat or, as a p pr o priate, w hile mai ntai ni n g t he bli n d. 
1 1. 2. 7. 1  E osi n o p hilic Es o p h a gitis Refere nce Sc o re f o r E n d osc o pic  A b n or m alities  
D uri n g t he c o n d uct of t h e E G D at scree ni n g a n d o n Da y 1 6 9 ( or E T), t he atte n di n g p h ysicia n 
will assess a n d gra d e e de ma, ri n gs, e x u dates, f urr o ws, a n d strict ure s p er t he E R E F S. T he E R E F S 
a n d t he E R E F S Sc ori n g T o ol s o urce ca n be f o u n d i n t he st u d y hist ol o g y ma n ual. 
1 1. 2. 7. 2  E G D Bi o ps y C ollecti o n  
D uri n g t he c o n d uct of t h e E G D at scree ni n g a n d o n Da y 1 6 9 ( or E T), a bi o ps y sa m ple will be 
c ollecte d acc or di n g t o sta n dar dize d i nstr ucti o ns i n t he st u d y hist ol o g y ma n ual a n d will be se nt t o 
t he ce ntral hist ol o g y la b f or fi xi n g a n d stai ni n g.  
A bli n de d ce ntral rea d er will assess a n d re p ort t he ma xi m u m n u m ber of e osi n o p hils/ h pf, 
 
C CI
C CI
C CI
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 6 3  of 1 4 0  
C o nfi de nti al  
 
 
 
 (A p pe n di x 9 ).  
T he Scree ni n g E G D bi o ps y tiss ue res ults m ust be a vaila ble t o verif y eli gi bilit y per t he f oll o wi n g. 
•
I n cl usi o n Criteri o n # 2: C o nfir me d dia g n osis of E o E a n d i ntrae pit helial e osi n o p hilic
i nfiltrati o n of ≥1 5 e osi n o p hils/ h pf i n 1 h pf fr o m t he bi o ps y 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 ca use f or t he es o p ha g eal e osi n o p hilia.
•
E xcl usi o n Criteri o n # 1: C o nc o mita nt m o deratel y or se verel y s y m pt o matic E G a n d/ or E o D * ,
defi ne d as:
−
≥3 0 e osi n o p hils/ h pf i n 5 h pf i n t he st o mac h ( E G) 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 o D) wit h o ut a n y ot her ca us e f or e osi n o p hilia 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.
a n d 
−
E G/ E o D P R O Q uesti o n naire wee kl y a vera g e si n gle s y m pt o m sc ore of ≥3 d uri n g t he last
2 wee ks of s cree ni n g f or 1 of t he f oll o wi n g s y m pt o ms: a b d o mi nal pai n, na usea, a n d/ or
diarr hea.
*
T his e xcl usi o n criteri o n is o nl y a p plica ble t o sites acti vel y e nr olli n g s u bj ect s i n t he
A K 0 0 2 - 0 1 6 st u d y. If a site is n ot  acti vel y scree ni n g a n d e nr olli n g s u bjects i n t he
A K 0 0 2 - 0 1 6 st u d y, t he n t his e xcl usi o n criteri o n is n ot a p plica ble.
•
E xcl usi o n Criteri o n # 7: Acti ve Helic o b a cter pyl ori * *  i nfecti o n as deter mi ne d b y ce ntral
hist ol o g y stai ni n g of t he bi o ps y c ollecte d d uri n g t he Scree ni n g E G D.
* * If a n acti ve H.  pyl ori i nfecti o n at scree ni n g is treat e d wit h sta n dar d of care t hera pies, t he
s u bject’s s y m pt o ms re mai n sta ble, a n d t he s u bject is t he n c o nfir me d ne g ati ve f or 
H. pyl ori , t he s u bject ma y be ra n d o mize d i nt o t he st u d y.
1 1. 2. 8  C o m plete Bl o o d C o u nt wit h Differe nti al  
Bl o o d f or C B C wit h differe ntial will be o btai ne d at all st u d y visits. 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 C B C wit h differe ntial will be dra w n t wice: pre d ose a n d 1 h o ur 
p ost d ose.  
T he bl o o d sa m ple will be pr ocesse d a n d s hi p pe d i n acc or d a nce wit h t he ce ntral la b orat or y 
ma n ual a n d la b kit i nstr ucti o ns. T he ce ntral la b orat or y will a nal yze t he bl o o d sa m ple a n d pr o vi de 
res ults f or C B C wit h differe ntial, i ncl udi n g he m o gl o bi n, he mat ocrit, platelet c o u nt, re d bl o o d cell 
c o u nt, w hite bl o o d cell c o u nt, a n d a bs ol ute differe ntial c o u nt ( ne utr o p hils, l y m p h oc ytes, 
m o n oc ytes, e osi n o p hils, a n d bas o p hils). 
C CI
C CI


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As described in the Investigator’s Brochure, expected effects of AK002 include changes in 
absolute lymphocyte and eosinophil counts, so these results could potentially unblind the blinded 
members of the study. Consequently, with the exception of screening and Day 1 predose, the 
CBC differential results (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) will 
be blinded to both the Sponsor and the study site. The CBC differential results for Day 1 (1 hour 
postdose), Days 8, 15, 29, 57, 85, 113, 141, 169, and 197 (or ET) will therefore be unavailable 
during the study and will not be provided to the Sponsor or study site until after final database 
lock and unblinding.  
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.  
If the CBC differential results from Day 197 (or ET) show that absolute lymphocyte and/or 
eosinophil counts have not recovered (to normal range or baseline levels), the subject must return 
for Extended Follow-Up visits approximately every 28 days to monitor blood counts until 
lymphocyte and/or eosinophil counts have recovered. Extended Follow-Up visits will consist 
only of blood collection for CBC with differential and collection of any AESI and SAE. 
11.2.9 
Baseline Diet Assessment 
During the screening visit, the Investigator or designee will interview the subject and perform a 
Baseline Diet Assessment using the series of standardized dietary assessment questions found in 
Appendix 7. The Baseline Diet Assessment includes questions regarding eating patterns, food 
avoidance behaviors, and allergies, and will serve to establish the “Baseline Diet.” Answers will 
be documented in the subject source documents and recorded in the eCRF.  
If the subject is on diet therapy, the diet therapy and length of time on the current diet therapy 
will be documented during the Baseline Diet Assessment. Per Exclusion Criterion #11, the 
subject is ineligible if any changes were made to the diet therapy during the 8 weeks prior to 
screening. Additionally, if the Baseline Diet Assessment reveals preexisting dietary restrictions, 
the subject must be willing to maintain the same dietary restrictions (“Baseline Diet”) for the 
entire duration of study participation per Inclusion Criterion #7. 
11.2.10 Baseline Diet Compliance 
Per Inclusion Criteria #7, the Baseline Diet (as defined and documented during the Baseline Diet 
Assessment) should be adhered to and maintained as much as possible for the entire duration of 
study participation, even if the subject feels the dietary restrictions are no longer necessary.  


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Confidential 
Compliance with the Baseline Diet will be discussed and assessed during study visits on Days 1, 
15, 29, 57, 85, 113, 141, 169, and 197 (or ET). The Investigator or designee will document 
whether the subject was compliant with the Baseline Diet and, if not, all variances or deviations 
from the Baseline Diet will be documented in the source documents and eCRF.  
11.3 
Safety-Related Procedures 
11.3.1 
Concomitant Medications 
All prior and concomitant medication and concurrent therapies will be documented at screening 
and assessed at all study visits. Concomitant medications, dose, route, unit, frequency of 
administration, indication for administration, dates of medication, and all changes will be 
captured. All prior medications (within 30 days before screening) and concomitant medications 
(during study participation from screening through Day 197 or ET) will be recorded.  
For subjects participating in the OLE period, concomitant medications should be recorded in the 
AK002-014 treatment period database up until the first open-label dose is administered during 
the Day 176 visit. This includes the prednisone premedication administered prior to the Day 176 
visit in the OLE period, which should be recorded in the Concomitant Medications CRF of both 
the AK002-014 treatment period database and the AK002-014 OLE period database. Rescue 
medications and procedures must be documented as rescue treatment in the source documents 
and on the prior and concomitant medications eCRF. 
11.3.2 
Stool Sample for Ova and Parasite 
During the screening visit, subjects will be provided fecal collection kits for the Ova and Parasite 
(O&P) test. Subjects will take the kit home to collect a stool sample. Subjects must return the 
stool sample to the site on the day of collection (or within 24 hours of collection). The site will 
process and ship the stool sample per the central laboratory manual. The central laboratory will 
test the stool sample for O&P. Per Exclusion Criterion #8, a positive O&P result would make the 
subject ineligible, and a negative O&P result is required to confirm eligibility. Alternatively, a 
negative result from a helminth test done within 90 days prior to screening may be used to 
confirm eligibility, at the discretion of the Investigator.  
11.3.3 
Body Weight and Height 
Height (in centimeters) and body weight (in kilograms) will be measured at screening and body 
mass index (BMI) will be calculated. Body weight must be measured prior to each dose of study 
drug (predose on Days 1, 29, 57, 85, 113, and 141). Predose weight should be measured at the 
site on the day before the study drug infusion or on the day of the study drug infusion, entered 
into the IRT system, and recorded on the IP Dose Calculation and Preparation Worksheet 
maintained by the study pharmacist for each subject’s dose calculations.  


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Confidential 
Body weight will also be measured at the end of the treatment period (on Day 169) and at the 
end of study (Day 197 or ET).  
11.3.4 
Vital Signs 
Vital signs including systolic and diastolic blood pressure, pulse, body temperature, and 
respiratory rate will be taken after the subject has been at rest for ≥5 minutes and, if possible, 
before any blood draw.  
Vital signs will be measured during screening and on Days 1, 15, 29, 57, 85, 113, 141, 169, and 
197 (or ET). On dosing days (Days 1, 29, 57, 85, 113, and 141), vital signs will be measured 
predose, 15 minutes (±5 minutes) after the infusion start time, immediately postdose (within 
5 minutes after the infusion end time), and 1 hour (±5 minutes) postdose. Please refer to the 
schedule in Table 1. 
11.3.5 
Complete Physical Examination 
A complete physical exam will be performed during the screening visit by the Investigator or 
qualified Subinvestigator. A complete physical exam will include the following body system or 
organ assessments: skin; head, eyes, ears, nose, and throat; thyroid; lungs; cardiovascular; 
abdomen; extremities; lymph nodes; and a brief neurological examination.  
The Investigator or qualified Subinvestigator will examine abnormalities and assess whether they 
are clinically significant or not clinically significant. All clinically significant abnormalities 
noted during the complete physical exam should be captured as a baseline condition in the 
Medical History source document and eCRF.  
11.3.6 
Symptom-Directed Physical Examination 
If a new or worsening symptom (or clinically significant finding) is observed or reported, the 
Investigator (or qualified Subinvestigator) will perform a symptom-directed physical exam. The 
symptom-directed physical exam will focus only on body systems and/or organs with symptoms 
or warranting examination in the opinion of the Investigator or Subinvestigator. A symptom-
directed physical exam will be performed only as needed, but may occur at any visit, predose, 
during infusions, and/or postdose (including for IRR). Clinically significant findings will be 
captured as an AE, followed by the Investigator, and managed appropriately per standard of care. 
11.3.7 
Electrocardiogram 
A 10-lead or 12-lead ECG (without intensive QT analysis) will be obtained during screening 
after the subject has been in the supine position for ≥5 minutes and, if done on the same day as 
blood collection, before blood is drawn. The Investigator or qualified Subinvestigator will review 


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the ECG and assess any abnormalities for clinical significance. Any clinically significant 
findings will be captured as a baseline condition in the Medical History source document and 
eCRF. The ECG will be used to identify diseases or conditions that would put the subject at 
increased risk if participating in a clinical trial, so this should be considered when evaluating 
eligibility. 
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 treatment planning 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 (Sections 11.4.1–11.4.10). For any laboratory test value outside the 
reference range that the Investigator considers clinically significant, the Investigator will: 
•
Repeat the test to verify the out-of-range value.
•
Follow the out-of-range value to a satisfactory clinical resolution.
•
Record as an AE, any laboratory test value after start of study drug that:
−
The Investigator considers clinically significant
−
Requires a subject to be discontinued from the study, or
−
Requires a subject to receive treatment.
Clinical laboratory testing will be performed centrally but may be performed locally due to 
issues associated with the coronavirus pandemic. 
Testing for COVID-19 is not required for this study but may be implemented by the study site at 
any time during the clinical study due to safety regulations or procedures. 
11.4.1 
Complete Blood Count with Differential 
Blood will be obtained for CBC with differential as described in Section 11.2.8. 
11.4.2 
Blood Chemistry Profile 
Blood will be obtained for chemistry tests during screening, predose on dosing days (Days 1, 29, 
57, 85, 113, and 141), and on Days 169 and 197 (or ET). The blood sample will be processed and 
serum aliquots shipped per the central laboratory manual and laboratory kit instructions. The 
central laboratory will analyze the serum sample and provide results for chemistry tests including 
sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, creatinine, creatine 


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Amendment 6 
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Confidential 
kinase, calcium, phosphorus, magnesium, total and direct bilirubin, total protein, albumin, 
alkaline phosphatase, alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, 
and lactate dehydrogenase.  
11.4.3 
Urinalysis 
Urine will be obtained for urinalysis during screening, as needed (if warranted in the opinion of 
the Investigator or Subinvestigator), and on Day 197 (or ET). The urine sample will be processed 
and shipped in accordance with the central laboratory manual and laboratory kit instructions. The 
central laboratory will analyze the urine sample for specific gravity, pH, protein, glucose, 
ketones, blood, and leukocyte esterase.  
11.4.4 
Serum Pregnancy and Follicle-Stimulating Hormone 
Blood will be obtained from all female subjects of childbearing potential for a serum pregnancy 
test as measured by human chorionic gonadotropin (hCG). Females who are surgically sterile 
(tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 3 months and females who 
are postmenopausal for at least 1 year with FSH level >30 mIU/mL are not considered to be of 
childbearing potential. To determine whether female subjects are post-menopausal or are of 
childbearing potential, blood for serum FSH will be obtained from all females during screening. 
The blood sample will be processed and shipped per the central laboratory manual and laboratory 
kit instructions. Both serum hCG and serum FSH will be analyzed by the central laboratory. 
Females of childbearing potential (females with screening FSH level ≤30 mIU/mL) will provide 
a urine sample predose on dosing days (Days 1, 29, 57, 85, 113, and 141) for pregnancy (hCG) 
testing. The site will perform the urine pregnancy (hCG) test using an indicator stick from the kit 
supplied by the central laboratory. This test is to be assessed by the study staff, and study staff 
should confirm the subject is not pregnant prior to the start of each study drug infusion.  
11.4.5 
Serology 
Blood will be obtained during screening for serology tests including hepatitis B surface antigen 
(HbsAG), hepatitis C antibody, hepatitis B core antibody (anti-HBc), human immunodeficiency 
virus (HIV), and Strongyloides stercoralis. The blood sample will be processed and shipped to 
the central laboratory in accordance with the central laboratory manual and lab kit instructions.  
Per Exclusion Criterion #8, subjects are not eligible if they are seropositive for Strongyloides 
stercoralis. Per Exclusion Criterion #9, subjects are not eligible if they are seropositive for HIV. 
Exclusion Criterion #9 also excludes subjects seropositive for hepatitis (HbsAG, hepatitis C 
antibody, or anti-HBc), except for vaccinated subjects or subjects with a history of hepatitis that 
has since resolved.  


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11.4.6 
Total Serum IgE 
Blood will be collected for total serum IgE on Day 1 (predose), Day 85 (predose), and Day 169 
(or ET, if subject early terminates before Day 169). The blood sample will be processed and 
serum aliquots will be shipped frozen in accordance with the central laboratory manual and 
laboratory kit instructions. The central laboratory will analyze the serum samples for total 
serum IgE. 
11.4.7 
Anti-Drug (AK002) Antibodies 
Blood for assessment of ADA will be collected predose on dosing days (Days 1, 29, 57, 85, 113, 
and 141) and at the end of study on Day 197 (or ET). In addition, an unscheduled blood sample 
for ADA may be obtained if an AE is suspected to be related to immunogenicity. The blood 
sample will be processed and serum aliquots shipped frozen in accordance with the central 
laboratory manual and lab kit instructions. The central laboratory will analyze the sample for 
ADA using a validated assay method. 
11.4.8 
Pharmacokinetics 
Blood for assessment of AK002 concentrations (PK) will be collected on Days 1, 8, 15, 29, 57, 
85, 113, 141, 169, and 197 (or ET). On dosing days (Days 1, 29, 57, 85, 113, and 141), blood for 
PK will be obtained predose. The blood samples will be processed and serum aliquots shipped 
frozen in accordance with the central laboratory manual and laboratory kit instructions.  
AK002 concentrations will be assessed by the central laboratory (or designee) using a validated 
ELISA method. Refer to the central laboratory manual for additional information on PK sample 
collection, processing, storage, shipment, and analysis.  
11.4.9 
Blood for Exploratory Analysis 
Blood samples for exploratory analyses will be collected during screening and on Days 15, 169, 
and 197 (or ET). The blood sample will be processed and serum aliquots shipped frozen in 
accordance with the central laboratory manual and laboratory kit instructions. Serum samples 
will be analyzed for exploratory biomarkers by the central laboratory or designee. 
11.4.10 Blood for Exploratory Safety Analysis 
There are no planned blood collections for exploratory safety. Blood will only be collected for 
exploratory safety if the infusion is interrupted or permanently discontinued due to an IRR. If an 
IRR results in infusion interruption or cessation, blood for exploratory safety should be obtained 
within 1–2 hours of IRR symptom onset. The blood sample will be processed and serum aliquots 
shipped frozen in accordance with the central laboratory manual and laboratory kit instructions. 
Exploratory safety analytes will be measured by the central laboratory or designee. 


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 7 0  of 1 4 0  
C o nfi de nti al  
1 2.
E v al u ati o ns a n d Pr oce d ures b y Visit
E val uati o ns a n d pr oce d ur es b y visit are s h o w n i n Ta ble  1.
Ge ner al I nf or m ati o n:  
•
All rec or d e d cl oc k ti mes s h o ul d utilize a 2 4 - h o ur cl oc k.
•
Da y 1 is t he da y o f t he first d ose.
•
Scree ni n g pr o ce d ur es ma y be perf or me d o ver m ulti ple da ys pri or t o t he first d ose.
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)
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.
3)
C ollect de m o gra p hics a n d me dical  hist or y.
4)  
A d d t he s u bject i n E D C t o assi g n a PI D.
5)
C o m plete i n Scree ni n g Visit Date e C R F b y selecti n g “I nitiate Visit.”
6)
Acti vate electr o nic q uesti o n naires (e P R Os) a n d pr o vi de s u bject wit h Vie d o c Me user n a me
a n d PI N.
7) 
Trai n s u bject o n dail y c o m pleti o n of t he D S Q, S oli d F o o d Q uesti o n (if a p plica ble), a n d t h e
E G/ E o D P R O Q uesti o n naire.
8)
Ha ve t he s u bject c o m plet e t he 
 q u esti o n naire via Vie d oc M e usi n g t heir pers o nal
electr o nic d e vice w hile t he y are at t he site. Re mi n d t he s u bject t o be gi n c o m pl eti n g t he
dail y q uesti o n naires aft er t he last meal of t he da y.
9)
Pr o vi de s u bject a st o ol c ollecti o n kit a n d i nstr uct t he m t o ret ur n t he st o ol sa m ple t o t he site
wit hi n 2 4 h o urs of c ollecti o n ( u nless s u bject ca n pr o vi de sa m ple w hile o n site).
1 0)
Perf or m B aseli ne Diet Assess me nt.
1 1) Rec or d pri or a n d c o nc o mita nt me dicati o ns.
1 2)  Deter mi ne b o d y w ei g ht a n d hei g ht.
1 3)  O btai n vital si g ns bef ore bl o o d dra ws.
1 4)
Perf or m a c o m plet e p h ysical e xa mi nati o n.
1 5)  O btai n a 1 0- lea d or 1 2-lea d E C G bef ore bl o o d dra w.
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 7 1  of 1 4 0  
C o nfi de nti al  
1 6) C ollect t he f oll o wi n g sa m ples f or t he ce ntral la b orat or y:
a) Ser u m pre g na n c y test a n d F S H (f or fe male s u bj ects)
b) Ser ol o g y
c)
C B C wit h differe ntial
d)
C he mistr y
e)
Uri nal ysis
f)
Bl o o d f or e x pl orat or y a n al ysis
1 7)
Perf or m a Scr ee ni n g/ Bas eli ne E G D wit h e n d osc o pic se verit y gra di n g p er E R E F S a n d
bi o ps y c ollecti o n per t he st u d y hist ol o g y ma n ual.
1 8)
O btai n Hist ol o g y Res ults Re p ort fr o m t he Ce ntral Hist ol o g y Rea der, c o nfir m i ntrae pit helial
e osi n o p hilic i nfiltrati o n is e n o u g h t o q ualif y t he s u bject f or t he st u d y a n d t hat t here are n o
e xcl usi o nar y criteria f o u n d o n t he E G D.
1 9) E val uate eli gi bilit y o n a n o n g oi n g basis as t he scree ni n g assess me nt res ults are o btai ne d.
1 2. 2  
T he D a y Bef ore t he First I nf usi o n  
1)
C o nfir m eli gi bilit y.
2) 
S u bje ct will self-a d mi nister oral pre d nis o ne pre m e dicati o n ( d ose b ase d o n b o d y wei g ht)
1 2 – 2 4 h o urs pri or t o t he pla n ne d i nf usi o n start ti me. E ns ure t his is d oc u me nte d
c o nte m p ora ne o usl y ( e. g., s u bject e mails t he site w he n ta ki n g t he pre me di cati o n, s u bject
te xts t he St u d y C o or di nat or w he n ta ki n g t he pre me dicati o n, etc.).
1 2. 3  
D a y 1 – D ose 1  
1)
Pre -I nf usi o n:
a)
C o nfir m c o nti n ue d eli gi bilit y.
b) 
t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
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 i ncl u di n g c o nfir mi n g a n d
d oc u me nti n g t he date a n d ti me t he s u bject self- a d mi nistere d pre me dicati o n.
e)
D oc u me nt a n y c h a n ges t o baseli ne diet.
f)
Deter mi ne b o d y w ei g ht.
g)
C ollect vital si g ns.
C CI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 72 of 140 
Confidential 
h) Perform symptom-directed physical exam, as needed.
i)
Collect the following samples for the central laboratory:

Total Serum IgE

CBC with differential

Chemistry

Pharmacokinetics

Anti-drug antibodies

Urinalysis, if warranted in the opinion of the Investigator or Subinvestigator
j)
Perform urine pregnancy test (if subject is of childbearing potential).
k) Enter the subject’s PID and body weight in the IRT system to randomize the subject.
l)
Once the subject has been randomized in the IRT system, the pharmacist will receive an
email with PID, body weight, and kit number.
m) The study pharmacist will prepare study drug using the weight obtained at the visit. The
final combined volume of the IV bag of study drug + 0.9% NaCl will be 120 mL.
Note: 100 mL of the calculated dose of study drug will be administered to the subject.
The extra 20 mL is to be used to prime the IV infusion line during the preparation of the
IV line at the bedside or to be left over in the infusion bag.
2)
During the Infusion of Study Drug:
a) Infuse 100 mL of study drug over at least 4 hours using an infusion pump per the
instructions and infusion rate schedule in the Administration of Investigational Product
section of the Pharmacy Manual. 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 infusion.
c) Perform symptom-directed physical exam, as needed.
d) If the subject experiences an IRR that causes an interruption or cessation of the study
drug infusion, a blood sample should be collected within 1–2 hours of the onset of
symptoms for exploratory safety analysis. An unscheduled ADA blood sample may be
obtained if an immunogenicity-related AE is suspected.


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 73 of 140 
Confidential 
3)
Post-Infusion:
a) Subject will remain at the study site for at least 1 hour postdose for observation. In the
event of an IRR, the subject may require prolonged observation (>1 hour or until the
symptoms resolve), as per Investigator discretion.
b) Perform symptom-directed physical exam, as needed.
c) Collect vital signs immediately (+5 minutes) following the end of infusion and 1 hour
(±5 minutes) postdose.
d) Collect CBC with differential 1 hour (±15 minutes) after the end of the infusion.
e) Subject will be instructed to immediately contact the study doctor if any reactions occur
after discharge.
12.4 
Day 8 (±1) 
1)
Document any changes to health status.
2)
Document any changes to concomitant medications.
3)
Collect the following samples for the central laboratory:
a) CBC with differential
b) Pharmacokinetics
12.5 
Day 15 (±2) 
1)
Document any changes to health status.
2)
Document any changes to concomitant medications.
3)
Document any changes to baseline diet.
4)
Collect vital signs.
5)
Perform symptom-directed physical exam, as needed.
6)
Collect the following samples for the central laboratory:
a) CBC with differential
b) Pharmacokinetics
c) Blood for exploratory analysis
d) Urinalysis, if warranted in the opinion of the Investigator or Subinvestigator


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 7 4  of 1 4 0  
C o nfi de nti al  
1 2. 6  
D a y 2 9 ( ± 3) – D ose 2  
1)
Pre -I nf usi o n:
a)
C o nfir m c o nti n ue d eli gi bilit y.
b) 
 t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
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)
Deter mi ne b o d y w ei g ht.
g)
C ollect vital si g ns.
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
i) 
C ollect t he f oll o wi n g sa m ples f or t he ce ntral la b orat or y:

C B C wit h differe ntial

C he mistr y

P har mac o ki netics

A nti- dr u g a nti b o dies

Uri nal ysis, if warr a nte d i n t he o pi ni o n of t he I n vesti gat or or S u bi n vesti gat or
j)
Perf or m uri ne pre g na n c y test (if s u bject is of c hil d beari n g p ote ntial).
k)
E nter t he s u bject’s PI D a n d b o d y wei g ht i n t he I R T s yste m f or I P kit assi g n me nt.
l)
T he p har macist will recei ve a n e mail wit h PI D, b o d y wei g ht, a n d kit n u m ber.
m)
T he st u d y p har 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 he calc ulate d d ose of st u d y dr u g will be a d mi nistere d t o t he s u bject. T he 
e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he pre parati o n of t he I V 
li ne at t he be dsi de or t o b e left o ver i n t he i nf usi o n ba g. 
2)  
D uri n g t he I nf usi o n of St u d y Dr u g:
a)
I nf use 1 0 0 m L of st u d y dr u g o ver at least 3 h o urs usi n g a n i nf usi o n p u m p per t he
i nstr ucti o ns a n d i nf usi o n rate sc h e d ule i n t he A d mi nistrati o n of I n v esti gati o nal Pr o duct
secti o n of t he P har mac y Ma n ual. 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 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 7 5  of 1 4 0  
C o nfi de nti al  
c)
Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
d) If t he s u bject e x p erie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y
dr u g i nf usi o n, a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of
s y m pt o ms f or e x pl orat or y safet y a n al ysis. A n u nsc he d ule d A D A bl o o d sa m ple ma y be
o btai ne d if a n i m m u n o ge nicit y- relate d A E  is s us p ecte d.
3) 
P ost-I nf usi o n:
a)
S u bject will re mai n at t he st u d y site f or at least 1 h o ur p ost d ose f or o bser v ati o n. I n t he
e ve nt of a n I R R, t he s u bj ect ma y re q uire pr ol o n ge d o bser vati o n ( > 1 h o ur or u ntil t he
s y m pt o ms res ol ve), as per I n vesti gat or discreti o n.
b) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
c)
C ollect vital si g ns i m me diatel y ( + 5 mi n utes) f oll o wi n g t he e n d of i nf usi o n a n d 1 h o ur
( ± 5 mi n utes) p ost d ose.
d) 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.
e)
S u bject will be i nstr ucte d t o i m me diatel y c o ntact t he st u d y d oct or if a n y reacti o ns occ ur
after disc h ar ge.
1 2. 7  
D a y 5 7 ( ± 3) – D ose 3  
1)
Pre -I nf usi o n:
a)
C o nfir m c o nti n ue d eli gi bilit y.
b) 
 t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
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)
Deter mi ne b o d y w ei g ht.
g)
C ollect vital si g ns.
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
i)
C ollect t he f oll o wi n g sa m ples f or t he ce ntral la b orat or y:

C B C wit h differe ntial

C he mistr y

P har mac o ki netics

A nti- dr u g a nti b o dies

Uri nal ysis, if warr a nte d i n t he o pi ni o n of t he I n vesti gat or or S u bi n ve sti gat or
C CI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 76 of 140 
Confidential 
j)
Perform urine pregnancy test (if subject is of childbearing potential).
k) Enter the subject’s PID and body weight in the IRT system for IP kit assignment.
l)
The pharmacist will receive an email with PID, body weight, and kit number.
m) The study pharmacist will prepare study drug using the weight obtained at the visit. The
final combined volume of the IV bag of study drug + 0.9% NaCl will be 120 mL.
Note: 100 mL of the calculated dose of study drug will be administered to the subject.
The extra 20 mL is to be used to prime the IV infusion line during the preparation of the
IV line at the bedside or to be left over in the infusion bag.
2)
During the Infusion of Study Drug:
a) Infuse 100 mL of study drug over at least 2 hours using an infusion pump per the
instructions and infusion rate schedule in the Administration of Investigational Product
section of the Pharmacy Manual. 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 infusion.
c) Perform symptom-directed physical exam, as needed.
d) If the subject experiences an IRR that causes an interruption or cessation of the study
drug infusion, a blood sample should be collected within 1–2 hours of the onset of
symptoms for exploratory safety analysis. An unscheduled ADA blood sample may be
obtained if an immunogenicity-related AE is suspected.
3)
Post-Infusion:
a) Subject will remain at the study site for at least 1 hour postdose for observation. In the
event of an IRR, the subject may require prolonged observation (>1 hour or until the
symptoms resolve), as per Investigator discretion.
b) Perform symptom-directed physical exam, as needed.
c) Collect vital signs immediately (+5 minutes) following the end of infusion and 1 hour
(±5 minutes) postdose.
d) Collect CBC with differential 1 hour (±15 minutes) after the end of the infusion.
e) Subject will be instructed to immediately contact the study doctor if any reactions occur
after discharge.


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 7 7  of 1 4 0  
C o nfi de nti al  
1 2. 8  
D a y 8 5 ( ± 3) – D ose 4  
1)
Pre -I nf usi o n:
a)
C o nfir m c o nti n ue d eli gi bilit y.
b) 
 t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
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)
Deter mi ne b o d y w ei g ht.
g)
C ollect vital si g ns.
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
i)
C ollect t he f oll o wi n g sa m ples f or t he ce ntral la b orat or y:

C B C wit h differe ntial

C he mistr y

P har mac o ki netics

A nti- dr u g a nti b o dies

T otal Ser u m I g E

Uri nal ysis, if warr a nte d i n t he o pi ni o n of t he I n vesti gat or or S u bi n vesti gat or
j)
Perf or m uri ne pre g na n c y test (if s u bject is of c hil d beari n g p ote ntial).
k) E nter t he s u bject’s PI D a n d b o d y wei g ht i n t he I R T s yste m f or I P kit assi g n me nt.
l)
T he p har macist will recei ve a n e mail wit h PI D, b o d y wei g ht, a n d kit n u m ber.
m)
T he st u d y p har 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 he calc ulate d d ose of st u d y dr u g will be a d mi nistere d t o t he s u bject.
T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g pre parati o n of t he I V
li ne at t he be dsi de or t o b e left o ver i n t he i nf usi o n ba g.
2)  
D uri n g t he I nf usi o n of St u d y Dr u g:
a)
I nf use 1 0 0 m L of st u d y dr u g o ver at least 2 h o urs usi n g a n i nf usi o n p u m p per t he
i nstr ucti o ns a n d i nf usi o n rate sc h e d ule i n t he A d mi nistrati o n of I n v esti gati o nal Pr o d uct
secti o n of t he P har mac y Ma n ual. 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 v ital 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 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 7 8  of 1 4 0  
C o nfi de nti al  
c)
Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
d) If t he s u bject e x p erie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y
dr u g i nf usi o n, a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of
s y m pt o ms f or e x pl orat or y safet y a n al ysis. A n u nsc he d ule d A D A bl o o d sa m ple ma y be
o btai ne d if a n i m m u n o ge nicit y- relate d A E  is s us p ecte d.
3) 
P ost-I nf usi o n:
a)
S u bject will re mai n at t he st u d y site f or at least 1 h o ur p ost d ose f or o bser v ati o n. I n t he
e ve nt of a n I R R, t he s u bj ect ma y re q uire pr ol o n ge d o bser vati o n ( > 1 h o ur or u ntil t he
s y m pt o ms res ol ve), as per I n vesti gat or discreti o n.
b) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
c)
C ollect vital si g ns i m me diatel y ( + 5 mi n ute s) f oll o wi n g t he e n d of i nf usi o n a n d 1 h o ur
( ± 5 mi n utes) p ost d ose.
d) 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.
e)
S u bject will be i nstr ucte d t o i m me diatel y c o ntact t he st u d y d oct or if a n y reacti o ns occ ur
after disc h ar ge.
1 2. 9  
D a y 1 1 3 ( ± 3) – D ose 5  
1)
Pre -I nf usi o n:
a)
C o nfir m c o nti n ue d eli gi bilit y.
b) 
t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
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)
Deter mi ne b o d y w ei g ht.
g)
C ollect vital si g ns.
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
i)
C ollect t he f oll o wi n g sa m ples f or t he ce ntral la b orat or y:

C B C wit h differe ntial

C he mistr y

P har mac o ki netics

A nti- dr u g a nti b o dies

Uri nal ysis, if warr a nte d i n t he o pi ni o n of t he I n vesti gat or or S u bi n vesti gat or
C CI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 79 of 140 
Confidential 
j)
Perform urine pregnancy test (if subject is of childbearing potential).
k) Enter the subject’s PID and body weight in the IRT system for IP kit assignment.
l)
The pharmacist will receive an email with PID, body weight, and kit number.
m) The study pharmacist will prepare study drug using the weight obtained at the visit. The
final combined volume of the IV bag of study drug + 0.9% NaCl will be 120 mL.
Note: 100 mL of the calculated dose of study drug will be administered to the subject.
The extra 20 mL is to be used to prime the IV infusion line during preparation of the IV
line at the bedside or to be left over in the infusion bag.
2)
During the Infusion of Study Drug:
a) Infuse 100 mL of study drug over at least 2 hours using an infusion pump per the
instructions and infusion rate schedule in the Administration of Investigational Product
section of the Pharmacy Manual. 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 infusion.
c) Perform symptom-directed physical exam, as needed.
d) If the subject experiences an IRR that causes an interruption or cessation of the study
drug infusion, a blood sample should be collected within 1–2 hours of the onset of
symptoms for exploratory safety analysis. An unscheduled ADA blood sample may be
obtained if an immunogenicity-related AE is suspected.
3)
Post-Infusion:
a) Subject will remain at the study site for at least 1 hour postdose for observation. In the
event of an IRR, the subject may require prolonged observation (>1 hour or until the
symptoms resolve), as per Investigator discretion.
b) Perform symptom-directed physical exam, as needed.
c) Collect vital signs immediately (+5 minutes) following the end of infusion and 1 hour
(±5 minutes) postdose.
d) Collect CBC with differential 1 hour (±15 minutes) after the end of the infusion.
e) Subject will be instructed to immediately contact the study doctor if any reactions occur
after discharge.


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 8 0  of 1 4 0  
C o nfi de nti al  
1 2. 1 0  D a y 1 4 1 ( ± 3) – D ose 6  
1)
Pre -I nf usi o n:
a)
C o nfir m c o nti n ue d eli gi bilit y.
b) 
 t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
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)
Deter mi ne b o d y w ei g ht.
g)
C ollect vital si g ns.
h) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
i)
C ollect t he f oll o wi n g sa m ples f or t he ce ntral la b orat or y:

C B C wit h differe ntial

C he mistr y

P har mac o ki netics

A nti- dr u g a nti b o dies

Uri nal ysis, if warr a nte d i n t he o pi ni o n of t he I n vesti gat or or S u bi n vesti gat or
j)
Perf or m uri ne pre g na n c y test (if s u bject is of c hil d beari n g p ote ntial).
k) E nter t he s u bject’s PI D a n d b o d y wei g ht i n t he I R T s yste m f or I P kit assi g n me nt.
l)
T he p har macist will recei ve a n e mail wit h PI D, b o d y wei g ht, a n d kit n u m ber.
m)
T he st u d y p har 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 he calc ulate d d ose of st u d y dr u g will be a d mi nistere d t o t he s u bject.
T he e xtra 2 0 m L is t o be use d t o pri me t he I V i nf usi o n li ne d uri n g t he pre parati o n of t he
I V li ne at t he be dsi de or t o be left o ver i n t he i nf usi o n ba g.
2)  
D uri n g t he I nf usi o n of St u d y Dr u g:
a)
I nf use 1 0 0 m L of st u d y dr u g o ver at least 2 h o urs usi n g a n i nf usi o n p u m p per t he
i nstr ucti o ns a n d i nf usi o n rate sc h e d ule i n t he A d mi nistrati o n of I n v esti gati o nal Pr o d uct
secti o n of t he P har mac y Ma n ual. 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.
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 8 1  of 1 4 0  
C o nfi de nti al  
b)
C ollect vital si g ns 1 5 ( ± 5) mi n utes after t he start of i nf usi o n.
c) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
d) If t he s u bject e x p erie n ces a n I R R t hat ca uses a n i nt err u pti o n or cessati o n of t he st u d y
dr u g i nf usi o n, a bl o o d sa m ple s h o ul d be c ollecte d wit hi n 1 – 2 h o urs of t he o nset of
s y m pt o ms f or e x pl orat or y safet y a n al ysis. A n u nsc he d ule d A D A bl o o d sa m ple ma y be
o btai ne d if a n i m m u n o ge nicit y- relate d A E  is s us p ecte d.
3) 
P ost-I nf usi o n:
a)
S u bject will re mai n at t he st u d y site f or at least 1 h o ur p ost d ose f or o bser v ati o n. I n t he
e ve nt of a n I R R, t he s u bj ect ma y re q uire pr ol o n ge d o bser vati o n ( > 1 h o ur or u ntil t he
s y m pt o ms res ol ve), as per I n vesti gat or discreti o n.
b) Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
c)
C ollect vital si g ns i m me diatel y ( + 5 mi n utes) f oll o wi n g t he e n d of i nf usi o n a n d 1 h o ur
( ± 5 mi n utes) p ost d ose.
d) 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.
e)
S u bject will be i nstr ucte d t o i m me diatel y c o ntact t he st u d y d oct or if a n y reacti o ns occ ur
after disc h ar ge.
1 2. 1 1  D a y 1 6 9 ( ± 3) – Wee k 2 4 
1) 
S u bject s h o ul d arri ve f asti n g f or t he E G D pr o ce d ure, as s pecifie d b y i nstr ucti o ns fr o m t he
E G D pr o vi der.
2) 
 t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
3)  
D oc u me nt a n y c h a n ges t o healt h stat us.
4)  
D oc u me nt a n y c h a n ges t o c o nc o mita nt me dic ati o ns.
5)
D oc u me nt a n y c h a n ges t o Baseli ne Diet.
6)  
Deter mi ne b o d y w ei g ht.
7)  
O btai n vital si g ns bef ore bl o o d dra ws.
8) 
Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
9)
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 nt ial
b)
C he mistr y
C CI


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c)
P har mac o ki netics
d)
T otal Ser u m I g E
e)
Bl o o d f or e x pl orat or y a n al ysis
1 0)
Perf or m E G D
a)
Assess a n d gra d e e n d osc o pic se verit y per t h e E R E F S usi n g t he E R E F S Sc ori n g T o ol.
b) Bi o ps y c ollecti o n per t he A K 0 0 2- 0 1 4 Hist ol o g y Ma n ual, Ce ntral La b orat or y Ma n ual,
a n d all E G D f acilit y sta n dar d o perati n g pr oce d ures ( S O P).
1 1) I n v esti gat or t o e val uat e w het her t he s u bject is eli gi ble f or o pti o nal partici pati o n i n t he O L E
peri o d. S u bjects w h o ar e eli gi ble f or a n d c h o os e t o partici pate i n t he O L E p eri o d  will n ot
f oll o w t he E val uati o ns a n d Pr oce d ures b y Visit u n der Secti o ns 1 2. 1 2  a n d 1 2. 1 3 . Be gi n ni n g
o n Da y 1 7 6 ( ± 3), eli gi ble s u bjects w h o c h o ose t o partici pate i n t he O L E p eri o d  will f oll o w
t he O L E Sc he d ule of E ve nts (Ta ble  5) i n A p pe n di x 1 2 .
1 2. 1 2  D a y 1 9 7 ( ± 7) – E n d of St u d y 
1) 
 t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
2)  
D oc u me nt a n y c h a n ges t o healt h stat us.
3)  
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.
4)  
D oc u me nt a n y c h a n ges t o baseli ne diet.
5)  
Deter mi ne b o d y w ei g ht.
6)  
O btai n vital si g ns bef ore bl o o d dra ws.
7) 
Perf or m s y m pt o m- direct e d p h ysi cal e xa m, as nee de d.
8)
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 – bl o o d c o u nts deter mi ne if e xte n de d f oll o w- u p is re q uire d.
b)
C he mistr y
c)
P har mac o ki netics
d)  A nti- dr u g a nti b o dies
e)
Bl o o d f or e x pl orat or y a n al ys is
f)
Uri nal ysis
C CI


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1 2. 1 3  E arl y Ter mi n ati o n 
Perf or m 2 8 ( ± 3) d a ys aft er t he last d ose of st u d y dr u g ( or bef ore, if n ecessar y, t o e ns ure 
c o m plia nce wit h t he visit). If a s u bject disc o nti n ues t he st u d y m ore t ha n 2 8 da ys after t h e last 
d ose of st u d y dr u g, t he E T visit s h o ul d be perf or m e d as s o o n as p ossi ble. 
1)
If e arly ter mi n ati o n occ urs after D ay 2 9 a n d pri or t o D ay 1 6 9, t he s u bject s h o ul d arri ve
fasti n g f or t he E G D pr oce d ure, as s p ecifie d b y i nstr ucti o ns fr o m t he E G D pr o vi der.
2) 
 t o be self- a d mi nistere d b y t he s u bject via t h eir pers o nal electr o nic de vice.
3)  
D oc u me nt a n y c h a n ges t o healt h stat us.
4)  
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.
5)  
D oc u me nt a n y c h a n ges t o baseli ne diet.
6)  
Deter mi ne b o d y w ei g ht.
7)  
O btai n vital si g ns bef ore bl o o d dra ws.
8) 
Perf or m s y m pt o m- direct e d p h ysical e xa m, as nee de d.
9)
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 – bl o o d c o u nts deter mi ne if e xte n de d f oll o w- u p is re q uire d.
b)
C he mistr y
c)
P har mac o ki netics
d)  A nti- dr u g a nti b o dies
e)
T otal Ser u m I g E o nly if e arly ter mi n ati o n occ urs pri or t o D ay 1 6 9
f)
Bl o o d f or e x pl orat or y a n al ysis
g)
Uri nal ysis
1 0)
Perf or m E G D o nly if e arl y ter mi n ati o n occ urs after D ay 2 9 a n d pri or t o D ay 1 6 9 .
a)
Assess a n d gra d e e n d osc o pic se verit y per t h e E R E F S usi n g t he E R E F S Sc ori n g T o ol.
b) Bi o ps y c ollecti o n per t he A K 0 0 2- 0 1 4 Hist ol o g y Ma n ual, Ce ntral La b orat or y Ma n ual,
a n d all E G D f acilit y S O P.
1 2. 1 4  E xte n de d F oll o w- U p  
S u bjects m ust ret ur n t o t he site e ver y 2 8 ( ± 3) da ys t o m o nit or a bs ol ute l y m p h oc yte a n d 
e osi n o p hil c o u nts u ntil rec o ver y. D ata c ollecte d d uri n g e xte n de d f oll o w- u p will be li mite d t o:  
C CI


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1)
CBC with differential
2)
Adverse events of special interest
3)
Serious adverse event
13.
Adverse Event Reporting and Documentation
13.1 
Adverse Events 
In accordance with 21 Code of Federal Regulation (CFR) 312.32(b) and International 
Conference on Harmonisation (ICH) Guidance E2A, an adverse event is any untoward medical 
occurrence in a clinical investigation of a subject administered a pharmaceutical product and that 
does not necessarily have a causal relationship with the treatment. An AE is therefore any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the administration of an investigational product, whether or 
not related to that investigational product. An unexpected AE is one of a type not identified in 
nature, severity, or frequency in the current Investigator’s Brochure or of greater severity or 
frequency than expected based on the information in the Investigator’s Brochure.  
Examples of an AE include: 
•
Significant worsening or exacerbation of an underlying medical condition.
•
Significant abnormal findings from physical exams, vital signs, or laboratory tests.
The following examples are not considered an AE: 
•
Medical or surgical procedure, although the condition leading to the procedure is usually an
AE.
•
Anticipated day-to-day fluctuations of preexisting medical conditions (including laboratory
values) as long as significant worsening from Baseline does not occur.
•
Signs or symptoms of the disorder being studied unless they become more severe or occur
with a greater frequency than occurring at Baseline.
All AE, whether elicited by questions from study staff, volunteered, or noted on physical 
examination/laboratory testing, and regardless of causality or severity, will be assessed and 
recorded in the eCRF beginning after first administration of study drug and ending at the time of 
the Day 197 visit, the Day 372 visit (for subjects participating in the OLE period), or the ET 
visit, unless otherwise directed by Allakos. For subjects participating in the OLE period, AE will 
be assessed and recorded in the CRF of the AK002-014 treatment period database up until the 
start of the first open-label infusion during the Day 176 visit and recorded in the CRF of the 


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AK002-014 OLE period database beginning from the start of the first open-label infusion during 
the Day 176 visit. 
13.2 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an AE that meets one of the following criteria: 
•
Death
•
A life-threatening AE that places the subject at risk of death at the time of the event. It does
not refer to an event that hypothetically might cause death if it were more severe.
•
Inpatient hospitalization or prolongation of existing hospitalization.
•
A persistent or significant disability/incapacity.
•
A congenital anomaly/birth defect occurring in the offspring of a study subject.
•
Other important medical events may also be considered an SAE when, based on appropriate
medical judgment, they jeopardize the subject or require intervention to prevent one of the
outcomes listed above.
SAE will be assessed and recorded after the first administration of study drug and ending at the 
time of the Day 197 visit, the Day 372 visit (for subjects participating in the OLE period), the 
ET visit, or the last Extended Follow-Up visit (if applicable), unless otherwise directed by 
Allakos. If an SAE that occurs during the screening period (after consent and before the first 
administration of study drug) is assessed to be related to a screening procedure, it will also be 
recorded.  
13.3 
Adverse Events of Special Interest  
Adverse events of special Interest (AESI) for this study include: 
•
Malignancies confirmed by histopathological report. (Mast cells and eosinophils are part of
the normal immune response. By decreasing their function, AK002 could theoretically
increase the risk of malignancy.)
•
Parasitic infections confirmed by positive clinical laboratory test. (Eosinophils are
especially active in protecting the body from parasitic infections and decreasing their
function could theoretically increase the risk of parasitic and opportunistic infections.)
•
Opportunistic infections (infections known to be more severe or occur more frequently in
immunosuppressed populations) as confirmed by positive clinical laboratory test.
•
Infusion-related reactions and hypersensitivity reactions including anaphylaxis.


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Beginning from the time of first study drug infusion and ending at the time of the Day 197 visit, 
the Day 372 visit (for subjects participating in the OLE period), the ET visit, or the last extended 
follow-up visit (if applicable), any new AESI (or new information related to a previously 
reported AESI) must be recorded in the Adverse Event eCRF and designated as an “adverse 
event of special interest.”  
For subjects participating in the OLE period, AESI will be assessed and recorded in the CRF of 
the AK002-014 treatment period database up until the start of the first open-label infusion during 
the Day 176 visit and recorded in the CRF of the AK002-014 OLE period database beginning 
from the start of the first open-label infusion during the Day 176 visit. 
13.4 
Infusion-Related Reactions 
All AE considered by the Investigator to be related to the infusion of the biological substance 
and occurring within 24 hours of the start of the study drug infusion should be captured as 1 IRR. 
Common symptoms of IRR include but are not exclusive to:  
•
Flushing
•
Nausea
•
Chills
•
Vomiting
•
Back or abdominal pain
•
Sweating
•
Chest discomfort or tightness
•
Fever
•
Dizziness
•
Urticaria
•
Shortness of breath
•
Pruritus
•
Headache
•
Bronchospasm
•
Hypotension or hypertension
All symptoms experienced by a subject during an IRR will be listed in the eCRF under 1 IRR, 
unless the Investigator believes a symptom is not part of the IRR, in which case it will be 
recorded separately. The start time of the IRR will be captured as the start time of the first 
symptom, and the end time of the IRR will be captured as the end time of the last symptom.  
If the subject experiences an IRR that causes an interruption or cessation of the study drug 
infusion, a blood sample should be collected within 1–2 hours of the onset of symptoms for 
exploratory safety analysis.  
Subjects will remain at the site for at least 1 hour of observation after each dose. If the subject 
experiences an IRR, prolonged observation (greater than 1 hour or until the symptoms resolve) 


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may be required, as per Investigator discretion. Subjects will also be instructed to immediately 
contact the study doctor if any reactions occur after discharge. 
13.5 
Anaphylaxis 
A suspicion of anaphylaxis will be carefully monitored and treated according to standard of care. 
Emergency crash cart equipment and medications including multiple doses of epinephrine, 
vasopressors, and bronchodilators will be available at all times during the conduct of the study. 
To define anaphylactic reactions in a consistent and objective manner, all AE of suspected 
anaphylaxis will be evaluated using Sampson’s Criteria for Anaphylaxis (Appendix 10). The 
assessment of an AE will be done pursuant to definitions set forth by ICH Good Clinical Practice 
guidelines and applicable regulatory requirements.  
If a subject experiences signs or symptoms of anaphylaxis, the subject may be treated with 
standard of care such as diphenhydramine, acetaminophen, methylprednisolone, epinephrine, and 
other supportive measures along with cessation of the infusion. 
13.6 
Evaluating Adverse Events and Serious Adverse Events 
13.6.1 
Establishing Diagnosis 
Whenever possible, diagnoses should be given when signs and symptoms are due to a common 
etiology (e.g., dysuria, urinary nitrites should be reported as a urinary tract infection). If the 
diagnosis is not known, individual signs and symptoms should be assessed and recorded in the 
Adverse Event eCRF as separate AE. The Investigator (or qualified Subinvestigator) must assign 
the following AE attributes listed below and is responsible for ensuring their capture 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 National 
Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0 or 
most current version) (Table 2 and Appendix 8) to assess the intensity of each AE and SAE. 


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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 version 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 adverse event is not necessarily a 
serious adverse event (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. 
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.  


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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.  
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.  


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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 Adverse Event eCRF 
beginning from the time of first study drug infusion and ending at the time of the Day 197 visit, 
the Day 372 visit (for subjects participating in the OLE period), or the ET visit, unless otherwise 
directed by Allakos. For subjects participating in the OLE period, AE will be assessed and 
recorded in the CRF of the AK002-014 treatment period database up until the start of the first 
open-label infusion during the Day 176 visit and recorded in the CRF of the AK002-014 OLE 
period database beginning from the start of the first open-label infusion during the Day 176 visit. 
Serious adverse events considered related to screening procedures will be recorded in the 
Adverse Event eCRF starting on the date of informed consent. Only AESI and SAE will be 
recorded in the Adverse Event eCRF during extended follow-up, if applicable. Whenever 
appropriate, the CTCAE (v. 5.0 or most current version) should be utilized for naming common 
AE (Appendix 8). 
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.  
Serious adverse event 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. The SAE must also be recorded on the Adverse Event eCRF and designated 
as “serious.”  
Even when only minimal information is available for the initial SAE report, the Investigator 
should try to make a causality assessment, as the causality is used to determine the timing of 
regulatory reporting requirements. If the Investigator or designee is not available to sign the SAE 
report upon initial submission they should be contacted via telephone and their assessment 
documented on the SAE form (with a note stating signature is forthcoming). The Investigator 
may change the causality assessment based on follow-up information and submit an amended 
SAE report form.  


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All efforts will be made to obtain accurate and complete medical records for the SAE. All efforts 
to obtain information should be documented in the subject source document. The site will notify 
the Institutional Review Board (IRB) according to its guidelines.  
The subject’s condition will be followed by the Investigator or designated Subinvestigator until 
resolution of the condition or a return to baseline levels. If additional visits are required, the 
subject will be asked to return to the study site for further follow-up. If the condition is still 
ongoing at the time the subject exits the study, every effort will be made to continue to follow up 
with the subject for a reasonable period of time, as determined by the Investigator or until there 
is a return to Baseline or stabilization of the condition. As additional information becomes 
available, such as hospital discharge notes and patient medical records, the Investigator will be 
notified and provided with all relevant information.  
All SAE that have not resolved by the end of the study or that have not resolved on 
discontinuation of the subject’s participation in the study must be followed until any of the 
following occurs:  
•
The event resolves.
•
The event stabilizes.
•
The event returns to Baseline if a baseline value is available.
•
The event can be attributed to agents other than the investigational product or to factors
unrelated to study conduct.
•
It becomes unlikely that any additional information can be obtained (subject’s or health
care practitioner’s refusal to provide additional information, lost to follow-up after
demonstration of due diligence with follow-up efforts).
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 subjects or in the sexual partners of male 
subjects from the time the subject is first exposed to the investigational product through Day 141 
(±3 days), Day 316 (for subjects participating in the OLE period), or ET.  


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Female subjects must be instructed to discontinue all study drugs and inform the Investigator 
immediately if they become pregnant during the study. Male subjects must be instructed to 
inform the Investigator immediately if their partner becomes pregnant during the study. 
The Investigator must report any pregnancy to Allakos within 24 hours of becoming aware of it 
using the provided pregnancy reporting forms. Female subjects must be immediately 
discontinued from study drug. An uncomplicated pregnancy will not be considered an AE or 
SAE, but all pregnancies will be followed through term.  
Any congenital abnormalities noted at birth in the offspring of a subject who received study drug 
will be reported as an SAE. 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 
Adverse Events of Special Interest Reporting 
Beginning from the time of first study drug infusion and ending at the time of the Day 197 visit, 
the Day 372 visit (for subjects participating in the OLE period), the ET Visit, or the end of the 
Extended Follow-Up period (if applicable), any new AESI (or new information related to a 
previously reported AESI) must be recorded in the Adverse Event eCRF and designated as an 
“adverse event of special interest.”  
For subjects participating in the OLE period, AESI will be assessed and recorded in the CRF of 
the AK002-014 treatment period database up until the start of the first open-label infusion during 
the Day 176 visit and recorded in the CRF of the AK002-014 OLE period database beginning 
from the start of the first open-label infusion during the Day 176 visit. 
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. AESI that are also SAE must be recorded in the Adverse Event 
eCRF and designated as both “serious” and 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. 
13.8 
Medical Monitoring 
The Primary Medical Monitor or the Backup Medical Monitor should be contacted directly using 
the phone number and/or email address below to report medical concerns or for questions 
regarding safety. 


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Pa ge 9 3  of 1 4 0  
C o nfi de nti al  
All a k os A K 0 0 2- 0 1 4 Me dic al M o nit or s 
 MD  
 M D 
Pri mar y Me dical M o nit or  
Bac k u p Me dical M o nit or 
P h o ne: 
 
P h o ne: 
 
E mail:  
 
E mail:  
 
1 3. 9  
I n de pe n de nt D at a M o nit ori n g C o m mittee 
A n i n de pe n de nt D ata M o nit ori n g C o m mittee (i D M C) has bee n c o n v e ne d f or t his st u d y. T he 
i D M C will meet at esta blis he d i nter vals 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 r e vie ws.  
1 3. 1 0  St u d y Wit h dr a w al Criteri a  
Partici pati o n  of a s u bject will be disc o nti n ue d i n t he e ve nt t hat: 
•
Occ urre nce of a n e xcl usi o n criteri o n, w hic h is cli nicall y rele va nt a n d affects t he s u bject’s
safet y, if disc o nti n uati o n is c o nsi dere d necessar y b y t he I n v esti gat or a n d/ or S p o ns or.
•
Re b o u n di n g of e osi n o p hil c o u nts t o > 1 5 0 0/ µ L i n s u bjects w h o e ntere d t he st u d y wit h
e osi n o p hil le vels > 1 5 0 0/ µ L a n d w h 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 dra 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 testi n g) wit h o ut a n alter nati ve e x pl a nati o n.
•
Ele vati o n of A L T or A S T > 3 × U L N (c o nfir me d b y re peat testi n g) wit h t h e a p peara n ce or
w orse ni n g of s y m pt o ms t hat t he I n vesti gat or belie ves t o be p ote ntiall y relat e d t o he patic
i nfla m mati o n s uc h as fati g ue, na usea, v o miti n g, ri g ht u p per q ua dra nt pai n or te n der n ess,
fe ver, or 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 be disc o nti n ue d pre mat urel y i n t he e ve nt of a n y of t he f oll o wi n g: 
•
A life -t hreate ni n g A E  t hat is p ossi bl y or pr o ba bl y relate d t o treat 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 lea di n g t o a n u nfa v ora ble ris k- b e 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
P P D
P P D


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Health Authorities and IRB will be informed about the discontinuation of the trial in accordance 
with applicable regulations. The trial may be terminated or suspended on request of Health 
Authorities or Sponsor. 
14.
Discontinuation and Replacement of Subjects
14.1 
Definition of Study Completion 
A subject who does not participate in the OLE period and who completes visits through the 
Day 197 visit or, if applicable, the last Extended Follow-Up visit after completing Day 197, will 
be recorded as having completed the double-blind portion of the study. 
A subject who completes visits through the Day 169 visit and participates in the OLE period of 
the study will be recorded as having completed the double-blind portion of the study. 
A subject who participates in the OLE period of the study and completes visits through the 
Day 372 visit or, if applicable, the last Extended Follow-Up visit after completing Day 372, will 
be recorded as having completed the OLE portion of the study. 
14.2 
Early Discontinuation of Study Drug 
A subject may be discontinued from study treatment at any time if the subject, the Investigator, 
or the Sponsor believes that it is not in the subject’s best interest to continue. The following is a 
list of possible reasons for study treatment discontinuation: 
•
Subject withdraws consent.
•
Adverse event that in the opinion of the Investigator results in study treatment
discontinuation being in the best interest of the subject.
•
Protocol violation requiring discontinuation of study treatment.
•
Participation in any other study during the duration of this study.
•
Use of a non-permitted concomitant drug without prior approval from the Medical Monitor.
•
Loss of ability to freely provide consent through imprisonment or involuntary incarceration
or treatment of either a psychiatric or physical (e.g., infectious disease) illness.
If a subject is withdrawn from treatment due to an AE, the subject will be followed and treated 
by the Investigator until the abnormal parameter or symptom has resolved or stabilized.  
All subjects who discontinue study drug treatment should be encouraged to continue on study 
and complete assessments and procedures according to the follow-up period in Table 1, if 
possible (including follow-up EGD).  


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Reasonable attempts will be made by the Investigator to provide reasons for subject withdrawals. 
The reason for the subject’s withdrawal from the study, or all attempts to acquire such, will be 
specified in the source documents.  
Enrolled subjects who discontinue the study early will not be replaced. 
15.
Statistical Methods
15.1 
General Considerations 
This section outlines the nature and rationale for the statistical methods to be used for the 
analysis of the data from the study. A separate Statistical Analysis Plan (SAP), which will be 
documented as completed prior to unblinding the study, will describe data handling and 
statistical techniques in detail and will supersede the statistical methods described 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 observation before the first 
IV infusion of the study drug. All subject data will be listed for the double-blind placebo-
controlled portion of the study. When appropriate, summary statistics of number of non-missing 
values, mean, median, standard deviation, minimum, and maximum will be computed for 
continuous variables, and summary statistics of number and proportion will be computed for 
categorical variables. Two-sided 95% confidence intervals will be provided for the mean and 
proportion. No formal statistical inferences will be made for safety parameters.  
Unless otherwise specified, safety data will be summarized for each treatment group as well as 
for the 2 active dose groups combined. 
Statistical analysis will be performed upon completion of the double-blind, placebo-controlled 
portion of the study. On completion of the OLE period, additional statistical analyses will be 
performed on data collected in that period and for the entirety of the study. 
15.2 
Sample Size 
To achieve statistical significance for the first co-primary endpoint, a sample size of 8 subjects 
per treatment group will provide 90% power to demonstrate a statistically significant difference 
between any AK002 dose regimens and placebo in achieving histological response (defined as 
≤6 eosinophils/hpf at Week 24). This calculation is based on the AK002-003 study in which 90% 
of AK002 subjects and 10% of placebo subjects achieved a histologic response at Day 99. The 
hypothesized treatment effect of 80% yielded a small number of subjects per group for the first 
co-primary endpoint. 


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To achieve statistical significance for the second co-primary endpoint, a sample size of 
86 subjects per treatment group will provide 90% power to demonstrate a statistically significant 
difference between any AK002 dose group and placebo group in mean absolute change in DSQ 
score from Baseline to Weeks 23–24. This calculation is based on the baseline score of 30 ± 15 
(mean ± SD) reported in the literature, and an expected mean reduction of 15 in the AK002 
group and 7.5 in the placebo group, and a SD of 15 for the change from baseline (Dellon, 2017; 
Hirano, 2019; Hudgens, 2017). 
Consequently, approximately 100 subjects per treatment group will be included for a total of 
300 subjects, driven by the second co-primary endpoint and a potential dropout rate of 14%. 
15.3 
Data Sets Analyzed 
All subjects who have received study medication will be included in the Safety population for 
safety analysis. Subjects who are randomized and have received at least 1 dose of study 
medication will be included in the Modified Intent-to-Treat (MITT) population for efficacy 
analysis. Subjects who meet MITT criteria and do not have significant protocol deviations 
interfering with efficacy assessment will be included in the Per Protocol (PP) population. The 
study statistician along with the study team will review protocol deviations to identify subjects to 
be excluded from the PP analysis population. The MITT population will be used for all efficacy 
analysis, and the PP population will be used for supplementary analyses of the primary endpoints 
and select secondary endpoints. 
15.4 
Subject Disposition 
The number and percent of subjects who complete or discontinue from the study will be 
summarized. The reasons for study discontinuation will be included in the summary.  
15.5 
Demographic and Baseline Characteristics 
The following demographic and baseline variables will be summarized: 
•
Demographics
•
Medical history
•
Complete physical exam
•
ECG at screening
•
Screening vital signs and laboratory tests
15.6 
Study Drug Exposure 
Number and percent (n and %) of subjects who have received a maximum of 1, 2, 3, 4, 5, and 6 
infusions will be presented. 


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15.7 
Efficacy Analysis 
A hierarchical procedure will be used to control the overall Type I error rate at 0.05 for the 
primary endpoint and the secondary endpoints across the 2 AK002 dose regimens versus 
placebo. Each hypothesis will be formally tested only if the preceding hypothesis is significant at 
the 2-sided 0.05 significance level. The hierarchical testing order (all comparisons are with the 
placebo) is detailed in the SAP. 
15.7.1 
Primary Efficacy Endpoint Analysis 
The first co-primary endpoint is the proportion of subjects who achieve a peak esophageal 
intraepithelial count of ≤6 eosinophils/hpf at Week 24. The endpoint will be analyzed using 
Fisher’s exact test comparing the AK002 group and placebo group for the proportion of 
treatment responders. Subjects who experience an ICE (e.g., exit the study prematurely or initiate 
prohibited/rescue medication or therapeutic EGD procedure) prior to the end of Week 24 will be 
treated as non-responders.  
The second co-primary endpoint is the mean change in DSQ score from Baseline to 
Weeks 23-24. The DSQ score will be analyzed using ANCOVA with treatment as a factor, and 
Baseline DSQ and age strata (12-17, ≥18) as covariates. The Baseline DSQ will be calculated 
using the DSQ scoring algorithm for all daily DSQ assessments collected during the 2 weeks 
prior to the first infusion of study drug.  
Data on subjects who experience an ICE (e.g., exit the study prematurely or initiate 
prohibited/rescue medication or therapeutic EGD procedure) prior to the end of Week 24 will be 
set to missing. Missing DSQ will be imputed using the Markov Chain Monte Carlo (MCMC) 
method.  
Two sensitivity analyses will be conducted for the second co-primary endpoint. 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 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 utilize the tipping point method. In this method, the missing biweekly 
DSQ 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).  


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Change in continuous outcomes will be analyzed using a mixed model for repeated measures 
(MMRM) and will include fixed effects for baseline value, treatment, week. and the treatment-
by-week interaction and allow for random subject effects. Treatment and week will each be fitted 
as categorical variables. Model will assume unstructured covariance structure. If the model with 
unstructured covariance does not converge or it is determined to be inappropriate as outlined in 
the Guerin and Stroup study, (Guerin, 2000), then other covariance structures will be considered 
to model the within-subject errors. The selection of the covariance structure for the final model 
will be handled in a hierarchical fashion with the order being heterogeneous Toeplitz, AR(1), 
and compound symmetry, respectively. 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. The LSM with 95% CI will be presented for each 
treatment*week cross-classification.  
15.7.2 
Secondary Efficacy Endpoint Analysis 
The percent change in peak esophageal intraepithelial eosinophil count at Week 24 will be 
analyzed using ANCOVA with treatment as a factor and baseline eosinophil counts, baseline 
DSQ, and age strata as covariates. The LSM, SE, and 95% CI for individual treatment groups, 
and the LSM, SE, 95% CI, and p-value for the between treatment difference will be presented. 
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of 
≤1 eosinophil/hpf at Week 24 will be analyzed using Fisher’s exact test.  
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of 
<15 eosinophil/hpf at Week 24 will be analyzed using Fisher’s exact test. 
Proportion of Treatment Responders, defined by subjects with ≥30% improvement in DSQ score 
at Weeks 23–24 and a peak esophageal intraepithelial eosinophil count of ≤6 eosinophils/hpf  at 
Week 24, will be analyzed using Fisher’s exact test. 
Proportion of subjects with >50% reduction in DSQ score from Baseline to Weeks 23–24 will 
be analyzed using the Cochran-Mantel-Haenszel (CMH) test. The randomization stratum (age 
and baseline DSQ) will be used as the stratification factor for the analysis. 
Change in DSQ scores from Baseline to Weeks 23–24 will be analyzed using MMRM and will 
include fixed effects for age, baseline DSQ, treatment, visit, treatment-by-visit interaction, and 
allow for random subject effects.  
The analysis of change in biweekly mean DSQ over time will employ MMRM similarly as 
described above.  


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Change in EoE Reference Score for Endoscopic Abnormalities from Baseline will be 
summarized and analyzed using MMRM with age, treatment, visit, and treatment-by-visit 
interaction as fixed factors and baseline peripheral blood eosinophil count and baseline DSQ 
(continuous) as covariates. 
15.7.3 
Exploratory Endpoint Analysis 
Change in continuous exploratory endpoints will be analyzed using MMRM and will include 
fixed effects for age, baseline value, treatment, visit, and treatment-by-visit interaction and allow 
for random subject effects. Treatment and visits will be fitted as categorical variables. 
15.8 
Safety Analysis  
Adverse Events: All AE will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be classified by MedDRA system organ class (SOC) and preferred term. 
Listings will include all AE collected on study. The summaries of AE will be based on TEAE, 
defined as an AE reported in the clinical database with a date of onset (or worsening) on or after 
the start date of the first IV infusion of the study medication.  
Subject incidence (N and %) of TEAE will be summarized as follows: 
•
Overview of TEAE will include:
−
Number (%) of subjects who reported at least 1 TEAE overall, by maximum severity,
and by strongest relationship
−
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 preferred term in descending order of subject incidence
•
TEAE by SOC and preferred term
•
TEAE by maximum severity, SOC, and preferred term
•
Drug-related TEAE by SOC and preferred term
•
TEAE leading to treatment discontinuation by SOC and preferred term
•
Serious TEAE by SOC and preferred term
•
TEAESI by SOC and preferred term


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Clinical Laboratory Assessments: Descriptive statistics will be used to summarize hematology, 
chemistry, and urinalysis 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. Number (and %) of subject incidence of 
positive ADA tests will be summarized. 
Vital Signs: Vital signs will be summarized at Baseline, each visit, and change from Baseline at 
each visit.  
ECG: Subject incidence of the Investigator’s overall assessment (normal, abnormal – not 
clinically significant, and abnormal – clinically significant) will be summarized. 
Physical Exam: New or worsening symptoms in the symptom-directed physical exams will be 
included in the by-subject data listing.  
Prior and Concomitant Medications: All medications (prior and concomitant) will be coded 
using the most current World Health Organization Drug Dictionary (WHODD). Prior and 
concomitant medications will be summarized with subject and percent incidence by Anatomical 
Therapeutic Chemical Class and preferred term.  
15.9 
Subject Confidentiality 
Subject identity should be confirmed by the presentation of a photo identification to ensure the 
correct individual is consented, screened, and enrolled (if eligible).  
Only the PID, subject initials, and demographics will be recorded in the eCRF to the extent 
allowed by country requirements. If the subject name appears on any source document collected 
(e.g., hospital discharge summary), it must be removed from the document if the document will 
be viewed by the Sponsor or a sponsor-contracted study vendor not permitted access to subject 
identifying information.  
All study findings will be stored in electronic databases. The subjects 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. Subjects will be informed that all personal 
information made available for inspection will be kept confidential to the extent permitted by all 
applicable state, local, and federal data protection/privacy laws and/or regulations and will not be 
made publicly available. If the results of the trial are published, the subject’s identity will remain 
confidential. At study check-in to the study site, subjects will be advised not to share their study 
information with other subjects.  


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16.
Data Collection, Retention, and Monitoring
16.1 Data Collection Instruments  
All staff at participating clinical sites will adhere to good documentation practices. Data will be 
entered into eCRFs using source document data. Source documents may include but are not 
limited to laboratory data, recorded data from automated instruments, medical progress notes, 
and email correspondence.  
16.2 
Data Management Procedures  
The data will be entered into a validated database. The Data Management group will be 
responsible for data processing in accordance with procedural documentation. Database lock will 
occur once quality assurance procedures have been completed.  
All procedures for handling and analysis of data will be conducted using good computing 
practices meeting Food and Drug Administration (FDA) guidelines for handling and analysis of 
data for clinical trials.  
16.3 
Data Quality Control and Reporting  
After data have been entered into the study database, a system of computerized data validation 
checks will be implemented and applied to the database on a regular basis. Queries are entered, 
tracked, and resolved through the EDC system directly. The study database will be updated in 
accordance with the resolved queries, and all changes to the study database will be documented. 
16.4 
Database Lock/Disclosure of Randomization Code 
There will be 2 database locks for the double-blind treatment period of the study: 
•
A provisional database lock after all subjects complete the Day 169 study 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.
For each database lock, applicable EDC data will be locked in order to protect write access after 
the following preconditions are fulfilled: 
•
All subjects have completed their participation in the double-blind portion of the study.
•
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.


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•
All data queries have been resolved.
•
All decisions have been made regarding all protocol violations and ITT population
exclusions.
•
Written authorization to lock the database is 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. The study will
remain blinded to the study sites and Allakos Medical Monitors, Allakos Study Monitors,
and Allakos Clinical Data Management until after the final database lock.
16.5 
Archiving of Data 
The database is safeguarded against unauthorized access by established security procedures; 
appropriate backup copies of the database and related software files will be maintained. 
Databases are backed up by the database administrator in conjunction with any updates or 
changes to the database.  
At critical junctures of the protocol (e.g., production of interim reports and final reports), data for 
analysis is locked and cleaned per established procedures.  
16.6 
Availability and Retention of Investigational Records 
In accordance with 21 CFR 312.62(c), GCP, and all other applicable regulatory requirements, 
following completion or termination of the study, the Sponsor or designee will retain a copy of 
all study records in a limited access storage room for a minimum of 2 years after notification that 
the investigations have been discontinued and the FDA has been notified, or for 2 years after all 
marketing applications have been approved. The trial master file will be created during the 
implementation phase of a study, maintained on an ongoing basis throughout the duration of the 
project, and collated at the end of the study. The files will contain folders that may include but 
are not limited to the following subcategories: 
•
Financial agreements
•
Regulatory documents
•
Independent Ethics Committee/Institutional Review Board Documents
•
Drug Accountability
•
Correspondence


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•
Medical Reports
•
Subject Data
•
Monitoring Visit Reports
•
Sample CRF and CRF Guidelines
16.7 
Monitoring 
Monitoring visits will be conducted by representatives of the Sponsor according to 21 CFR 
Parts 50, 56, and 312 and ICH GCP Guideline E6. By signing this protocol, the Investigator 
grants permission to the Sponsor (or designee), and appropriate regulatory authorities to conduct 
on-site and remote monitoring and/or auditing of all appropriate study documentation. Due to the 
coronavirus pandemic, some monitoring may be performed remotely rather than on site. 
17.
Administrative, Ethical, and Regulatory Considerations
The study will be conducted in a manner consistent with the Declaration of Helsinki, Protection
of Human Volunteers (21 CFR 50), Institutional Review Board (21 CFR 56 and ICH E6), and
Obligations of Clinical Investigators (21 CFR 312 and ICH E6). The Investigator must also
comply with all applicable privacy regulations (e.g., HIPAA, European Union Data Protection
Directive 95/46/EC).
17.1 
Protocol Amendments  
An amendment must be agreed to in writing by Allakos Inc. and submitted to the health authority 
as a Clinical Trial Application/Investigational New Drug (IND) amendment. Protocol 
amendments cannot be implemented without prior written IRB approval except as necessary to 
eliminate immediate safety hazards to subjects. Written approval of a protocol amendment is not 
required prior to implementation of changes to the protocol that eliminate immediate hazard to 
the subject; however, approval must be obtained as soon as possible thereafter. Any protocol 
amendments must also be signed by the Investigator.  
17.2 
Independent Ethics Committee/Institutional Review Board  
The protocol and ICF will be reviewed and approved by the Independent Ethics Committee 
(IEC) and/or Institutional Review Board (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 IEC/IRB in accordance with the standard 
operating procedures and policies of the IEC/IRB, and the Investigator will keep the IEC/IRB 
informed as to the progress of the study. The Investigator will obtain assurance of IEC/IRB 
compliance with regulations.  


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Any documents that the IEC/IRB may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, ICF, information concerning subject recruitment, 
payment or compensation procedures, or other pertinent information) will be submitted to the 
IEC/IRB. The IEC/IRB written unconditional approval of the study protocol and the ICF will be 
in the possession of the Investigator before the study is initiated. The IEC/IRB 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 the 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 the subjects or the conduct of the study; an annual update and/or request for 
re-approval; and when the study has been completed.  
17.3 
Informed Consent Form 
Prior to study enrollment, all subjects must consent to participate. In accordance with ICH GCP 
Guideline E6, subjects should be asked whether they would like their primary care physician 
notified of their study participation. If yes, the physician will be notified in writing. Otherwise, 
the subject should sign a form stating that he/she does not wish to disclose such information. The 
process of obtaining informed consent will comply with all federal regulations, ICH 
requirements, and local laws.  
The Investigator or a designee will review the study and the ICF with each potential subject. 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 subject. The 
Investigator or designee and the subject must both sign and date the ICF after review and before 
the subject can participate in the study. The subject will receive a copy of the signed and dated 
form, and the original will be retained in the site’s study files. The Investigator or designee must 
emphasize to the subject 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 
subject is otherwise entitled.  
In addition, prior to undergoing biopsies, subjects will provide informed consent in accordance 
with the standard operating procedures and policies of the EGD facility/investigational sites.  


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17.4 
Publications 
The preparation of manuscripts containing the study results and submittal for publication shall 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 shall comply with all 
applicable privacy laws including but not limited to the Health Insurance Portability and 
Accountability Act (HIPAA) of 1996.  
17.5 
Clinical Study Registration 
This clinical study is registered on the Clinical Trial Registry Website, www.ClinicalTrials.gov, 
as NCT #04322708. 
17.6 
Payment to Subjects 
All subjects may be compensated for participating in this study in accordance with the payment 
amounts per study day stated in the subject’s signed ICF approved by the IRB. If the subject is 
discontinued from the study prior to the last study visit, the subject will be compensated for each 
completed study visit on a pro rata basis, as stated in the subject’s ICF. Subjects 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 form, 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 IEC/IRB review
and approval meet federal guidelines.
4)
Report to the Sponsor or designee any AE that occur in the course of the study, in
accordance with 21 CFR Part 312.64 and ICH Guideline E2A.
5)
Ensure that all associates, colleagues and employees assisting in the conduct of the study
are informed about their obligations in meeting the above commitments.
6)
Maintain adequate and accurate records in accordance with 21 CFR Part 312.62 and ICH
Guideline E6 and to make those records available for inspection with the Sponsor (or
designee).


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


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18.
References
Abonia J, Blanchard C, Buckmeier-Butz B, Rainey H, Collins M, Stringer K, et al. Involvement
of mast cells in eosinophilic esophagitis. Journal of Allergy and Clinical Immunology, 
2010;126:140–49. 
Arias A, González-Cervera J, Tenias J, Lucendo A. Efficacy of dietary interventions for inducing 
histologic remission in patients with eosinophilic esophagitis: A systematic review and 
meta-analysis. Gastroenterology, 2014;136:1639–48. 
Assa’ad A, Gupta S, Collins M, Thomson M, Heath A, Smith D, et al. An antibody against IL-5 
reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic 
esophagitis. Gastroenterology, 2011;141:1593-1604. 
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;39:317–24. 
Clayton F, Fang J, Gleich G, Lucendo A, Olalla J, Vinson L, et al. Eosinophilic esophagitis in 
adults is associated with IgG4 and not mediated by IgE. Gastroenterology, 
2014;147:602–09. 
Collins M, Capocelli K, Yang G. Eosinophilic gastrointestinal disorders pathology. Frontiers in 
Medicine, 2018;4:261.1–8. 
Dellon E. Epidemiology of eosinophilic esophagitis. Gastroenterol Clin North Am, 
2014;43:201–18. 
Dellon E, Speck O, Woodward K, Covey S, Rusin S, Gebhart J, et al. Markers of eosinophilic 
inflammation for diagnosis of eosinophilic esophagitis and proton pump inhibitor-
responsive esophageal eosinophilia: A prospective study. Clin Gastroenterol Hepatol, 
2014;12:2015–22. 
Dellon E, Veerappan R, Selitsky S, Parker J, Higgins L, Beitia R, et al. A gene expression panel 
is accurate for diagnosis and monitoring treatment of eosinophilic esophagitis in adults. 
Clin Transl Gastroenterol, 2017;8:e74.1–8. 
Dellon E, Liacouras C, Molina-Infante J, Furuta G, Spergel J, Zevit N, et al. Updated 
international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of 
the AGREE Conference. Gastroenterology, 2018;155:1022–33. 
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. 


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Furuta G, Atkins F, Lee N, Lee J. Changing roles of eosinophils in health and disease. Ann 
Allergy Asthma Immunol, 2014;113:3-8. 
Furuta G, Katzka D. Eosinophilic Esophagitis. N Engl J Med, 2015;373:1640-48. 
Guerin L, Stroup W. A simulation study to evaluate PROC MIXED analysis of repeated 
measures data. Conference on Applied Statistics in Agriculture, 12th annual conference 
proceedings, 2000.  
Hirano I, Collins M, Assouline-Dayan Y, Evans L, Gupta S, Schoepfer A, et al. RPC4046, a 
monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients 
with eosinophilic esophagitis. Gastroenterology, 2019;156:592–603. 
Hirano I, Schoepfer A, Comer G, Safroneeva E, Meltzer B, Falk G. A randomized, double-blind, 
placebo-controlled trial of a fluticasone propionate orally disintegrating tablet in adult 
and adolescent patients with eosinophilic esophagitis: A Phase 1/2A safety and 
tolerability study. Gastroenterology, 2017;152:S195. 
Hudgens S, Evans C, Phillips E, Hill M. Psychometric validation of the Dysphagia Symptom 
Questionnaire in patients with eosinophilic esophagitis treated with budesonide oral 
suspension. Journal of Patient-Reported Outcomes, 2017;1:3.1–11. 
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. 
Konikoff M, Noel R, Blanchard C, Kirby C, Jameson S, Buckmeier B, et al. A randomized, 
double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic 
esophagitis. Gastroenterology, 2006;131:1381-91. 
Lucendo A, Arias Á, González-Cervera J, Yagüe-Compadre J, Guagnozzi D, Angueira T, et al. 
Empiric 6-food elimination diet induced and maintained prolonged remission in patients 
with adult eosinophilic esophagitis: a prospective study on the food cause of the disease. 
J Allergy Clin Immunol, 2013;131:797–804. 
Markowitz J, Jobe L, Miller M, Frost C, Laney Z, Eke R. Safety and efficacy of reslizumab for 
children and adolescents with eosinophilic esophagitis treated for 9 years. J Pediatr 
Gastroenterol Nutr, 2018;66:893–97. 


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Molina-Infante J, Bredenoord A, Cheng E, Dellon E, Furuta G, Gupta S, et al. Proton pump 
inhibitor-responsive oesophageal eosinophilia: An entity challenging current diagnostic 
criteria for eosinophilic esophagitis. Gut, 2016;65:524–31. 
Philpott H, Nandurkar S, Royce S, Thien F, Gibson P. A prospective open clinical trial of a 
proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis. 
Aliment Pharmacol Ther, 2016;43:985–93. 
Reed C, Fan C, Koutlas N, Shaheen N, Dellon E. Food elimination diets are effective for long-
term treatment of adults with eosinophilic oesophagitis. Aliment Pharmacol Ther, 
2017;46:836–44. 
Rothenberg M, Wen T, Greenberg A, Alpan O, Enav B, Hirano I, et al. Intravenous anti-IL-13 
mAb QAX576 for the treatment of eosinophilic esophagitis. J Allergy Clin Immunol, 
2014;135:500–07. 
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. 
Spergel J, Rothenberg M, Collins M, Furuta G, Markowitz J, Fuchs III G, et al. Reslizumab in 
children and adolescents with eosinophilic esophagitis: results of a double-blind, 
randomized, placebo-controlled trial. Journal of Allergy and Clinical Immunology, 
2012;129:456–63. 
Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, et al. Anti-interleukin-5 
antibody treatment (mepolizumab) in active eosinophilic oesophagitis: A randomised, 
placebo-controlled, double-blind trial. Gut, 2010;59:21–30. 
Straumann A, Katzka D. Diagnosis and treatment of eosinophilic esophagitis. Gastroenterology, 
2018;154:346–59. 
Syed A, Andrews C, Shaffer E, Urbanski S, Beck P, Storr M. The rising incidence of 
eosinophilic esophagitis is associated with increasing biopsy rates: A population-based 
study. Aliment Pharmacol Ther, 2012;36:950–58. 
Warners M, Oude N, de Wijkerslooth L, Smout A, Bredenoord A. The natural course of 
eosinophilic esophagitis and long-term consequences of undiagnosed disease in a large 
cohort. Am J Gastroenterol, 2018;113:836–44.  


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 1 1 0  of 1 4 0  
C o nfi de nti al  
1 9.
A p pe n dices
1 9. 1   
A p pe n di x 1:  D ys p ha gia S y m pt o m Q uesti o n naire ( Pa per a n d El ectr o nic V ersi o ns) 
1 9. 2  
A p pe n di x 2:  S oli d F o o d Q uesti o n  ( Pa per Versi o n) 
1 9. 3  
A p pe n di x 3: 
 ( Pa per Versi o n) 
1 9. 4  
A p pe n di x 4: 
 ( Pa p er Versi o n) 
1 9. 5  
A p pe n di x 5:  E G/ E o D P R O Q uesti o n naire  ( Pa p er Versi o n) 
1 9. 6  
A p pe n di x 6: 
 ( Pa per V ersi o n) 
1 9. 7  
A p pe n di x 7: 
Baseli ne D iet Assess me nt 
1 9. 8  
A p pe n di x 8:  C o m m o n Ter mi n ol o g y Criteria f or A d vers e E ve nts  ( Versi o n 5. 0) 
1 9. 9  
A p pe n di x 9: 
E G D Hist ol o g y  
1 9. 1 0  A p pe n di x 1 0:  Sa m ps o n’s Criteria of A na p h yla xis  
1 9. 1 1  A p pe n di x 1 1: Baseli ne D S Q a n d Bi wee kl y Mea n  D S Q Calc ulati o n  
1 9. 1 2  A p pe n di x 1 2: O pe n - La b el E xte n de d D osi n g Peri o d ( O pti o nal) 
C CI
C CI
C CI


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19.1 
Appendix 1: Dysphagia Symptom Questionnaire (Paper and Electronic Versions) 


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19.1 
Appendix 1: Dysphagia Symptom Questionnaire cont. 


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19.1 
Appendix 1: Dysphagia Symptom Questionnaire cont. 


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19.1 
Appendix 1: Dysphagia Symptom Questionnaire cont. 


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19.1 
Appendix 1: Dysphagia Symptom Questionnaire cont. 


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19.2 
Appendix 2: Solid Food Question (Paper Version) 


Pr ot oc ol A K 0 0 2 -0 1 4  
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Pr ot oc ol A K 0 0 2 -0 1 4  
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Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 1 1 8  of 1 4 0  
C o nfi de nti al  
C CI


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19.5 
Appendix 5: EG/EoD PRO Questionnaire (Paper Version) 


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19.5 
Appendix 5: EG/EoD PRO Questionnaire cont. 


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19.5 
Appendix 5: EG/EoD PRO Questionnaire cont. 
©2000, the Rome Foundation, Inc. 
For any information on the use of the BSFS, please contact Mapi Research Trust, Lyon, France. Internet: https://eprovide.mapi-trust.org 


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Pr ot oc ol A K 0 0 2 -0 1 4  
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Date : 2 8  Oct 2 0 2 1  
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C o nfi de nti al  
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Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 1 2 4  of 1 4 0  
C o nfi de nti al  
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 1 2 5  of 1 4 0  
C o nfi de nti al  
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
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Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 1 2 6  of 1 4 0  
C o nfi de nti al  
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8  Oct 2 0 2 1  
Alla k os I nc.  
Pa ge 1 2 7  of 1 4 0  
C o nfi de nti al  
C CI
C CI


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19.7 
Appendix 7: 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 the 
Screening Period. 
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 EoE worse?
Yes ☐ No ☐ 
If Yes, what are the 3 specific foods/types of foods that make the effects worse?
Food or Type of Food 
Effect 
4.
Do you avoid eating any specific foods or types of foods due to your EoE?
Yes ☐ No ☐ 
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 EoE?
Yes ☐ No ☐ 
If Yes, please describe:
__________________ 


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19.8 
Appendix 8: Common Terminology Criteria for Adverse Events (Version 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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19.9 
Appendix 9: EGD Histology 
Details for collecting, labeling, and shipping specimens will be provided separately. 
Staining: The performance of the evaluations listed below will require the following stains for 
each biopsy set: 
•
Esophagus: 1) H&E; 2) tryptase; 3) trichrome
•
Stomach: 
1) H. pylori immunostain; 2) H&E; 3) tryptase; 4) trichrome
•
Duodenum: 1) H&E; 2) tryptase; 3) trichrome
Biopsies will be obtained from the following: 
•
Esophagus
−
A set of 2 fragments from the distal esophagus
−
A set of 2 fragments from the mid-proximal esophagus.
−
Up to 2 extra specimens may be collected if there are any additional areas of interest
A count of ≥15 eosinophils per hpf in at least one esophageal site will be considered 
diagnostic of eosinophilic esophagitis (EoE).  
•
Stomach
−
A set of 4 specimens from separate areas of the gastric antrum (2–5 cm proximal to the
pylorus)
−
A set of 4 specimens from separate areas of the gastric corpus (two from the proximal
lesser curvature and two from the greater curvature)
−
Up to 2 extra specimens may be collected if there are any additional areas of interest
A count of ≥30 eosinophils per hpf in at least 5 hpf will be considered diagnostic of 
eosinophilic gastritis (EG). 
•
Duodenum
−
4 fragments of duodenal mucosa from the second and third part of the duodenum.
−
Up to 2 extra specimens may be collected if there are any additional areas of interest
A count of ≥30 eosinophils per hpf in at least 3 hpf will be considered diagnostic of 
eosinophilic duodenitis (EoD). 
Note: Any stored tissue from biopsies of the esophagus, stomach, or duodenum may be used for 
exploratory analysis. 


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19.9 
Appendix 9: EGD Histology cont. 
The following will be reported for esophageal biopsies: 
•
Maximum number of eosinophils per hpf
•
Maximum number of tryptase-positive mast cells per hpf
In addition, the following histopathologic parameters will be graded from 0 (absent) to 
3 (marked or severe): 
•
Eosinophilic microabscesses
•
Eosinophilic degranulation
•
Basal zone hyperplasia
•
Spongiosis
•
Subepithelial tissue present (Y/N)
•
Lamina propria fibrosis (grade only if subepithelial tissue is present)
The following will be reported for gastric biopsies: 
•
Confirmation of absence of H. pylori. A highly sensitive monoclonal immunohistochemical
stain will be used. If negative, then the subject can be included in the study and the
following histopathologic parameters will be graded using the Sydney System from
0 (absent) to 3 (marked or severe) for all except eosinophil counts:
•
Maximum number of eosinophils per hpf
•
Maximum number of tryptase-positive mast cells per hpf
•
Active inflammation
•
Chronic inflammation
•
Intestinal metaplasia
•
Atrophy
•
Reactive gastropathy
The following will be reported for duodenal biopsies: 
•
Maximum number of eosinophils per hpf
•
Maximum number of tryptase-positive mast cells per hpf
•
Duodenal intraepithelial lymphocytosis (with counts per 100 enterocytes when count
is >20)
•
Villous architecture


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19.10 Appendix 10: Sampson’s Criteria of Anaphylaxis 
ANAPHYLAXIS: Sampson’s definition of anaphylaxis (clinical definition) is the acute onset of 
illness (minutes to several hours) which involves SKIN, MUCOSAL TISSUE, or BOTH (e.g., 
generalized hives, pruritus or flushing, swollen lips-tongue uvula) with 1 OR more of the 
following (Sampson, 2006): 
•
RESPIRATORY: Airway compromise (e.g., dyspnea, wheeze, or bronchospasm, stridor,
reduced PEF, hypoxemia)
•
CIRCULATORY: Reduced blood pressure or associated symptoms of end-organ
dysfunction (e.g., hypotonia, syncope)
OR 
2 or MORE of the following that occur rapidly after exposure: 
•
SKIN, MUCOSAL TISSUE: e.g., generalized hives, itch-flush, swollen lips-tongue-uvula
•
RESPIRATORY: Airway compromise (e.g., dyspnea, wheeze, or bronchospasm, stridor
and reduced PEF)
•
CIRCULATORY: Reduced blood pressure or associated symptoms of end-organ
dysfunction (e.g., hypotonia, syncope)
•
GASTROINTESTINAL: Persistent gastrointestinal symptoms (e.g., Crampy abdominal
pain, vomiting, nausea, diarrhea)


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19.11 Appendix 11: Baseline DSQ and Biweekly Mean DSQ Calculation 
Inclusion Criterion #3: Baseline DSQ (biweekly mean DSQ) score of ≥12 from the last 
2 weeks of screening (the 14 days prior to the first dose) per the 
validated algorithm in Appendix 11. 
If the screening period daily questionnaires were all completed electronically, use the Viedoc 
EDC “Screening DSQ – Biweekly Average Scores” CRF to confirm eligibility because the 
baseline DSQ (the biweekly mean DSQ for the 14 days prior to the first dose) is calculated 
automatically per the following validated algorithm. 
To confirm that the subject meets Inclusion Criterion #3, the Study Coordinator must: 
1)
Click the “+” next to the “Screening DSQ – Biweekly Average Scores” CRF on Day 1.
2)
Review “Baseline DSQ” field at the bottom (biweekly mean DSQ over the past 14 days).
3)
Click “Save Changes” each time in order to save the data as of that date.


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19.11 Appendix 11: Baseline DSQ and Biweekly Mean DSQ Calculation cont. 
If using the EDC system’s automated calculation is not possible for the purpose of analyzing the 
biweekly mean DSQ for study endpoints, use the validated scoring algorithm and methods 
shown below. 
The Dysphagia Symptom Questionnaire was validated with the following scoring algorithm: 


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19.12 Appendix 12: Open-Label Extended Dosing Period (Optional) 
19.12.1 Summary of the Open-Label Extended Dosing Period 
Subjects who complete the double-blind, placebo-controlled treatment period (including the Day 
169 study visit) and meet the open-label extended dosing eligibility criteria will be given the 
option to receive 6 doses of AK002 through the Open-Label Extended Dosing Period (OLE).  
On Day 176 (±3 days), eligible subjects participating in the OLE period will begin following the 
OLE Schedule of Events (Table 5) and will no longer follow the Schedule of Events in Table 1. 
The Extended Dosing Period is summarized as follows:  
•
The Investigator will evaluate whether the subject is eligible for OLE. If eligible, the
subject will be given the option to participate in the OLE period and receive 6 doses of
open-label AK002.
•
On Day 176 (±3 days), eligible subjects who choose to participate in the OLE period will
begin following the OLE Schedule of Events (Table 5).
•
12–24 hours prior to the first open-label AK002 infusion only, subjects will self-administer
oral prednisone premedication (40 mg if body weight is <40 kg, 60 mg if body weight is
≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg).
•
OLE subjects will receive 6 doses of open-label AK002 administered on Days 176 (±3),
204 (±3), 232 (±3), 260 (±3), 288 (±3), and 316 (±3). The first open-label AK002 infusion
will be given at a dose of 1 mg/kg. For subsequent open-label AK002 infusions on
Days 204 (±3), 232 (±3), 260 (±3), 288 (±3), and 316 (±3), each infusion may be given at a
dose of either 1 mg/kg or 3 mg/kg at the discretion of the Investigator.
•
Subjects will remain at the site for at least 1 hour of observation after each dose. In the
event of an IRR, the subject may require prolonged observation (>1 hour or until the
symptoms resolve), as per Investigator discretion.
•
Subjects will be followed for approximately 8 weeks after the last dose. Follow-up visits
will occur on Day 344 (±7) and Day 372 (±7).
•
If absolute lymphocyte and/or eosinophil counts have not recovered by the OLE Day 372
visit, subjects will return approximately every 28 days for extended follow-up until counts
have recovered.


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19.12.2 OLE Objective 
The objective of the OLE period is to evaluate long-term safety and tolerability of up to 6 doses 
of open-label AK002 in subjects with active EoE. The Medical Monitor will review OLE period 
data relating to safety and tolerability throughout the course of open-label extended dosing. 
19.12.3 OLE Eligibility Criteria 
Following completion of the randomized, double-blind, placebo-controlled treatment period 
(including the Day 169 visit), eligible subjects will have the option to receive 6 doses of 
open-label AK002 through participation in the OLE period.  
Subjects who are not eligible for OLE, or who choose not to participate in the OLE period, will 
remain on study and continue to follow the Schedule of Events (Table 1). 
19.12.3.1 OLE Inclusion Criteria 
Subjects are eligible to participate in the OLE period if all the following criteria are met: 
1)
Subject completed the randomized, double-blind, placebo-controlled treatment period and
the Day 169 visit.
2)
Subject is willing and able to comply with the OLE period Schedule of Events (Table 5),
including receiving the first open-label AK002 infusion at the Day 176 (±3 days) visit.
3)
Subject demonstrates continued eligibility per applicable inclusion criteria (Section 7.3) and
exclusion criteria (Section 7.4) of the protocol. “Screening” in Section 7 refers only to the
screening period completed prior to enrollment in the double-blind treatment period of the
study and is not applicable to the OLE period.
19.12.3.2 OLE Exclusion Criteria 
Subjects are not permitted to participate in the OLE period if any of the following criteria are 
met: 
1)
Previous administration of the study drug (AK002 or placebo) was poorly tolerated by the
subject, in the opinion of the Investigator.
2)
Any other reason that, in the opinion of the Investigator or Medical Monitor, makes the
subject unsuitable for participation in the OLE period.
19.12.4 OLE Treatment 
Formulation, storage, preparation, and administration of the open-label AK002 drug product for 
OLE will be consistent with Sections 9.1, 9.3–9.8, and the AK002-014 Pharmacy Manual. 


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 137 of 140 
Confidential 
Twelve to 24 hours prior to the first open-label AK002 infusion only, all subjects will 
self-administer oral prednisone premedication at a dose of 40 mg if body weight is <40 kg, 
60 mg if body weight is ≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg. This dose of 
prednisone premedication should be recorded in the Concomitant Medications CRF of both the 
AK002-014 treatment period database and the AK002-014 OLE period database. 
The first OLE infusion of AK002 will be administered at a dose of 1 mg/kg over ≥4 hours on 
Day 176 (±3 days). At the discretion of the Investigator, either the 1 mg/kg or the 3 mg/kg dose 
may be administered for each subsequent infusion on Days 204 (±3), 232 (±3), 260 (±3), 288 
(±3), and 316 (±3). Depending on the subject’s tolerance per the Infusion Rate Schedules in the 
AK002-014 Pharmacy Manual, the second infusion can be given over ≥3 hours and the third, 
fourth, fifth, and sixth infusions can be given over ≥2 hours. If the infusion is slowed or 
interrupted, the infusion must be completed within 8 hours of preparation (prior to expiry). 
The subject will be observed for at least 1 hour (or greater, as per Investigator discretion) after 
the end of all infusions. In the event of an IRR, the subject may require prolonged observation 
(>1 hour or until the symptoms resolve), as per Investigator discretion. Subjects will also be 
instructed to immediately contact the study doctor if any reactions occur after discharge. 
19.12.5 OLE Procedures and Guidelines 
Apart from differences in the Schedule of Events beginning at Day 176 (±3 days), the OLE 
period of the study will be conducted in accordance with the protocol. This includes prohibited 
medications, dietary and lifestyle restrictions, AK002 preparation and administration, study 
assessment and procedure guidelines, AE reporting, withdrawal criteria and stopping rules, data 
collection and management, and ethical and regulatory requirements. 
The Investigator will evaluate whether the subject is eligible for the OLE period. On Day 176 
(±3 days), eligible subjects that choose to participate in the OLE period will begin following the 
OLE Schedule of Events (Table 5) and will receive the first open-label AK002 infusion.  


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8 Oct  2 0 2 1  
Alla k os I nc.  
Pa ge 1 3 8  of 1 4 0  
C o nfi de nti al  
T a ble 5  
A K 0 0 2- 0 1 4 O pe n- L a bel E xte n de d D osi n g Peri o d Sc he d ule of E ve nts  
Descri pti o n  
Scree ni n g  
O pe n -L a bel E xte n de d D osi n g ( 2 4 wee ks) 
O L E F oll o w -U p ( ≥8 wee ks)2 6 
N o Visit 2 
O L E D ose 1  
D a y 1 7 6  
[ O L E D a y 1] 
( ± 3 d a ys)2 7 
O L E D ose 2  
D a y 2 0 4  
[ O L E D a y 29]  
( ± 3 d a ys)2 7 
O L E D ose 3  
D a y 2 3 2  
[ O L E D a y 57]  
( ± 3 d a ys)2 7 
O L E D ose 4  
D a y 2 6 0  
[ O L E D a y 85]  
( ± 3 d a ys)2 7 
O L E D ose 5  
D a y 2 8 8  
[ O L E D a y 1 13]  
( ± 3 da ys)2 7 
O L E D ose 6  
D a y 3 1 6  
[ O L E D a y 1 41]  
( ± 3 da ys)2 7 
D a y 3 4 4  
[ O L E D a y 1 69]  
( ± 3 da ys) 2 7 
D a y 3 7 2  
[ O L E D a y 1 9 7]  
( ± 7 da ys) or E T 2 5 
E val uate Eli gi bilit y f or O L E Peri o d 2 
X 2 
X 2 
D S Q P R O 3 
D aily t hr o u g h E n d of St u dy ( or E T) ------------------------------------------------------------------------------------------------> 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X  
Baseli ne Diet C o m plia nce 5 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
Wei g ht a n d Vital Si g ns
6, 7 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X  
X  
T otal Ser u m I g E 8, 9 
X 1 
X 
C B C w it h Differe ntial8, 1 0 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
C he mistr y 8, 1 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
P har mac o ki netics 8, 1 2 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
A nti -dr u g A nti b o dies 8, 1 3 
X 1 
X 1 3 
X 1 3 
X 1 3 
X 1 3 
X 1 3 
X 
E x pl orat or y A nal ysis 8, 1 4 
X 1 
X 
E x pl orat or y Safet y 8, 1 5 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
Uri nal ysis 8, 1 6 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
Uri ne Pre g na nc y Test 8, 1 7 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
Pre me dicati o n: Pre d nis o ne 1 8 
X 1 8 
A K 0 0 2 A d mi nistrati o n 1 9 
X 
X 
X 
X 
X 
X 
P ost -D ose O bser vati o n Peri o d 2 0 
X 
X 
X 
X 
X 
X 
S y m pt o m -Directe d P h ysical E xa m 2 1 
X  
X  
X  
X  
X  
X  
X  
X  
E G D wit h Bi o ps y C ollecti o n 2 2 
X 
X ( E T  o nl y)2 5 
E R E F S Sc ori n g d uri n g E G D 2 3 
X  
X ( E T o nl y) 2 5 
C o nc o mita nt Me dicati o ns  
X 
X 
X 
X 
X 
X 
X 
X 
A d verse E ve nts 2 4 
X  
X  
X  
X  
X  
X  
X  
X  
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
A me n d me nt 6 
Date : 2 8 Oct  2 0 2 1  
Alla k os I nc.  
Pa ge 1 3 9  of 1 4 0  
C o nfi de nti al  
A D A:  A nti -dr u g A nti b o d y  
D S Q:  D ys p ha gia S y m pt o m Q uesti o n naire  
P K:  P har mac o ki netics  
C B C:  C o m plete Bl o o d C o u nt  
E T:  
Earl y Ter mi nati o n  
T a ble 5 N otes  
1)
Refer t o assess me nt f o ot n ote f or s pecific ti mi n g (e. g., pre d ose, d uri n g i nf usi o n, p ost d ose).
2)
T he I n vesti gat or will e val uate w het her t he s u bject is eli gi ble f or t he O L E peri o d  per Secti o n 1 9. 1 2. 3 . O n Da y 1 7 6 ( ± 3 da ys), eli gi ble s u bjects t hat c h o ose t o partici pate i n t he
O L E peri o d  will be gi n f oll o wi n g t he O L E Sc he d ule of E ve nts a n d will recei ve t he first o pe n -la bel A K 0 0 2 i nf usi o n.
3)
S u bjects s h o ul d c o m plete t he D S Q dail y after t he last meal of t he da y. If Q uesti o n 1 is a ns were d “ N o,” t he s u bject s h o ul d a ns wer t he S oli d  F o o d Q uesti o n ( A p pe n di x 2 ) after
t he D S Q is c o m plete d a n d s u b mitte d. T he site is res p o nsi ble f or m o nit ori n g c o m plia nce a n d disc ussi n g c o m plia nce d uri n g st u d y visits.
4)
 s h o ul d be t he first assess me nt c o m plete d b y t he s u bject at t he be gi n ni n g of t he st u d y visit pri or t o ot her assess me nts.
5)
Per I ncl usi o n Criteri o n  # 7 , s u bjects s h o ul d mai ntai n t he baseli ne diet c o nsiste ntl y t hr o u g h o ut t he st u d y. Diet c o m plia nce will be disc usse d d uri n g st u d y visits a n d a n y
varia nce will be d oc u me nte d.
6)
Wei g ht will be meas ure d pre d ose o n Da ys 1 7 6, 2 0 4, 2 3 2, 2 6 0, 2 8 8, a n d 3 1 6, a n d Da ys 3 4 4 a n d 3 7 2 ( or E T).
7)
Vital si g ns will be meas ure d at all O L E visits. O n d osi n g da ys ( D a ys 1 7 6, 2 0 4, 2 3 2, 2 6 0, 2 8 8, a n d 3 1 6), vital si g ns will be meas ure d pre d ose, 1 5 mi n utes ( ± 5 mi n utes) after
i nf usi o n start, i m me diatel y p ost d ose ( wit hi n 5 mi n utes after i nf usi o n e n d), a n d 1 h o ur ( ± 5 mi n utes) p ost d ose. S u bject s h o ul d be at rest f or ≥5 mi n ute s bef ore vital si g ns
(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) are meas ure d.
8)
Please see t he Ce ntral La b orat or y Ma n ual f or c ollecti o n, pr ocessi n g, a n d s hi p me nt i nstr ucti o ns. Sa m ples s h o ul d be s hi p pe d o n t he same da y as c ollecti o n.
9)
Bl o o d f or t otal ser u m I g E will be o btai ne d pre d ose o n Da y 3 1 6 a n d a gai n o n Da y 3 7 2 ( or E T).
1 0)
Bl o o d f or C B C wit h differe ntial will be o btai ne d at all O L E peri o d  st u d y visits. O n Da ys 1 7 6, 2 0 4, 2 3 2, 2 6 0, 2 8 8, a n d 3 1 6, bl o o d will b e dra w n t wice ( pre d ose a n d 1 -h o ur
p ost d ose).
1 1)
Bl o o d f or c he mistr y will be o btai ne d at all O L E peri o d  st u d y visits. O n Da ys 1 7 6, 2 0 4, 2 3 2, 2 6 0, 2 8 8, a n d 3 1 6, bl o o d f or c he mistr y will be dra w n pre d ose.
1 2)
Bl o o d f or P K will be o btai ne d at all O L E peri o d  st u d y visits. O n Da ys 1 7 6, 2 0 4, 2 3 2, 2 6 0, 2 8 8, a n d 3 1 6, bl o o d f or P K will be dra w n pre d ose.
1 3)
Bl o o d f or A D A will be o btai ne d pre d ose o n Da y 1 7 6 a n d o n Da y 3 7 2 ( or E T). F or Da ys 2 0 4, 2 3 2, 2 6 0, 2 8 8, a n d 3 1 6, bl o o d f or A D A  will be o btai ne d o nl y if a s us pecte d
i m m u n o ge nicit y-relate d A E  occ urs.
1 4)
Bl o o d f or e x pl orat or y a nal ysis will be o btai ne d pre d ose o n Da y 3 1 6 a n d o n Da y 3 7 2 ( or E T).
1 5)
Bl o o d f or e x pl orat or y safet y a nal yses will o nl y be o btai ne d wit hi n 1 – 2 h o urs of s y m pt o m o nset if a n I R R res ults i n i nf usi o n i nterr u pti o n or cessati o n.
1 6)
Uri ne f or uri nal ysis will be o btai ne d pre d ose o n Da y 1 7 6, as nee de d (if warra nte d i n t he o pi ni o n of t he I n vesti gat or or S u bi n vesti gat or), a n d o n Da y 3 7 2.
1 7)
F or fe males of c hil d beari n g p ote ntial, uri ne will be c ollecte d, teste d, a n d pre g na nc y res ult c o nfir me d pre d ose o n Da ys 1 7 6, 2 0 4, 2 3 2, 2 6 0, 2 8 8, a n d 3 1 6.
C CI


Protocol AK002-014 
Amendment 6 
Date: 28 Oct 2021 
Allakos Inc. 
Page 140 of 140 
Confidential 
Table 5 Notes cont. 
18)
The day before the first open-label AK002 dose (12–24 hours prior to the infusion start time), subjects will self-administer oral prednisone premedication at a dose of 40 mg
if body weight is <40 kg, 60 mg if body weight is ≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg. This dose of prednisone premedication should be recorded in the
Concomitant Medications CRF of both the AK002-014 treatment period database and the AK002-014 OLE period database.
19)
Open-label AK002 will be administered as a single peripheral IV infusion over ≥4 hours on Day 176, over ≥3 hours on Day 204, and over ≥2 hours on Days 232, 260, 288,
and 316. Refer to the Pharmacy Manual for detailed administration and infusion rate schedule instructions.
20)
Subjects will remain under observation at the site for at least 1 hour after the end of each infusion. In the event of an IRR, the subject may require prolonged observation
(>1 hour or until the symptoms resolve), as per Investigator discretion. Subjects will also be instructed to immediately contact the study doctor if any reactions occur after
discharge.
21)
If a new or worsening symptom (or clinically significant finding) is observed or reported, the Investigator or designee will determine whether a symptom-directed physical
examination is warranted. Symptom-directed physical examinations will be performed if warranted (per the Investigator or designee judgment) and may be performed at any
time or multiple times during a visit (predose, during infusion, and/or postdose).
22)
An EGD with biopsy collection will be performed on Day 344 (±3 days). EGD biopsies will be collected, processed, and shipped in accordance with Appendix 9, the central
laboratory manual, and the histology manual.
23)
During the Day 344 EGD, severity will be evaluated using the EoE Reference Score for Endoscopic Abnormalities per the AK002-014 Histology Manual.
24)
All AE, including AESI and SAE, will be captured through the entire OLE period until Day 372 (or ET). Adverse events will be assessed and recorded in the CRF of the
AK002-014 OLE period database beginning from the start of the first open-label infusion during the Day 176 visit.
25)
The ET visit should be conducted 28 (±3) days after the last dose of open-label AK002 or prior to this, if necessary, to ensure compliance with the visit. If ET occurs after the
Day 204 study visit and before the Day 344 study visit, then an EGD with biopsy collection must be done 28 (±3) days after the last dose of open-label AK002. If a subject
discontinues the study >28 days after the last dose of study drug, the ET visit should be conducted as soon as possible.
26)
If absolute lymphocyte and/or eosinophil counts do not recover (to normal range or baseline levels) by Day 372 (or ET), extended follow-up visits are required every 28 days
(±3 days) thereafter to monitor blood counts until they recover. Extended follow-up visits consist of blood collection for CBC with differential and collection of AESI and
SAE.
27)
Sites should strive to conduct visits within a ±3 day window, but visits conducted within ±7 days are acceptable and are not considered deviations. Visits conducted ±4-7 days
from the target visit date should be minimized as much as possible. Any visit conducted outside of the ±3 day window should receive prior written approval from Allakos.

SAP_001.pdf: 
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study 
to Evaluate the Efficacy and Safety of AK002 in Adult and Adolescent Subjects 
with Active Eosinophilic Esophagitis  
NCT Number: NCT04322708
Document Date: 10 Nov 2021


Page 1 of 66 
Statistical Analysis Plan for Protocol AK002-014 
Protocol Title 
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of AK002 in Adult and 
Adolescent Subjects with Active Eosinophilic Esophagitis  
Protocol Number AK002-014 
Protocol Version Amendment 6 
Protocol Date 
Amendment 6 
28 October 2021 
Amendment 5 
07 May 2021 
Amendment 4 
20 August 2020 
Amendment 3 
08 July 2020 
Amendment 2 
07 May 2020 
Amendment 1 
13 January 2020 
Original 
16 October 2019 
Study Drug 
AK002 
Study Phase 
2/3 
IND Number 
143997 
Sponsor 
Allakos Inc., 975 Island Drive, Suite 201, Redwood City, CA 94065 USA 
SAP Version 
1 
SAP Date 
10 November 2021 
SIGN


Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 2 of 66 
Confidential 
Signature Page 
 
Prepared by: 
 
 
 PhD 
Director, Biometrics 
Allakos Inc. 
 
Date 
 
Reviewed and 
Approved by: 
 
 
 PhD 
 Biometrics 
Allakos Inc. 
Date 
 
 
 
 MD, MBA 
 
Allakos Inc. 
Date 


	

PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 3 of 66 
Confidential 
Table of Contents 
Statistical Analysis Plan for Protocol AK002-014.......................................................................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 ..........................................................12 
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 
Schedule of Events ....................................................................................................16 
3.3 
Study Treatment ........................................................................................................21 
3.3.1 
Treatment, Dose, and Mode of Administration ............................................21 
3.3.2 
Duration of Study .........................................................................................21 
3.3.3 
Methods of Assigning Subjects to Treatment Group ...................................21 
3.4 
Blinding .....................................................................................................................21 
3.5 
Hypotheses ................................................................................................................22 
3.6 
Determination of Sample Size ...................................................................................22 
4. 
Definitions ............................................................................................................................23 
4.1 
Terminology and Definitions ....................................................................................23 


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 4 of 66 
Confidential 
4.2 
Target of Estimation ..................................................................................................24 
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 .....................................25 
4.2.3 
Treatment .....................................................................................................25 
4.2.4 
Intercurrent Events .......................................................................................25 
4.2.5 
Strategy for Handling Intercurrent Events ...................................................25 
4.2.6 
Summary Measure of Estimand ...................................................................26 
5. 
Statistical Methods ..............................................................................................................26 
5.1 
General Methodology ................................................................................................26 
5.2 
Visit Window and Unscheduled Assessments ..........................................................27 
5.3 
Adjustment for Covariates .........................................................................................30 
5.4 
Handling of Dropouts, Missing Data, and Data Discrepancies .................................30 
5.4.1 
Missing Tissue Eosinophil Count at Week 24 .............................................30 
5.4.2 
Missing Daily PRO Scores at Weeks 23–24 ................................................30 
5.4.3 
Missing or Partial Dates of Adverse Events or Concomitant Medications ..31 
5.5 
Interim Analysis ........................................................................................................31 
5.6 
Timing of Final Analyses ..........................................................................................31 
5.7 
Multicenter Study ......................................................................................................32 
5.8 
Multiple Comparisons/Multiplicity Adjustment .......................................................33 
5.9 
Examination of Subgroups ........................................................................................33 
6. 
Statistical Analysis ...............................................................................................................34 
6.1 
Analysis Populations .................................................................................................34 
6.1.1 
Safety Population .........................................................................................34 
6.1.2 
Intent-to-Treat Population ............................................................................34 
6.1.3 
Modified Intent-to-Treat Population ............................................................34 


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 5 of 66 
Confidential 
6.1.4 
Per Protocol Analysis population .................................................................34 
6.1.5 
Primary Analysis population ........................................................................34 
6.2 
Disposition of Subjects ..............................................................................................34 
6.3 
Protocol Deviations ...................................................................................................35 
6.4 
Demographics and Baseline Subject Characteristics ................................................35 
6.5 
Baseline Disease Characteristics ...............................................................................36 
6.6 
Medical History .........................................................................................................36 
6.7 
Electrocardiogram .....................................................................................................36 
6.8 
Pregnancy Test ..........................................................................................................36 
6.9 
Baseline Diet .............................................................................................................36 
6.10 
Treatments .................................................................................................................36 
6.10.1 Treatment Compliance and Extent of Exposure ..........................................36 
6.10.2 Prior, Concomitant, and Newly Initiated Medications .................................37 
6.11 
Analysis of Primary Efficacy Endpoints ...................................................................37 
6.11.1 Analysis of the First Co-Primary Endpoint ..................................................37 
6.11.2 Sensitivity Analysis of the First Co-Primary Endpoint ................................38 
6.11.3 Subgroup Analysis of the First Co-Primary Endpoint .................................38 
6.11.4 Analysis of the Second Co-Primary Endpoint .............................................38 
6.11.5 Sensitivity Analyses of the Second Co-Primary Endpoint ...........................39 
6.11.6 Supplementary Analyses ..............................................................................40 
6.12 
Analysis of Secondary Efficacy Endpoints ...............................................................40 
6.12.1 Percent Change in Tissue Eosinophil Count ................................................40 
6.12.2 Proportion of Subjects Achieving Peak Esophageal Intraepithelial 
Eosinophil Count of ≤1 and <15 Eosinophils/hpf at Week 24 .....................40 
6.12.3 Proportion of Treatment Responders ...........................................................41 
6.12.4 Proportion of Subjects with >50% Improvement in DSQ from Baseline 
to Weeks 23–24 ............................................................................................41 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 6 of 6 6  
C o nfi de nti al  
6. 1 2. 5  Perce nt C ha n ge i n D S Q fr o m Baseli ne t o Wee ks 2 3 – 2 4 ............................. 4 1  
6. 1 2. 6  C ha n ge i n Bi wee kl y Mea n D S Q O ver Ti me ................................................ 4 1  
6. 1 2. 7  C ha n ge i n E o E E n d osc o pic Refere nce Sc ore  ............................................... 4 1 
6. 1 3  
A nal ysis of E x pl orat or y E n d p oi nts ........................................................................... 4 2  
6. 1 3. 1  C ha n ge i n 
 ......................................... 4 2 
6. 1 3. 2  C ha n ge i n  
 ........................................................................................... 4 3  
6. 1 3. 3  C ha n ge i n 
 ......................................................................... 4 3 
 
6. 1 4  
A nal ysis of P har mac o ki n etic E n d p oi nt ..................................................................... 4 3  
6. 1 5  
Safet y A nal yses  ......................................................................................................... 4 3 
6. 1 5. 1  A d verse E v e nts  ............................................................................................. 4 3 
6. 1 5. 2  La b orat or y T est ............................................................................................ 4 5  
6. 1 5. 3  Vital Si g ns, Hei g ht a n d Wei g ht, a n d Ot her Safet y Meas ures ...................... 4 5  
6. 1 5. 4  Electr ocar di o gra ms  ....................................................................................... 4 5 
6. 1 5. 5  P h ysical E xa mi nati o n  ................................................................................... 4 5 
6. 1 5. 6  A nal ysis of A nti- Dr u g A nti b o d y .................................................................. 4 5  
7.  
V ali d ati o n ............................................................................................................................. 4 6  
8.  
Refere nces  ............................................................................................................................ 4 7 
9.  
A p pe n dices  ........................................................................................................................... 4 8 
9. 1  
A p pe n di x 1: D ys p ha gia S y m pt o m Q uesti o n naire, 
 
, a n d E o E E n d osc o pic Refere n ce Sc ore .......................... 4 9 
9. 2  
A p pe n di x 2: I nterc urre nt E ve nts  ............................................................................... 5 7 
9. 3  
A p pe n di x 3: List of Ta bles, Listi n gs, a n d Fi g ures .................................................... 6 0  
9. 4  
A p pe n di x 4 E xa m ple S A S C o des .............................................................................. 6 6  
 
 
 
 
C CI
C CI
C CI
C CI
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Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 7 of 6 6  
C o nfi de nti al  
List of I n-Te xt T a bles  
Ta ble  1 
A K 0 0 2 - 0 1 4 Sc he d ule of E ve nts............................................................................. 1 7 
Ta ble 2  
Ter mi n ol o g y a n d Defi niti o ns ................................................................................. 2 3  
Ta ble 3  
A nal ysis Wi n d o w R ules f or  
 ........................................................................ 2 8  
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 8  
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 9  
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 9  
Ta ble  7 
H y p ot hesis Testi n g Or der Hierarc h y ..................................................................... 3 3  
 
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 8 of 6 6  
C o nfi de nti al  
List of A b bre vi ati o ns 
A D A  
A nti -dr u g a nti b o d y(ies)  
A Da M  
A nal ysis Data M o del  
A E  
A d verse e ve nt (s) 
A N C O V A  
A nal ysis of c o varia nce 
A T C  
A nat o mical T hera pe utic C he mical Classificati o n S yste m  
B L O Q  
Bel o w li mit of q ua ntitati o n  
B MI  
B o d y mass i n de x  
B Z H  
Basal z o ne h y per plasia  
C B C  
C o m plete bl o o d c o u nt  
C DI S C  
Cli nical Data I nterc ha n ge Sta n dar ds C o ns orti u m  
CI  
C o nfi de nce i nter val  
C M H   
Coc hra n -Ma ntel -Hae nszel  
C R F  
Case Re p ort F or m  
C R O  
C o ntract Researc h Or ga nizati o n  
C S R  
Cli nical St u d y Re p ort  
C V  
C oefficie nt of variati o n  
D E C  
D ys kerat otic e pit helial cells  
DI S  
Dilate d i ntercell ular s paces  
D M  
Data ma na ge me nt  
D S Q  
D ys p ha gia S y m pt o m  Q uesti o n naire  
E A  
E osi n o p hil a bscess  
E C G  
Electr ocar di o gra m  
e C D F  
e m pirical C u m ulati ve Distri b uti o n F u ncti o n  
e C R F  
electr o nic Case Re p ort F or m  
E D C  
Electr o nic Data Ca pt ure (s yste m)  
E G  
E osi n o p hilic gastritis  
E G D  
Es o p ha g o gastr o d u o de n osc o p y  
EI  
E osi n o p hilic i nfla m mati o n  
E o E  
E osi n o p hilic es o p ha gitis  
E o D  
E osi n o p hilic d u o de nitis  
 
  
E R E F S  
E osi n o p hilic Es o p ha gitis E n d osc o pic Refere nce Sc ore  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 9 of 6 6  
C o nfi de nti al  
E T  
Earl y Ter mi nati o n  
F D A 
F o o d a n d Dr u g A d mi nistrati o n  
F S H  
F ollicle -Sti m ulati n g H or m o ne  
GI  
Gastr oi ntesti nal  
h C G  
h u ma n c h ori o nic g o na d otr o pi n  
h pf  
Hi g h p o wer fiel d  
I C E 
I nterc urre nt e ve nt(s) 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I C F 
I nf or me d C o nse nt F or m 
I R R 
I nf usi o n-relate d reacti o n(s) 
I R T 
I nteracti ve Res p o nse Tec h n ol o g y 
I T T 
I nte nt-t o-Treat ( p o p ulati o n)  
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 P F  
La mi na pr o pria fi br osis  
L S M  
Least s q uares mea n(s)  
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  
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  
O L E  
O pe n -la bel e xte nsi o n ( peri o d) 
 
 
 
 
P E C  
Pea k e osi n o p hil c o u nt  
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 T  
Preferre d ter m  
P R O  
Patie nt -re p orte d o utc o me ( q uesti o n naire) 
p- val ue  
Pr o ba bilit y val ue  
S A E  
Seri o us a d verse e ve nt (s) 
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 0  of 6 6  
C o nfi de nti al  
S A P  
Statistical A nal ysis Pla n  
S E A  
S urface e pit helial alterati o n  
S D  
Sta n dar d de viati o n  
S D T M  
St u d y Data Ta b ulati o n M o del  
S E  
Sta n dar d err or (s) 
 
 
S L  
S urface la yeri n g  
S O C  
S yste m or ga n class  
T E A E  
Treat me nt -e mer ge nt a d verse e ve nt (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 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  
T N F  
T u m or necr osis fact or  
T S S  
T otal S y m p t o m Sc ore 
U L N  
U p per li mit of n or mal  
W H O  
W orl d Healt h Or ga nizati o n  
W H O D D  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
 
C CI


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 11 of 66 
Confidential 
 
Revision History 
Version Date 
Version Number 
Description 
10 Nov 2021 
1 
Initial document 
 


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 12 of 66 
Confidential 
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 adult and adolescent subjects with active 
eosinophilic esophagitis (EoE) 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 pharmacokinetics (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 AK002-014 Amendment 6, dated 28 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 adult and adolescent subjects when compared to placebo. 
Efficacy endpoints will be co-primary: 
1) 
The proportion of subjects who achieve a peak esophageal intraepithelial count of 
≤6 eosinophils/hpf at Week 24. 
2) 
Mean change in Dysphagia Symptom Questionnaire (DSQ) score from Baseline to 
Weeks 23–24. 
2.2 
Secondary Objectives – Secondary Endpoints 
The secondary objectives are to evaluate the clinical benefit of AK002 in adult and adolescent 
subjects with active EoE when compared to placebo as measured by: 
1) 
Percent change in peak esophageal intraepithelial eosinophil count at Week 24. 
2) 
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of 
≤1 eosinophil/hpf at Week 24. 
3) 
Proportion of subjects achieving peak esophageal intraepithelial eosinophil count of 
<15 eosinophils/hpf at Week 24. 
4) 
Proportion of treatment responders when a responder is a subject achieving >30% reduction 
in symptoms (DSQ) at Weeks 23–24 and achieving a peak intraepithelial eosinophilic count 
of ≤6 eosinophils/hpf at Week 24. 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 3  of 6 6  
C o nfi de nti al  
5)  
Pr o p orti o n of s u bjects wit h  > 5 0 % re d u cti o n i n D S Q sc ore fr o m Baseli ne t o Wee ks  2 3 – 2 4. 
6) 
Perce nt c h a n ge i n D S Q s c ore fr o m Baseli ne t o Wee ks 2 3 – 2 4. 
7)  
C ha n ge i n bi wee kl y mea n D S Q o ver ti me. 
8)  
C ha n ge i n E o E E n d osc o pic Refer e nce Sc ore ( E R E F S) fr o m Baseli ne t o Wee k 2 4 . 
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 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 para meters:  
1)  
C ha n ge i n c o m p o ne nts ( Secti o n 6. 1 3. 1) of 
 
fr o m Baseli ne t o Wee k 2 4. 
2)  
C ha n g e i n 
 
 fr o m Bas eli ne t o Wee k 2 4. 
3) 
C ha n ge i n 
 fr o m Baseli ne t o Wee k 2 4. 
2. 4  
S afet y O bjecti v es  – S afet y E n d p oi nts  
T he safet y o bjecti ve of t h e 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:  
•  
Treat me nt e mer ge nt a d v erse e ve nts  ( T E A E) i ncl u di n g se verit y, relati o ns hi p t o st u d y 
treat me nt, acti o n ta k e n, a n d o utc o me, seri o us a d verse e ve nts ( S A E ), a n d a d verse e v e nts 
(A E ) lea di ng t o st u d y dr u g wit h dra wal 
•  
A nti - dr u g ( A K 0 0 2) a nti b o d y (A D A )  
•  
Bl o o d c he mistr y  
•  
He mat ol o g y  
•  
Uri nal ysis  
•  
P h ysical e xa mi nati o n  
•  
C ha n ges i n vital si g ns  
•  
C ha n ges i n c o nc o mita nt me dicati o n use d ue t o A E   
C CI
C CI
C CI


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 14 of 66 
Confidential 
3. 
Study Design 
3.1 
General Description 
This is a Phase 2/3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the safety, tolerability, and clinical benefit of AK002 in adult and adolescent subjects with active 
EoE. Subjects enrolled in the study will receive 6 infusions of placebo or AK002 administered 
every 4 weeks and will be followed for 8 weeks after the last dose. 
Subjects who complete the double-blind, placebo-controlled treatment and the Day 169 visit may 
have the option to receive 6 doses of open-label AK002 through participation in the optional 
Open-Label Extension (OLE) Period of the study and will be followed for 8 weeks after the last 
dose. 
Subjects will be consented and then screened for 14 to 60 days. During the screening period, a 
baseline, stable regimen of proton pump inhibitors (PPI) and/or dietary intake will be 
established, if needed, and baseline disease activity data will be collected. Swallowed topical 
corticosteroids and systemic corticosteroids will not be allowed. Subjects who meet eligibility 
criteria can be enrolled in the study. Subjects who do not meet all eligibility criteria at screening, 
or who qualify at screening but are not enrolled, may be assigned a new subject identification 
number and rescreened once. Subjects rescreened within 30 days of signing the initial informed 
consent form (ICF) will not need to reconsent if no changes have been made to the ICF. 
Prior to the first dose of study drug (12–24 hours prior to the infusion), subjects will be 
premedicated with oral prednisone (40 mg if body weight is <40 kg, 60 mg if body weight is 
≥40 kg and <60 kg, or 80 mg if body weight is ≥60 kg). Subjects will self-administer oral 
prednisone 12–24 hours prior to the start of the first infusion only.  
Eligible subjects will receive the first dose of placebo or AK002 (1 mg/kg) on Day 1 and will 
remain confined to the clinic for at least 1 hour of observation (or greater, as per Investigator 
discretion) following the end of the infusion. On Day 29, subjects will receive a second dose of 
placebo or AK002 (1 mg/kg or 3 mg/kg) and will remain confined to the clinic for at least 1 hour 
of observation (or greater, as per Investigator discretion) following the end of the infusion. If the 
study drug is well tolerated (no stopping rules met), subjects will continue to receive doses of 
placebo, 1 mg/kg AK002, or 3 mg/kg AK002 on Days 57, 85, 113, and 141 for a total of 6 doses. 
Subjects will remain at the site for at least 1 hour of observation (or longer, as per Investigator 
discretion) after each dose. In the event of an infusion-related reaction (IRR), the subject may 
require prolonged observation (>1 hour or until the symptoms resolve), as per the Investigator’s 
discretion. Subjects will also be instructed to immediately contact the study doctor if any 
reactions occur after discharge. 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 5  of 6 6  
C o nfi de nti al  
D uri n g t he Treat me nt Peri o d, s u bjects will ret ur n t o t he cli nic f or st u d y visits as descri be d i n t he 
Sc he d ule of E ve nts ( T a bl e  1). After c o m pleti o n of t he Da y 1 6 9 visit, t he I n v esti gat or will 
e val uate w h et her t he s u bj ect is eli gi ble f or t he O L E Peri o d. S u bjects w h o s uccessf ull y c o m plete 
t he d o u ble- bli n d treat me nt peri o d  (i ncl u di n g t he Da y 1 6 9 visit) will ha ve t he o pti o n t o partici pate 
i n t he O L E Peri o d, pr o vi de d all eli gi bilit y criteria f or t he O L E Peri o d are s atisfie d. 
S u bjects w h o are n ot eli gi ble f or ( or w h o c h o ose n ot t o partici pate i n) t he O L E Peri o d will 
c o m plete t he F oll o w- U p Peri o d, i ncl u di n g t he Da y 1 6 9 ( ± 7) visit ( 4 wee ks after t he l ast d ose) 
a n d t he Da y 1 9 7 ( ± 7) visit ( 8 wee ks aft er t he last d ose) per t he S c he d ule of E ve nts ( Ta ble  1). 
Eli gi ble s u bjects w h o c h o ose t o partici pate i n t he O L E Peri o d will be gi n f oll o wi n g t he O L E 
Sc he d ule of E ve nts a n d will recei ve t he first d ose of o pe n-la b el A K 0 0 2 a p pr o xi matel y 1 wee k 
after D a y 1 6 9 ( o n D a y 1 7 6 ± 3 da ys). 
If a bs ol ute l y m p h oc yte a n d/ or e osi n o p hil c o u nts ha ve n ot rec o vere d (t o n or mal ra n ge or b aseli ne 
le vels) b y t he Da y 1 9 7 visit ( or t he Da y 3 7 2 visit f or s u bjects partici pati n g i n t he O L E Peri o d), 
e xte n de d f oll o w- u p visits are r e q uire d a p pr o xi mat el y e ver y 4 w ee ks t o m o nit or bl o o d c o u nt s 
u ntil t he y rec o ver. 
T he st u d y desi g n is s u m marize d as f oll o ws:  
•  
A 1 4 t o 6 0- da y ( or a ma xi m u m of 3 5 da ys after t h e Scree ni n g 
es o p ha g o gastr o d u o d e n osc o p y [ E G D ], w hic he v er is s h orter) Scree ni n g Peri o d wit h baseli ne 
e val uati o ns f or eli gi bilit y, i ncl u di n g baseli ne disease acti vit y ( b y dail y P R O q uesti o n naire) 
a n d E G D wit h bi o ps y. 
•  
Pri or t o t he first d ose of st u d y dr u g ( 1 2 – 2 4 h o urs pri or t o t he i nf usi o n), s u bjects will be 
pre me dicat e d wit h oral pre d nis o ne ( 4 0 m g if b o d y wei g ht is < 4 0 k g, 6 0 m g if b o d y wei g ht 
is ≥4 0 k g a n d < 6 0 k g, or 8 0 m g if b o d y wei g ht is ≥6 0 k g). 
•  
Eli gi ble s u bjects will  recei ve 6 d oses of A K 0 0 2 ( or place b o) b y I V i nf usi o n o n Da ys 1, 
2 9 ( ± 3), 5 7 ( ± 3), 8 5 ( ± 3), 1 1 3 ( ± 3), a n d 1 4 1 ( ± 3). S u bjects will self-a d mi nister pre d nis o ne 
1 2 – 2 4 h o urs pri or t o t he start of t he first i nf usi o n o nl y. 
•  
S u bjects will re mai n at t he site f or at least 1 h o ur of o bser vati o n after eac h d ose. I n t he 
e ve nt of a n I R R, t he s u bj ect ma y re q uire pr ol o n ge d o bser vati o n ( > 1 h o ur or u ntil t he 
s y m pt o ms res ol ve), as per I n vesti gat or discreti o n. S u bjects will als o be i nstr ucte d t o 
i m me diatel y c o ntact t he st u d y d oct or if a n y reacti o ns occ ur after disc h ar ge. 
•  
A re peat E G D wit h bi o ps y will be perf or me d o n D a y 1 6 9 ( ± 3) or 2 8 ( ± 3) da ys  after last 
d ose if s u bject is ter mi nate d earl y  bet w ee n D a y 2 9 a n d Da y 1 6 9 st u d y visits.  


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n  1 
1 0 N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 6  of 6 6  
C o nfi de nti al  
•  
After c o m pleti o n of t he Da y 1 6 9 visit, t he I n v esti gat or will e val uate w h et h er t he s u bject is 
eli gi ble f or t he O L E Peri o d. 
•  
S u bjects w h o are eli gi ble a n d c h o ose t o partici pate i n t he O L E Peri o d will be gi n f oll o wi n g 
t he O L E Sc he dule of E ve nts o n Da y 1 7 6 ( ± 3). T he O L E Peri o d i ncl u des 6 d oses of 
o pe n-la bel A K 0 0 2 a d mi nistere d o n Da ys 1 7 6 ( ± 3), 2 0 4 ( ± 3), 2 3 2 ( ± 3), 2 6 0 ( ± 3), 2 8 8 ( ± 3), 
a n d 3 1 6 ( ± 3) a n d p ost- tr eat me nt f oll o w- u p visits o n Da y 3 4 4 ( ± 7) a n d Da y 3 7 2 ( ± 7). 
•  
S u bjects w h o are n o t eli gi ble f or ( or w h o c h o ose n ot t o partici pate i n) t he O L E Peri o d will 
be f oll o we d f or a p pr o xi matel y 8 wee ks after t he last d ose per t he Sc he d ul e of E ve nts 
(Ta ble  1). T h e F oll o w- U p Peri o d i ncl u des t he Da y 1 6 9 ( ± 7) visit ( 4 wee ks after t he l ast 
d ose) a n d t he D a y 1 9 7 ( ± 7) visit ( 8 wee ks after t he last d ose). 
•  
If a bs ol ute l y m p h oc yte a n d/ or e osi n o p hil c o u nts ha ve n ot rec o vere d b y t he Da y 1 9 7 visit 
( or t he Da y 3 7 2 visit f or s u bjects partici pati n g i n t he O L E Peri o d), s u bjects will ret ur n 
a p pr o xi matel y e ver y 2 8 da ys f or e xte n de d f oll o w- u p u ntil c o u nts ha ve rec o vere d. 
•  
T otal st u d y d urati o n is a p pr o xi matel y 3 3 – 3 6 wee ks or 5 8 – 6 1 wee ks f or s u bjects 
partici pati n g i n  t he O L E Peri o d, t h o u g h t he st u d y d urati o n c o ul d be e xte n d e d f or 
m o nit ori n g a bs ol ute l y m p h oc yte a n d/ or e osi n o p hil c o u nts (as descri be d a b o ve). 
3. 2  
Sc he d ule of E ve nts  
T he sc he d ule of pr oce d ur es a n d assess me nts (e xcl u di n g t he O L E Peri o d) is de picte d i n Ta ble  1.  
 


Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 7  of 6 6  
C o nfi de nti al  
T a ble 1  
A K 0 0 2- 0 1 4 Sc he d ule of E ve nts 
Descri pti o n  
B aseli ne/  
Scree ni n g 2 
( 1 4 –6 0 d a ys)  
D ose 1  
D a y 1 2 
 
D a y 8  
( ± 1 d a y) 
D a y 1 5  
( ± 2 d a ys) 
D ose 2  
D a y 2 9  
( ± 3 d a ys)3 5 
D ose 3  
D a y 5 7  
( ± 3 d a ys)3 5 
D ose 4  
D a y 8 5  
( ± 3 d a ys)3 5 
D ose 5  
D a y 1 1 3  
( ± 3 da ys)3 5 
D ose 6  
D a y 1 4 1  
( ± 3 da ys)3 5 
D a y 1 6 9  
( ± 3 da ys)3 5 
( or E T3 2) 
E O S  
D a y 1 9 7  
( ± 7 da ys) 
E xte n de d 
F oll o w -U p 3 3  
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p hics a n d Me dical Hist or y  
X  
 
 
 
 
 
 
 
 
 
 
 
St o ol f or O va a n d Parasite 3 
X 
 
 
 
 
 
 
 
 
 
 
 
e P R O Acti vati o n a n d Trai ni n g 4 
X 
 
 
 
 
 
 
 
 
 
 
 
D S Q P R O 5 
D aily fr o m Scree ni n g t hr o u g h E n d of St u dy ( or E T) -------------------------------------------------------------------------------------------------------> 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
E G/ E o D P R O Q uesti o n naire 7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 1 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
 
Baseli ne Diet Assess me nt 9 
X  
 
 
 
 
 
 
 
 
 
 
 
Baseli ne Diet C o m plia nce 9 
 
X 1 
 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
 
B o d y Wei g ht a n d Hei g ht 1 0 
X 
X 1 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
 
Vital Si g ns 1 1 
X 
X 1 
 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
 
1 0 or 1 2 -Lea d E C G 1 2 
X  
 
 
 
 
 
 
 
 
 
 
 
C o m plete P h ysical E xa mi nati o n 1 3 
X 
 
 
 
 
 
 
 
 
 
 
 
E G D wit h Bi o ps y C ollecti o n 1 4 
X 
 
 
 
 
 
 
 
 
X 
 
 
E R E F S Sc ori n g d uri n g E G D 1 5 
X  
 
 
 
 
 
 
 
 
X  
 
 
Bl o o d f or Ser ol o g y 1 6, 1 7 
X 
 
 
 
 
 
 
 
 
 
 
 
Bl o o d f or Ser u m h C G a n d F S H 1 6, 1 8 
X 
 
 
 
 
 
 
 
 
 
 
 
Bl o o d f or T otal Ser u m I g E 1 6, 1 9 
 
X 1 
 
 
 
 
X 1 
 
 
X 
 
 
Bl o o d f or C B C w/ Differe ntial 1 6, 2 0 
X  
X 1 
X  
X  
X 1 
X 1 
X 1 
X 1 
X 1 
X  
X  
X  
Bl o o d f or C he mistr y 1 6, 2 1 
X 
X 1 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
 
Bl o o d f or P K 1 6, 2 2 
 
X 1 
X 
X 
X 1 
X 1 
X 1 
X 1 
X 1 
X 
X 
 
Bl o o d f or A D A 1 6, 2 3 
 
X 1 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
 
X  
 
Bl o o d f or E x pl orat or y A nal ysis 1 6, 2 4 
X  
 
 
X  
 
 
 
 
 
X  
X  
 
Bl o o d f or E x pl orat or y Safet y 1 6, 2 5 
 
X 1 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
 
 
 
C CI
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 8  of 6 6  
C o nfi de nti al  
T a ble 1   
A K 0 0 2- 0 1 4 Sc he d ule of E ve nts c o nt. 
Descri pti o n  
B aseli ne/  
Scree ni n g 2 
( 1 4-6 0 d a ys)  
D ose 1  
D a y 1 2 
 
D a y 8  
( ± 1 d a y) 
D a y 1 5  
( ± 2 d a ys) 
D ose 2  
D a y 2 9  
( ± 3 d a ys)3 5 
D ose 3  
D a y 5 7  
( ± 3 d a ys)3 5 
D ose 4  
D a y 8 5  
( ± 3 d a ys)3 5 
D ose 5  
D a y 1 1 3  
( ± 3 da ys)3 5 
D ose 6  
D a y 1 4 1  
( ± 3 da ys)3 5 
D a y 1 6 9  
( ± 3 da ys)3 5 
( or E T3 2) 
E O S  
D a y 1 9 7  
( ± 7 da ys) 
E xte n de d 
F oll o w -U p 3 3  
Uri ne f or Uri nal ysis 1 6, 2 6 
X 
X 1 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
 
Eli gi bilit y Assess me nt  
X  
X 1 
 
 
 
 
 
 
 
 
 
 
Pre me dicati o n – pre d nis o ne 2 8 
X 1 
 
 
 
 
 
 
 
 
 
 
 
Uri ne Di pstic k Pre g na nc y Test 1 6, 2 7 
 
X 1 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
 
 
 
Access I R T – I P Kit Assi g n me nt 
 
X 1 
 
 
X 1 
X 1 
X 1 
X 1 
X 1 
 
 
 
St u d y Dr u g A d mi nistrati o n 2 9 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
P ost -D ose O bser vati o n 2 9 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
S y m pt o m -Directe d P h ysical E xa m 3 0 
 
X 1 
 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
X 1 
 
Pri or a n d C o nc o mita nt Me dicati o ns  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 3 4 
X  
 
A d verse E ve nts 3 1 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
O pe n -La bel E xte n de d D osi n g 3 4 
 
 
 
 
 
 
 
 
 
X 3 4 
X 3 4  – Da y 1 9 7 visit 
d oes  n ot a p pl y t o  
s u bjects i n O L E peri o d  
A D A:  A nti -dr u g A nti b o d y  
E T:  
Earl y Ter mi nati o n  
F S H:  F ollicle -Sti m ulati n g H or m o ne  
I P: 
I n vesti gati o nal Pr o d uct 
C B C:  C o m plete Bl o o d C o u nt  
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  
P K:  
P har mac o ki netics  
D S Q:  D ys p ha gia S y m pt o m Q uesti o n naire  
E G D:  Es o p ha g o -gastr o -d u o de n osc o p y  
I R T: I nteracti ve Res p o nse Tec h n ol o g y 
P R O:  Patie nt -re p orte d O utc o me 
T a ble 1 N otes  
1)  
Refer t o assess me nt f o ot n ote f or s pecific ti me p oi nts (e. g., pre d ose, d uri n g i nf usi o n, p ost d ose) t o c o n d uct t he assess me nt o n d osi n g da ys.  
2)  
T he scree ni n g peri o d ( Baseli ne) assess me nts ca n be c o n d ucte d o ver m ulti ple da ys wit hi n t he scree ni n g peri o d. T he scree ni n g peri o d m ust be a mi ni m u m of 1 4 da ys ( 2 wee ks) 
a n d n o l o n ger t ha n 6 0 da ys ( or a ma xi m u m of 3 5 da ys  after t he Scree ni n g E G D, w hic he ver is s h orter). Da y 1 ca n be gi n as s o o n as eli gi bilit y criteria are met.  
3)  
Fecal c ollecti o n kits f or O va a n d Parasite will be pr o vi de d t o s u bjects at t he ti me of c o nse nt. St o ol sa m ple s h o ul d be ret ur n e d t o t he cli nical sit e wit hi n 2 4 h o urs of c ollecti o n.  
4)  
At t he ti me of c o nse nt, t he St u d y C o or di nat or will acti vate all e P R O q uesti o n naires i n E D C, pr o vi de t he s u bject wit h a u ni q ue  user na me a n d pass w or d, trai n t he s u bject o n 
dail y D S Q e P R O c o m pleti o n a n d c o m plia nce, a n d e ns u re t he s u bject is a ble t o c o m plete t he 
 q uesti o n naire o n t heir pers o nal electr o nic de vice w hile o n site. 
5)  
S u bjects s h o ul d c o m plete t he D S Q dail y after t he last meal of t he da y. If Q uesti o n 1 is a ns were d “ N o,” t he s u bject s h o ul d a ns wer t he S oli d F o o d  Q uesti o n ( Pr ot oc ol 
A p pe n di x  2) after t he D S Q is c o m plete d a n d s u b mitte d. T he site is res p o nsi ble f or m o nit ori n g c o m plia nce t hr o u g h o ut t he d urati o n of t he  st u d y a n d disc ussi n g c o m plia nce 
d uri n g st u d y visits.  
C CI


Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 1 9  of 6 6  
C o nfi de nti al  
T a ble 1 N otes c o nt.  
6)  
O n Da y -2 ( 2 da ys bef ore Da y 1), o n Da y 1 5 (a p pr o xi matel y 2 wee ks after t he first d ose), a n d o n Da y 2 9 (a p pr o xi matel y 4 wee ks after t he first d ose), s u bjects will 
self-a d mi nister t he 
 after t he y s u b mit t he D S Q (a n d S oli d F o o d Q uesti o n, if a p plica ble). O n Da y 1 5 a n d 
Da y  2 9, s u bjects will als o self -a d mi nister t he 
 after t he D S Q, S oli d F o o d Q uesti o n (if a p plica ble), a n d 
 
7)  
D uri n g t he scree ni n g peri o d o nl y, s u bjects s h o ul d c o m plete t he E G/ E o D P R O q uesti o n naire dail y after c o m pleti o n of t he D S Q (a n d S oli d F o o d Q uesti o n, if a p plic a ble). 
8)  
T he 
 electr o nic q uesti o n naire s h o ul d be t he first assess me nt c o m plete d b y t he s u bject at t he be gi n ni n g of t he st u d y visit pri or t o all ot her st u d y visit assess me nts.  
9)  
A baseli ne diet assess me nt will be perf or me d usi n g t he sta n dar dize d q uesti o ns i n Pr ot oc ol A p pe n di x 7. Eati n g patter ns, f o o d a v oi da nce be ha vi ors, a n d aller gies will be 
ca pt ure d. Per Pr ot oc ol I ncl usi o n Criteria # 7, s u bjects s h o ul d mai ntai n baseli ne diet t hr o u g h o ut t he st u d y. Diet c o m plia nce will be disc usse d d uri n g st u d y visits, a n d a n y 
varia nce will be d oc u me nte d.  
1 0)  Hei g ht (i n c m) a n d wei g ht (i n k g) will be meas ure d at scree ni n g. Wei g ht will als o be meas ure d pre d ose o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, 1 4 1, a n d o n Da ys 1 6 9 a n d 1 9 7 ( or E T).  
1 1)  Vital si g ns will be meas ure d at baseli ne a n d o n Da ys 1, 1 5, 2 9, 5 7, 8 5, 1 1 3, 1 4 1, 1 6 9, a n d 1 9 7 ( or 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), vital si g ns will b e 
meas ure d pre d ose, 1 5 mi n utes ( ± 5 mi n utes) after i nf usi o n start, i m me diatel y p ost d ose ( wit hi n 5 mi n utes after i nf usi o n e n d), a n d 1 h o ur ( ± 5 mi n utes) p ost d ose. S u bject s h o ul d 
be at rest f or ≥5 mi n utes bef ore vital si g ns (s yst olic a n d diast olic bl o o d press u re, p ulse, b o d y te m perat ure, a n d res pirat or y rate) are meas ure d. 
1 2)  Baseli ne E C G s h o ul d be perf or me d after t he s u bject has bee n i n t he s u pi ne p ositi o n f or ≥5 mi n utes a n d, if d o ne o n t he sa me da y as bl o o d c ollecti o n, d o bef ore bl o o d is dra w n.  
1 3)  A c o m plet e 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.  
1 4)  A n E G D wit h bi o ps y c ollecti o n will be perf or me d d uri n g scree ni n g a n d at Da y 1 6 9 ( ± 3 da ys). E G D bi o psies will be c ollecte d, pr ocesse d, a n d s hi p pe d i n acc or da nce wit h 
Pr ot oc ol A p pe n di x 9, t he la b ma n ual, a n d t he hist ol o g y m a n ual. Da y  1 6 9 bi o ps y res ults will be bli n de d. If E T occ urs after Da y 2 9 a n d bef ore Da y 1 6 9, a n E G D wit h bi o ps y 
c ollecti o n s h o ul d be d o ne 2 8 ( ± 3) da ys after t he last d ose (as part of t he E T visit, see Ta ble N ote 3 2 ). If resc ue t hera p y is re q uire d, a n E G D ( bi o ps y a n d E R E F S) m ust be d o ne 
pri or t o i nitiati o n of resc ue me dicati o n or at t he ti me of e mer ge nc y dilati o n (i nstea d of at Da y 1 6 9).  
1 5)  D uri n g t he Scree ni n g E G D a n d Da y 1 6 9 E G D, se verit y will be e val uate d usi n g t he E o E Refere nce Sc ore f or E n d osc o pic A b n or malities per t he st u d y hist ol o g y ma n ual.  
1 6)  Please see t he st u d y ce ntral la b orat or y ma n ual f or c ollecti o n, pr ocessi n g, a n d s hi p me nt i nstr ucti o ns. If p ossi ble, sa m ples s h o ul d be s hi p pe d o n t he sa me da y as c ollecti o n.  
1 7)  Bl o o d f or ser ol o g y ( He patitis B s urface a nti ge n, He patitis C a nti b o d y, He patitis B c ore a nti b o d y, a n d HI V) will be o btai ne d d uri n g scree ni n g.  
1 8)  F or fe male s u bjects, bl o o d will be o btai ne d d uri n g scree ni n g t o test f or h C G ( pre g na nc y) a n d F S H ( p ost -me n o pa usal  stat us). 
1 9)  Bl o o d f or t otal ser u m I g E will be o btai ne d o n Da ys 1 ( pre d ose), 8 5 ( pre d ose), a n d 1 6 9 or E T, if s u bject earl y ter mi nates bef ore Da y 1 6 9.  
2 0)  Bl o o d f or C B C wit h differe ntial will be o btai ne d at all st u d y visits. O n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, a n d 1 4 1, bl o o d will be dra w n t wice ( pre d ose a n d 1 -h o ur p ost d ose). F or e ver y 
C B C wit h differe ntial bl o o d c ollecti o n e xce pt scree ni n g a n d Da y 1 ( pre d ose), t he bl o o d c o u nt res ults will be bli n de d t o t he S p o ns or a n d t he site. T he safet y m o nit or ma y 
re q uest a n u nsc he d ule d C B C wit h differe ntial. Bl o o d c o u nts fr o m Da y 1 9 7 will be use d t o deter mi ne if e xte n de d f oll o w -u p is nee de d.  
2 1)  Bl o o d f or c he mistr y will be o btai ne d d uri n g scree ni n g, pre d ose o n d osi n g da ys ( Da ys 1, 2 9, 5 7, 8 5, 1 1 3, 1 4 1), a n d o n Da ys 1 6 9  a n d 1 9 7 ( or E T).  
2 2)  Bl o o d f or P K 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, a n d 1 9 7 ( or E T). Bl o o d will be dra w n pre d ose o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, a n d 1 4 1.  
C CI
C CI
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Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 20 of 66 
Confidential 
Table 1 Notes cont. 
23) Blood for ADA will be obtained predose on Days 1, 29, 57, 85, 113, and 141, on Day 197 (or ET), and in the event of a suspected immunogenicity-related AE. 
24) Blood for exploratory analysis will be obtained during screening and on Days 15, 169, and 197 (or ET). 
25) If an infusion-related reaction results in infusion interruption or cessation, blood for exploratory safety analyses will be obtained within 1–2 hours of symptom onset. 
26) Urine for standard urinalysis will be obtained during screening, as needed (if warranted in the opinion of the Investigator or Subinvestigator), and on Day 197 (or ET). 
27) For females of childbearing potential, urine for dipstick pregnancy test will be collected, tested, and results confirmed predose on Days 1, 29, 57, 85, 113, and 141. 
28) The day before the first dose (12–24 hours prior to the planned infusion start time), eligible subjects will self-administer oral prednisone premedication based on body weight. 
29) Study drug (or placebo) will be administered as a single peripheral IV infusion over ≥4 hours on Day 1, over ≥3 hours on Day 29, and over ≥2 hours for subsequent infusions 
(Days 57, 85, 113, and 141). Refer to the Pharmacy Manual for detailed instructions on preparation, administration, and infusion rate schedule requirements. 
30) If a new or worsening symptom (or clinically significant finding) is observed or reported, the Investigator or designee will perform a symptom-directed physical examination. 
Symptom-directed physical examinations will be performed as needed and may be performed predose, during infusion, and/or postdose (including for possible IRRs).  
31) All AE, including Adverse Events of Special Interest (AESI) and SAE, will be captured beginning from the start of the first infusion. Serious adverse events occurring 
between the time of consent and the start of the first study drug infusion will be reported only if they are assessed to be related to study procedures. For subjects participating 
in the OLE period, AE will be assessed and recorded in the CRF of the AK002-014 treatment period database up until the start of the first open-label infusion during the Day 
176 visit and recorded in the CRF of the AK002-014 OLE period database beginning from the start of the first open-label infusion during the Day 176 visit. 
32) ET visits should be conducted 28 (±3) days after the last dose of study drug or prior to this, if necessary, to ensure compliance with the visit. If a subject discontinues the 
study >28 days after the last dose of study drug, the ET visit should be conducted as soon as possible. If the subject is terminated after Day 29 and before Day 169, the ET 
visit will be performed 28 (±3) days after last dose and the ET visit will follow the Day 169 assessment schedule (including EGD with biopsy collection). If the subject is not 
participating in the OLE period and the ET visit occurs after Day 169, the Day 197 assessment schedule should be followed for the ET visit. See Protocol Appendix 19.12 for 
the OLE Period Schedule of Events for OLE period ET after Day 176. 
33) If absolute lymphocyte and/or eosinophil counts do not recover (to normal range or baseline levels) by Day 197 (or ET), extended follow-up visits are required every 
28 (±3) days) to monitor blood counts until they recover. Extended follow-up visits consist of blood collection for CBC with differential and collection of AESI and SAE. 
34) After completion of the Day 169 visit, the Investigator will evaluate whether the subject is eligible for the OLE period. If the subject is eligible, the subject will be given the 
option to participate in the OLE period beginning approximately 1 week after the Day 169 visit. Approximately 1 week after the Day 169 visit (on Day 176 ±3 days), eligible 
subjects that choose to participate in the OLE period will begin following the OLE Schedule of Events (Protocol Appendix 19.12) and will receive the first open-label AK002 
infusion. For subjects participating in the OLE period, AE and concomitant medications should be collected and recorded in the AK002-014 Treatment Period database up 
until the start of the first open-label infusion during the Day 176 visit. This includes prednisone premedication administered prior to the Day 176 visit of the OLE period, 
which should be recorded in the Concomitant Medications CRF of both the AK002-014 treatment period database and the AK002-014 OLE period database. 
35) Sites should strive to conduct visits within a ±3 day window, but visits conducted within ±7 days are acceptable and are not considered deviations. Visits conducted ±4–7 
days from target visit date should be minimized as much as possible. Any visit conducted outside of the ±3 day window should receive prior written approval from Allakos. 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 1  of 6 6  
C o nfi de nti al  
3. 3  
St u d y Tre at m e nt  
3. 3. 1  
Tre at m e nt, D ose, a n d M o de of A d mi nistr ati o n 
S u bjects will be ra n d o ml y assi g ne d t hr o u g h t he I R T s yste m t o recei ve 1 of 3 d ose re gi me ns i n a 
d o u ble- bli n d fas hi o n: place b o; t he l o w d ose re gi me n ( 1 m g/ k g A K 0 0 2 a d mi nistere d e ver y 
4 wee ks f or 6 d oses); or t he hi g h d ose re gi me n ( 1 m g/ k g A K 0 0 2 f or t he first d ose f oll o we d b y 
3 m g/ k g A K 0 0 2 a d mi nistere d e v er y 4 w ee ks f or t h e 5 s u bse q ue nt d oses). 
S u bjects t hat c o m plete t he ra n d o mize d, d o u bl e- bli n d, place b o- c o ntr olle d treat me nt (all 6 d oses 
of place b o or A K 0 0 2) a n d t he Da y 1 6 9 visit ma y ha ve t he o pti o n t o recei v e 6 d oses of o pe n- la bel 
A K 0 0 2 t hr o u g h partici pati o n i n t he O L E Peri o d of t he st u d y. 
3. 3. 2  
D ur ati o n of St u d y  
T he t otal st u d y d urati o n f or eac h s u bj ect will be eit her 3 3 – 3 6 wee ks or 5 8- 6 1  wee ks, i ncl u di n g 
a n d de pe n di n g o n: 
•  
Scree ni n g Peri o d of 1 4 – 6 0 da ys ( or a m a xi m u m of 3 5 da ys after t h e Scree ni n g E G D, 
w hic he ver is s h ort er) pri or t o st u d y dr u g a d mi nistrati o n. 
•  
Treat me nt Peri o d of 2 4 wee ks ( ± 3 d a ys) be gi n ni n g t he da y of t he first d os e a n d e n di n g 
4 wee ks after t he last d os e  
•  
O pti o nal O pe n- La b el E xte n de d D osi n g Peri o d of 2 8 wee ks ( ± 3 d a ys), or F oll o w- u p peri o d 
of 4 wee ks ( ± 3 da ys). 
3. 3. 3  
Met h o ds of Assi g ni n g S u bjects t o Tre at me nt Gr o u p  
A p pr o xi matel y 3 0 0 s u bjects wit h acti ve E o E will be ra n d o mize d 1: 1: 1 t o recei ve 1 of 3 d ose 
re gi me ns i n a d o u ble- bli n d ma n ner.  
•  
A K 0 0 2 at 1 m g/ k g e ver y 4 wee ks f or 6 d oses 
•  
A K 0 0 2 at 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 a d mi nistere d e v er y 4 wee ks f or 
5 s u bse q ue nt d oses 
•  
6 d oses of place b o 
3. 4  
Bli n di n g  
T his is a d o u ble- bli n d st u d y. T he i de ntit y of acti ve a n d place b o treat me nts will n ot be k n o w n t o 
I n v esti gat ors, S p o ns or, researc h staff, s u bjects, or t he st u d y m o nit or. O nl y t he u n bli n de d st u d y 
p har macist , t he u n bli n de d p har mac y m o nit or, a n d t he u n bli n de d safet y m o nit or will k n o w t he 
treat me nt assi g n me nt. 


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
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Allakos Inc. 
Page 22 of 66 
Confidential 
3.5 
Hypotheses 
The hypothesis to be tested in the study is that AK002 is different from placebo with regards to 
the 2 co-primary efficacy endpoints of the proportion of subjects who achieve a peak esophageal 
intraepithelial count of ≤6 eosinophils/hpf at Week 24 and the mean reduction from baseline in 
DSQ score at Weeks 23–24. 
3.6 
Determination of Sample Size 
To achieve statistical significance for the first co-primary endpoint, a sample size of 8 subjects 
per treatment group will provide 90% power to demonstrate a statistically significant difference 
between AK002 and placebo in achieving the histological response (defined as the peak 
esophageal intraepithelial eosinophil count ≤6 cells/hpf) at Week 24. This calculation is based on 
the AK002-003 study in which 90% of AK002 subjects and 10% of placebo subjects achieved 
the histologic response at Day 99. The hypothesized treatment effect of 80% yielded a small 
number of subjects per group for the first co-primary endpoint. 
To achieve statistical significance for the second co-primary endpoint, a sample size of 
86 subjects per treatment group will provide 90% power to demonstrate a statistically significant 
difference between any AK002 dose group and placebo treatment group in mean absolute change 
in DSQ score from baseline to Weeks 23–24. This calculation is based on the baseline score of 
30 ± 15 (mean ± Standard Deviation [SD]) reported in the literature, and an expected mean 
reduction of 15 in the AK002 group and 7.5 in the placebo group, and a SD of 15 for the change 
from baseline (Dellon, 2021; Hirano, 2019; Hudgens, 2017). 
Consequently, approximately 100 subjects per treatment group will be included for a total of 
300 subjects, driven by the second co-primary endpoint and a potential 14% dropout rate. 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 3  of 6 6  
C o nfi de nti al  
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 ns 
 
Ter mi n ol o g y  
Defi niti o n  
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 first d ose of 
st u d y dr u g. T his i ncl u des la b tests c ollecte d o n Da y 1 Pre d ose as a n e xa m ple. 
Baseli ne D S Q sc ore is deter mi ne d fr o m 1 4 da ys pr i or t o t he first d ose. 
C o m pleter f or t he St u d y  
A s u bject w h o d oes n ot partici pate i n t he O L E peri o d a n d w h o c o m pletes visits 
t hr o u g h t he Da y 1 9 7 visit or, if a p plica ble, t he last E xte n de d F oll o w -U p visit after 
c o m pleti n g Da y 1 9 7, will be rec or de d as ha vi n g c o m plete d t he d o u ble -bli n d p orti o n 
of t he st u d y.  
A s u bject w h o c o m pletes visits t hr o u g h t he Da y 1 6 9 visit a n d partici pates i n t he 
O L E peri o d of t he st u d y will be rec or de d as ha vi n g c o m plete d t he d o u ble -bli n d 
p orti o n of t he st u d y.  
A s u bject w h o partici pates i n t he O L E peri o d of t he st u d y a n d c o m pletes visits 
t hr o u g h t he Da y 3 7 2 visit or, if a p plica ble, t he last E xte n de d F oll o w -U p visit after 
c o m pleti n g Da y 3 7 2 will be rec or de d as ha vi n g c o m plete d t he O L E p orti o n of t he 
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.  
D S Q  
D ys p ha gia S y m pt o m Q uesti o n naire: See A p pe n di x 1  f or t he D S Q  a n d t he D S Q  
sc ori n g al g orit h m. 
E G/ E o D S u bject -Re p orte d 
O utc o me ( P R O)  
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 uenc y:  
•  
A b d o mi nal pai n i nte nsit y  
•  
Na usea i nte nsit y  
•  
V o miti n g i nte nsit y  
•  
V o miti n g fre q ue nc y  
•  
Diarr hea i nte nsit y  
•  
Diarr hea fre q ue nc y  
•  
Earl y satiet y i nte nsit y  
•  
L oss of a p petite i nte nsit y  
•  
Bl oati n g i nte nsit y  
•  
A b d o mi nal cra m pi n g i nte nsit y  
Eac h i nte nsit y e val uati o n is sc ore d o n a scale of 0 = n o ne t o 1 0 = w orst p ossi ble.  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 4  of 6 6  
C o nfi de nti al  
T a ble 2   
Ter mi n ol o g y a n d Defi niti o ns c o nt. 
Ter mi n ol o g y  
Defi niti o n  
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.  
 
: See A p pe n di x 1 . 
E R E F S  
E o E E n d osc o pic Refere nce Sc ore : See A p pe n di x 1 . 
Ne wl y I nitiate d Me dicati o n  R efers t o a n y me dicati o n wit h start date ≥ St u d y Da y 1 . 
Pri or 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 start date pri or 
t o St u d y Da y 1. 
P R O T S S  
T otal S y m pt o m Sc ore  is t he s u m of 6 wee kl y a vera ge s y m pt o m i nte nsit y sc ores 
(a b d o mi nal pai n, a b d o mi nal cra m pi n g, bl oati n g, na usea, earl y satiet y, a n d l oss of 
a p petite) . 
T E A E  
Treat me nt -e mer ge nt a d verse e ve nts re p orte d i n t he cli nical data base wit h a date of 
o nset o n or after  t he start date of t he first d ose of t he st u d y dr u g.  
Tiss ue E osi n o p hil  
Res p o n der  
F or s u bjects w h o ac hie ve a pea k es o p ha geal i ntrae pit helial c o u nt of 
≤6  e osi n o p hils/ h pf at Wee k 2 4  
Treat me nt Res p o n der  
S u bjects w h o ac hie ve a pea k es o p ha geal i ntrae pit helia l c o u nt of ≤6 e osi n o p hils/ h pf 
at Wee k 2 4 a n d ac hie v e > 3 0 % re d ucti o n i n bi wee kl y D S Q sc ore at Wee ks 2 3 – 2 4.  
St u d y Da y  
St u d y Da y 1 is defi ne d as t he date o n w hic h a s u bject t o o k t he first d ose of St u d y 
Dr u g. Ot her st u d y da ys are defi ne d relati ve t o St u d y Da y 1. F or visits pri or t o t he 
first d ose of St u d y Dr u g, St u d y Da y is calc ulate d as Visit D ate – Da y 1 Date. F or 
visits after t he first d ose, St u d y Da y is calc ulate d as Visit D ate  – Da y 1 Date  + 1.  
St u d y Dr u g  
A K 0 0 2 or place b o a d mi nistere d b y I V i nf usi o n.  
St u d y Wee k  
D efi ne d as 7 da ys a wee k starti n g fr o m t he da y of first d ose ( Da y 1).  
4. 2  
T ar get of Esti m ati o n 
T he esti ma n d (tar g et of esti mati o n) f or Pr ot oc ol A K 0 0 2- 0 1 4 is:  
 
 
I n s u bjects wit h active E o E , w h at is bet wee n gr o u p ( A K 0 0 2 vs. Pl ace b o) differe nce i n  t he 
pr o p orti o n of tiss ue e osi n o p hil res p o n ders at Week 2 4, a n d gr o u p differe n ce i n bi weekly 
D S Q fr o m b aseli ne t o Weeks 2 3 – 2 4 as me as ure d b y t he p atie nt re p orte d Dys p h a gi a 
Sy m pt o m Q uesti o n n aire. 
T he secti 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 ( R 1) 
A d de n d u m ( F D A, 2 0 2 1 ). 
4. 2. 1  
P o p ul ati o n T ar gete d b y t he S cie ntific Q uesti o n  
T he p o p ulati o n tar gete d b y t he scie ntific q uesti o n is defi ne d b y t he i ncl usi o n a n d e xcl usi o n 
criteria as part of t he st u d y pr ot oc ol. S u bjects m ust ha ve a cli nical dia g n osis of acti ve E o E. 
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 5  of 6 6  
C o nfi de nti al  
4. 2. 2  
V ari a bles of I nterest ( o r E n d p oi nt) t o be O bt ai ne d f or E ac h S u bject  
t h at is Re q uire d t o A d dress t he Scie ntific Q uesti o n 
T he c o - pri mar y e n d p oi nts t o be o btai ne d f or eac h s u bject i n t his st u d y t o a d dress t he scie ntific 
q uesti o n are tiss ue e osi n o p hil res p o n ders (as defi ne d i n Ta ble 2) at Wee k 2 4 a n d c ha n g e i n D S Q  
fr o m baseli ne t o Wee ks 2 3– 2 4 as meas ure d b y t he patie nt  re p orte d o ut c o me ( P R O) 
q uesti o n naire. 
4. 2. 3  
Tre at m e nt  
A K 0 0 2 or place b o a d mi nistere d t o s u bjects o n Da ys 1, 2 9, 5 7, 8 5, 1 1 3, a n d 1 4 1. 
4. 2. 4  
I nterc urre nt E ve nts 
T he e ve nts bel o w are c o nsi dere d i nterc urre nt e ve nts (I C E) c o nf o u n di n g wit h t he efficac y 
o utc o mes. 
•  
Pre mat ure disc o nti n uati o n fr o m t he st u d y  
•  
Use of pr o hi bite d/res c ue me dicati o n 
•  
A n y t hera pe utic E G D ( d efi ne d as dilatati o n or ot h er i nter ve nti o n f or a narr o wi n g or 
strict ure of t he es o p ha g us) at a n y p oi nt d uri n g t he st u d y t hr o u g h Wee k 2 4. 
F urt her clarifi cati o n a n d ha n dli n g of I C E i ncl u di n g pr o hi bite d/resc ue me di cati o ns is detaile d i n 
A p pe n di x 2 .  
4. 2. 5  
Str ate g y f o r H a n dli n g I nterc urre nt E ve nt s 
Per t he st u d y pr ot oc ol, if a pr o hi bite d me dicati o n is starte d d uri n g t he c o urs e of t he st u d y, t he 
s u bject will be wit h dra w n fr o m st u d y treat me nt a n d f oll o we d f or t he 1 2- w ee k f oll o w- u p p eri o d. 
I n a d diti o n, t he f oll o w- u p E G D ma y n ot be perf or me d. T h us, f or an al ysis of t he trial pr o d uct 
esti ma n d, tiss ue e osi n o p hil values a n d D S Q sc ores will be c o u nte d as n o n-res p o n ders f or bi nar y 
varia bles a n d s et t o missi n g f or c o nti n u o us o utc o mes fr o m t he p oi nt w he n a n I C E occ urs. A n 
a p pr o priate m et h o d f or h a n dli n g missi n g data t hr o u g h statis tical m o deli n g (e. g., m ulti ple 
i m p utati o n [ MI]) will be use d (Secti o n s 5. 4. 1 , 5. 4. 2 , a n d 6. 1 1 ). T he esti ma n d will pr o vi de a n 
a ns wer t o t he q u esti o n t hat is cr ucial t o i n di vi d ual s u bjects : 
  
“If I tak e t his st u d y dr u g as part of m y treat me nt re gi me n, wit h o ut a d di n g a n y f urt her 
me dicati o ns or t he use of t hera pe utic e n d osc o pic i nter ve nti o ns t hat ma y i m pact t he 
u n derl yi n g disease or e xit t he st u d y pre mat u rel y, w hat i m pr o ve me nts i n hist ol o g y a n d P R O 
s y m pt o ms mi g ht be a ntici pate d after 2 4 wee ks?” 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 6  of 6 6  
C o nfi de nti al  
4. 2. 6  
S u m m ar y Me as ure  of Esti m a n d  
•  
Perce nt ( a n d 9 5 % c o nfi de nce i nter v al [ CI ]) of s u bjects ha vi n g tiss ue e osi n o p hil res p o nse at 
Wee k 2 4 i n t he A K 0 0 2 a n d place b o treat me nt gr o u ps a n d t he a bs ol ute differe nce (a n d 
9 5 % CI) i n t he per ce nt r es p o n se bet wee n treat me nts. 
•  
L east s q uar es mea n  ( L S M) (a n d sta n dar d err or [ S E]) of c h a n ge fr o m baseli ne t o t he a vera ge 
of Wee ks 2 3 – 2 4 D S Q a n d t he bet wee n treat me nt differe n ce i n t he A K 0 0 2 a n d place b o 
treat me nt gr o u ps L S M. 
5.  
St atistic al Met h o ds  
5. 1  
Ge ner al Met h o d ol o g y  
All statistical a nal yses will be c o n d ucte d usi n g S A S v  9. 4 or later versi o n o n t he Micr os oft 
Wi n d o ws O per ati n g S yste m.  
All C R F data (ra w data) will be c o n verte d i nt o S D T M ( St u d y Data Ta b ul ati o n M o del) datasets, 
w hic h will be use d t o cr eate A Da M ( A nal ysis Dat a M o del) data s ets . T he creati o n of t he S D T M 
a n d A Da M d ata sets will f oll o w t he C DI S C ( Cli nical Data I nterc ha n ge Sta n dar ds C o ns orti u m) 
sta n dar ds a n d t he F D A St u d y Data Tec h ni cal  C o nf or ma nce G ui de. All a n al ysis ta bles a n d 
listi n gs will be create d fr o m t he A Da M data s ets.  
C o nti n u o us data will be s u m marize d usi n g “ n” ( n u m ber of s u bjects wit h n o n- missi n g 
o bser vati o ns), mea n, m e dia n, S D, mi ni m u m val ue, a n d ma xi m u m val ue. Cate g orical data will be 
s u m marize d usi n g t he fr e q ue nc y c o u nt a n d p erce nta ge ( n, %) of s u bjects i n eac h cate g or y. 
N u m ber of s u bjects wit h n o n- missi n g v al ues or n u m ber of s u bjects wit h missi n g val ues (e. g., 
N ot D o ne) will be pr ese nte d, w here a p pr o priate. S u bjects wit h missi n g val ues will n ot c o ntri b ute 
t o t he de n o mi nat or f or perce nta g e cal c ulati o ns, u nless s pecifie d ot her wise. C o u nts of 0 i n a n y 
cate g or y will be prese nte d wit h o ut perce nta g e. All s u m maries will be prese nte d f or i n di vi d ual 
treat me nt gr o u ps. I n a d diti o n, f or s u m mar y of dis p ositi o n a n d s u bject baseli ne c haracteristics, t he 
prese ntati o n will i ncl u de  eac h tr eat me nt gr o u p, t he place b o, a n d t h e o verall st u d y p o p ulati o n.  
T he precisi o n r ules f or t h e prese nt ati o n of s u m mar y statistics will be:  
•  
Sa m ple size ( n, N) a n d n u m ber of missi n g res p o nses (if dis pla ye d): I nte g er 
•  
Mea n, c o nfi d e nce i nter val, a n d me dia n: Sa me n u m ber  of deci mal place s as 
re p orte d/c ollecte d 
•  
Sta n dar d de viati o n: Sa me n u m ber  of d eci mal places as re p orte d/c ollecte d  
•  
Perce ntiles, mi ni m u m, ma xi m u m : Sa me n u m ber of deci mal places as re p ort e d/c ollecte d  


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 7  of 6 6  
C o nfi de nti al  
•  
O d ds Rati o : 2 deci mal places  
•  
Perce nta g e : 1 deci mal pl ace g e nerall y, or 2 deci m al places f or < 0. 1 %, or n o deci mal places 
f or 0 % a n d ≥1 0 0 % 
•  
P- val ue: 4 deci mal places  
•  
W B C : 2 deci mal places as 0. 0 1 × 1 09/ L 
•  
Hei g ht/ Wei g ht/ B MI : 1 d eci mal place  
T he data s u m maries will be acc o m pa nie d b y i n di vi d ual s u bject data li sti n gs. All data a vaila ble 
fr o m q uesti o n naires, e C R F, a n d e xter nal tra nsfer (la bs) will be liste d a n d will i ncl u de rele va nt 
s u bject i nf or mati o n, e. g., treat me nt gr o u p a n d st u d y da y. T he listi n gs will be s orte d i n t he or der 
of treat me nt gr o u p, s u bject I D, assess me nt n a me , a n d date/ti me.  
Dates will be pres e nte d i n t he I S O - 8 6 0 1 f or mat Y Y Y Y-M M -D D . Ti mes will be dis pla ye d i n 
2 4- h o ur cl oc k f or mat. N u m beri n g f or ta bles, fi g ures a n d listi n gs will f oll o w I C H E 3 G ui deli ne  
(I C H, 1 9 9 6). 
Alter nati ve met h o ds of a nal ysis of t he data ma y b e c o nsi dere d pri or t o data base l oc k s h o ul d 
s o me of t he ass u m pti o ns u n derl yi n g t he pr o p ose d a nal yses n ot be met. Reas o n f or de part ure 
fr o m the pla n ne d met h o ds will be d oc u me nte d as a n a me n d me nt t o t he S A P or i n t he C S R. 
5. 2  
Visit Wi n d o w a n d U nsc he d ule d Assess me nts  
Data c ollecte d f or st u d y assess me nts pr o vi de i nf or mati o n o n t he stat us of t he s u bject at a gi ve n 
ti me p oi nt. T hese ma y pr o vi de biase d res ults if t he assess me nt is perf or m e d earl y or lat e. 
T heref ore, assess me nts will be sl otte d i nt o a nal ysis wi n d o ws t o all o w s u m maries t o be 
perf or me d f or s u bjects wit h si milar st u d y dr u g e x p os ure. T he a nal ysis wi n d o w is c o nstr ucte d b y 
t he me dia ns of 2 tar g et st u d y da ys of t he a djace nt pla n ne d visits. 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 2 8  of 6 6  
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 5 4  
Da y 1 6 9  
Da y 1 5 5 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 4  
Da y 1 6 9  
Da y 1 5 5 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


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 29 of 66 
Confidential 
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, a 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 
Visit Description 
Window 
Baseline 
On or Prior to Day 1 Predose 
Day 1 
Predose on Day 1 
Day 15 
Day 1 Postdose to Day 18 
Day 29 
Day 21 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 186 
Day 197 
Day 187 to End of Study 


 
Protocol AK002-014 
Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 30 of 66 
Confidential 
5.3 
Adjustment for Covariates 
Efficacy analyses will be adjusted for baseline values and randomization stratum using analysis 
of covariance (ANCOVA), mixed model for repeated measures (MMRM), or Cochran-Mantel-
Haenszel (CMH) 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 post-baseline unscheduled visit prior to missing. If no 
eosinophil count is collected post-baseline, the subject will be considered treatment failure for 
tissue eosinophil response.  
5.4.2 
Missing Daily PRO Scores at Weeks 23–24 
The PRO daily scores will be set to missing if they are collected after subjects have experienced 
an ICE. For the endpoint of change in the biweekly DSQ score, the biweekly average score will 
be calculated using the available daily scores. The validated DSQ calculation normalizes the 
missing daily scores within the 14-day, biweekly interval.  
Missing DSQ scores during Weeks 23–24 will be imputed using the MCMC method. Baseline 
tissue eosinophil count and baseline DSQ and age strata will be included along with the average 
biweekly DSQ (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. Missing data imputation (PROC MI) will be 
conducted separately for active AK002 treatment groups. An example of the SAS code for this 
imputation follows. 
 
proc mi data=DSQ seed=1357986420 nimpute=50  
out=DSQ_IMMPUTED ; 
 
by TRTMT ; 
 
class AGE_STRATA; 
 
mcmc chain=multiple impute=full initial=em nbiter=200 niter=100 ; 
var B_EOS B_DSQ DSQ_W01_02 DSQ_W03_04  
... DSQ_W21_22 DSQ_W23_24 ; 
run ;  
After imputation, the LSM and 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. 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 3 1  of 6 6  
C o nfi de nti al  
T hese  s y nt hesize d L S M a n d S E are t he n us e d i n t he h y p ot hesis test f or t he bet wee n treat me nt 
differe n ce. A n e xa m ple of t he S A S c o de f or t h e s y nt hesiz e d L S M c o m paris o ns bet wee n 
treat me nt is as f oll o ws. 
 
o d s  o u t p u t  P a r a m e t e r E s t i m a t e s = L S M D I F  ;  
p r o c  m i a n a l y z e  d a t a = L S M D I F F  a l p h a = 0 . 0 5  ;  
     b y  t r t m t ;  
 
m o d e l e f f e c t s  L S M  ;  
 
s t d e r r  S E  ;  
r u n  ;  
5. 4. 3  
Missi n g or P arti al D ates of A d verse E ve nts  or C o nc o mit a nt Me dic ati o ns 
A d verse e ve nt s wit h i nc o m plete start or st o p dates (i.e., eit her d a y or m o nt h is missi n g) will be 
c o nsi dere d tr eat me nt -e m er ge nt  a d v erse e ve nts  ( T E A E) u nless t he partial start date or t h e st o p 
date c o nfir ms t he A E starte d or e n de d pri or t o St u d y Da y 1 (e. g., t h e da y of t he A E start date is 
u n k n o w n b ut t he m o nt h a n d year i n dicat e t hat t he A E starts pri or t o St u d y Da y 1). A d v erse 
e ve nts wit h missi n g relati o ns hi p t o st u d y dr u g will be i ncl u de d i n t he “ Relate d” cat e g or y f or t h e 
s u m mar y ta bles a n d f o ot n ote d. Ad verse e ve nt s wit h missi n g se verit y will n ot be i ncl u de d i n t he 
b y- se verit y s u m mar y ta bl e b ut will be f o ot n ote d i n t he ta ble. 
W he n t her e is i nc o m plete i nf or mati o n re g ar di n g d osi n g dates f or pri or a n d c o nc o mita nt 
me dicati o n, t he me dicati o n will be c o nsi dere d as a c o nc o mita nt me dicati o n u nless it c o ntra dicts 
wit h t he st o p date. F or e x a m ple,  a me dicati o n will be c o nsi dere d a pri or m e dicati o n if t he m o nt h 
a n d year of t he e n d d ate i n dicates a dat e bef ore St u d y Da y 1 e ve n t h o u g h t he start date c o ul d be 
missi n g .  
5. 5  
I nteri m A n al ysis 
N o i nteri m a nal ysis is pla n ne d.  
5. 6  
Ti mi n g of Fi n al A n al yses 
T here will be 2 d ata base l oc ks f or t his st u d y: 
•  
A pr o visi o nal data base l o c k after all patie nts c o m plete t he Da y 1 6 9 visit t o all o w f or t he 
a nal ysis of saf et y a n d efficac y dat a t hr o u g h Da y 1 6 9. 
•  
A fi nal data bas e l oc k after all patie nts c o m plete t h e st u d y t o all o w f or t he a nal ysis of a n y 
safet y data c ollecte d after Da y 1 6 9.  
F or eac h dat a base l o c k, a p plica ble E D C data will be l oc ke d i n or der t o pr ot ect write access after 
t he f oll o wi n g prec o n diti o ns are f ulfille d: 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 3 2  of 6 6  
C o nfi de nti al  
•  
All rec or ds are e ntere d i n t he data base.  
•  
All A E are c o de d  t o t he s atisfacti o n of t he C hief Me dical Offi cer. 
•  
All me dicati o ns are c o de d t o t he satisfacti o n of t h e C hief Me dical Officer.  
•  
All data q ueries h a ve bee n res ol ve d.  
•  
All decisi o ns ha ve bee n ma de re g ar di n g all pr ot o c ol vi olati o ns a n d I T T p o p ulati o n 
e xcl usi o ns. 
•  
Writte n a ut h orizati o ns t o l oc k t he data bas e are o bt ai ne d fr o m Alla k os Cli nical Data 
Ma na ge me nt a n d t h e C hief Me dical Officer.  
T he ra n d o mizati o n c o de f or t his st u d y will n ot be re veal e d u ntil t he pre vi o us prec o n diti o ns are 
f ulfille d a n d d oc u me ntati o n of t he pr o visi o nal data base l oc k is c o m plete. After t he pr o visi o nal 
data base l oc k, t h e ra n d o mizati o n c o de will be ma de a vaila ble t o a restrict e d n u m ber of 
i n di vi d uals at Alla k os w h o are i n v ol ve d i n t he a n al ysis of data. Data a nal ysis will c o m me nce 
after t he pr o visi o nal data l oc k a n d t he fi nal dat a bas e l oc k, res p ecti vel y. I n a d diti o n, t he P K a n d 
A D A data ma y b e l oc ke d a n d assesse d s e paratel y.  
5. 7  
M ultice nter St u d y  
S u p ple me ntal a nal ysis will be perf or me d  p o oli n g d ata acr oss st u d y sites. 
T he st u d y will ha ve a p pr o xi matel y 9 0 sites. A nal ysis of site effect  will be base d o n a nal ysis 
ce nters. A n al ysis ce nters will be f or me d i n s uc h a wa y t hat t here are s uffici e nt s u bjects per 
p o ole d a nal ysis ce nter f or t he assess me nt of site effects. Sites fr o m t he f oll o wi n g ge o gra p hic 
cl usters ha ve b ee n i de ntifie d f or p o oli n g data acr o ss st u d y sites: 
•  
A n al ysis Ce nter 1 : Mass ac h usetts, C o n nectic ut, R h o de Isla n d, Ne w Y or k, Ne w 
Jerse y, Pe n ns yl va nia, District of C ol u m bia, Mar yla n d, Mai ne, V er m o nt, Dela ware, a n d 
Ne w Ha m ps hir e  
•  
A n al ysis Ce nter 2 : Vir gi nia, West Vir gi nia, S o ut h Car oli na, Ge or gia, Mississi p pi, Fl ori da, 
Ala ba ma, L o uisia na 
•  
A n al ysis Ce nter 3 : N ort h Car oli na, Te n nessee, O hi o, Mic hi ga n, I n di a na, Ke nt uc k y 
•  
A n al ysis Ce nter 4 : S o ut h Da k ota, Ar k a nsas, Mi n nes ota, Wisc o nsi n, N ort h Da k ota, Illi n ois, 
Miss o uri, I o w a, Te xas, O kla h o ma, Ka nsas, N e bras ka, W y o mi n g, C ol ora d o; 
•  
A n al ysi s Ce nter 5 : Uta h, Ne w Me xic o, Ariz o na, Calif or nia, Ore g o n, Was hi n gt o n, I da h o, 
Ha waii, Alas k a, M o nta na, Ne va da 
•  
A n al ysis Ce nter 6:  R O W  – sites i n A ustralia  a n d t he Net herla n d s 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 3 3  of 6 6  
C o nfi de nti al  
5. 8  
M ulti ple C o m p aris o ns/ M ulti plicit y A dj ust me nt   
A hierar c hical pr o ce d ure will be use d t o c o ntr ol t he o verall T y p e I err or rat e at 0. 0 5 f or t he 
pri mar y e n d p oi nt a n d t he sec o n dar y e n d p oi nts acr oss t he 2 A K 0 0 2 d ose re gi me ns vs. place b o. 
Eac h h y p ot hesis will be f or mall y teste d o nl y if t he prece di n g h y p ot hesis is si g nifica nt at t he 2-
si de d 0. 0 5 si g nifica nce le vel. T he hier arc hical testi n g or der (all c o m paris o ns are wit h t he 
place b o) is as f oll o w: 
T a ble 7 
H y p ot hesis Testi n g Or der Hier a rc h y  
E n d p oi nt Descri pti o n  
A K 0 0 2 I V D ose Gr o u ps  
L o w D ose  
Hi g h D ose  
Pri m ar y E n d p oi nts  
 
 
1)  
T he pr o p orti o n of s u bjects w h o ac hie ve a pea k es o p ha geal i ntrae pit helial c o u nt 
of ≤6  e osi n o p hils/ h pf at Wee k 2 4 . 
8 
1 
2)  
Mea n c ha n ge i n D S Q sc ore fr o m Baseli ne t o Wee ks 2 3 – 2 4 . 
Sec o n d ar y E n d p oi nts  
 
 
1)  
Perce nt c ha n ge i n pea k es o p ha geal i ntrae pit helial e osi n o p hil c o u nt at Wee k 2 4 . 
1 4  
7 
2)  
Pr o p orti o n of s u bjects ac hie vi n g pea k es o p ha geal i ntrae pit helial e osi n o p hil 
c o u nt of ≤1 e osi n o p hil/ h pf at Wee k 2 4 . 
9 
2 
3)  
Pr o p orti o n of s u bjects ac hie vi n g pea k es o p ha geal i ntrae pit helial e osi n o p hil 
c o u nt of < 1 5 e osi n o p hils/ h pf at Wee k 2 4 . 
1 8  
1 7  
4)  
Pr o p orti o n of treat me nt res p o n ders w he n a res p o n der is a s u bject ac hie vi n g 
> 3 0 % re d ucti o n i n s y m pt o ms ( D S Q) at Wee ks 2 3 – 2 4 a n d ac hie vi n g a pea k 
i ntrae pit helial e osi n o philic c o u nt of ≤6 e osi n o p hils/ h pf at Wee k 2 4 . 
1 0  
3 
5)  
Pr o p orti o n of s u bjects wit h > 5 0 % re d ucti o n i n D S Q sc ore fr o m Baseli ne t o 
Wee ks  2 3 – 2 4 . 
1 2  
5 
6)  
Perce nt c ha n ge i n D S Q sc ore fr o m Baseli ne t o Wee ks 2 3 – 2 4 . 
1 1  
4 
7)  
C ha n ge i n bi wee kl y mea n D S Q o ver ti me. 
1 6  
1 5  
8)  
C ha n ge i n E o E E n d osc o pic Refere nce Sc ore fr o m Baseli ne t o Wee k 2 4 . 
1 3  
6  
5. 9  
E x a mi n ati o n of S u b gr o u ps 
Ke y e n d p oi nts will be s u m marize d b y s u b gr o u p t o assess t he c o nsiste nc y of t he treat me nt effect 
acr oss s u b gr o u ps. S u b gr o u ps t o be c o nsi dere d are:  
•  
Ge n der ( Male, Fe male)  
•  
A ge  ( 1 2 – 1 7, ≥1 8) 
•  
Race ( W hite, N o n -W hite)  
•  
Baseli ne D S Q ( ≤3 0, > 3 0)  


 
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6. 
Statistical Analysis 
6.1 
Analysis Populations 
The population of “all screened subjects” comprises subjects who signed the informed consent 
form (ICF). 
6.1.1 
Safety Population 
The safety population comprises randomized subjects who have received at least 1 dose of the 
study drug.  
6.1.2 
Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as subjects who were randomized to treatment. 
6.1.3 
Modified Intent-to-Treat Population 
The Modified Intent-to-Treat (MITT) population is defined as subjects who were randomized 
and received at least 1 dose of 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: 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 3 5  of 6 6  
C o nfi de nti al  
•  
S u bject wit h dre w c o nse nt 
•  
L ost t o f oll o w- u p 
•  
A d mi nistrati ve reas o n  
•  
A d verse e ve nt  
•  
I n v esti gat or decisi o n 
•  
Fail ure t o f oll o w r e q uire d st u d y pr oce d ures 
•  
Ot her  
S u bject dis p ositi o n will be s u m marize d f or all e nr olle d s u bjects. S u bject c o u nts f or t he Safet y , 
M I T T, a n d P P p o p ulati o ns will be i ncl u de d i n t he ta ble. A data listi n g f or s u bject dis p ositi o n will 
be prese nt e d f or all e nr olle d s u bjects.  
6. 3  
Pr ot oc ol D e vi ati o ns 
Pr ot oc ol de viati o ns will i ncl u de, b ut are n ot li mite d t o : 
•  
N o n -c o m plia nce wit h sc he d ule d st u d y visit  
•  
N o n -c o m plia nce wit h st u d y treat me nt  
•  
Recei ve d pr o hi bite d me dicati o ns (see Pr ot oc ol Secti o n 8. 1) 
•  
N o n -c o m plia nce wit h st u d y i ncl usi o n or e xcl usi o n criteria 
•  
N o n -c o m plia nce wit h st u d y assess me nt pr oce d ures  
S u bjects wit h maj or pr ot oc ol de viati o ns will be liste d . T he listi n g will i ncl u de a brief descri pti o n 
of t he de viati o n, de viati o n cate g or y, a n d if a p plica ble, st u d y da y w he n de vi ati o n occ urre d al o n g 
wit h ot her perti ne nt i nf or mati o n. 
If warra nte d b y t h e sa m ple size , s u bjects ( n a n d %) wit h maj or pr ot oc ol de viati o ns will be 
ta b ulate d b y treat me nt gr o u p a n d b y de viati o n cat e g or y. 
S u bjects w h o are e xcl u de d fr o m t he P P p o p ulati o n will be liste d wit h reas o ns f or e xcl usi o n.  
6. 4  
De m o gr a p hics a n d B aseli ne S u bject C h ar acteristics  
Descri pti ve statistics f or s u bject c har acteristics a n d baseli ne val ues will be prese nte d f or all 
p o p ulati o ns b y treat me nt gr o u p a n d b ot h treat me nt gr o u ps c o m bi ne d. C o nti n u o us varia bles will 
be s u m marize d wit h n, m ea n, S D, a n d me dia n. Cat e g orical varia bles will be s u m marize d wit h n 
a n d % of s u bjects f or eac h cate g or y f or t he MI T T a n d P P p o p ulati o ns. 


 
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6.5 
Baseline Disease Characteristics 
Baseline disease characteristics including demographics, baseline DSQ score, and medical 
history 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 
ICF will be tabulated by the Medical Dictionary for Regulatory Activities (MedDRA) 
(version 21.0) System Organ Class (SOC) and Preferred Term (PT). 
6.7 
Electrocardiogram 
A listing of 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 the last dose minus the date of the first dose, plus 1 (date of last dose – date of first 
dose +1). 
Duration of exposure will be summarized using descriptive statistics (n, mean, SD, median, 
minimum, and maximum).  
Treatment compliance is defined as the number of infusions subjects received divided by 6 (i.e., 
total number of infusions expected) × 100%. Treatment compliance will be summarized 
descriptively. In addition, overall compliance that includes adherence to the 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.  


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 3 7  of 6 6  
C o nfi de nti al  
6. 1 0. 2  Pri or , C o nc o mit a nt, a n d Ne wl y Initi ate d  Me dic ati o ns  
Pri or me dicati o ns a n d c o nc o mita nt me dicati o ns will be e xtracte d fr o m t he Pri or/ C o nc o mita nt 
Me dicati o n C R F . Me dicati o ns ta ke n pri or t o St u d y Da y 1 will be c o nsi dere d as pri or 
me dicati o ns , me dicati o ns ta ke n o n or after St u d y Da y 1 will be c o nsi dere d as c o nc o mita nt 
me dicati o ns , a n d ne wl y i nitiate d me dicati o n refe rs t o a n y me dicati o n wit h a start date ≥ St u d y 
Da y 1 . We n ot e t hat a  pri or me dicati o n ma y als o b e a c o n c 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 t he e n d date is o n/aft er St u d y Da y 1. Me dicati o ns will be c o de d usi n g 
W H O Dr u g Dicti o nar y ( W H O D D M arc h 2 0 1 8 release) f or P T a n d A n at o mical T hera p e utic 
C he mical  ( A T C) classifi cati o n .  
M e dicati o ns will be ta b ulate d se paratel y bas e d o n t he Safet y p o p ulati o n. T h e n u m ber ( n a n d %) 
of s u bjects ta ki n g at least 1 me dicati o n a n d t he n u m ber ( %) of s u bjects ta ki n g eac h me di cati o n at 
t he P T  le vel will be ta b ulate d b y A T C 4 a n d P T. S u bjects ta ki n g t he sa me P T me dicati o n t wice 
will o nl y be c o u nte d o nce. 
A s u bject data listi n g will be pr o vi de d t o i ncl u de t he re p ort e d me dicati o n n a me, t he W H O D D 
P T, A T C 4, st u d y da y, a n d perti ne nt s u bject i nf or mati o n. 
A se par ate data listi n g will i ncl u de s u bjects w h o ha ve recei ve d pr o hi bite d me dicati o ns. 
6. 1 1  
A n al ysis of Pri m ar y Effic ac y E n d p oi nts 
T o assist t he data i nter pr etati o n, all I C E will be liste d wit h perti ne nt s u bject i nf or mati o n ( s u bject 
I D, date of l ast i nf usi o n, I C E start/st o p da y, n at ure of I C E [reas o n f or treat me nt/st u d y 
disc o nti n uati o n if a p plica ble, descri pti o n of A E, d escr i pti o n of pr o hi bite d/restricte d me dicati o n ]), 
baseli ne tiss ue e osi n o p hil c o u nt a n d D S Q , a n d m ost rece nt tiss ue e osi n o p hil c o u nt a n d 2-wee k 
a vera g e of D S Q ). 
A s u m mar y ta ble will be creat e d t o prese nt b y treat me nt gr o u p n u m ber of s u bjects ( n, %). 
•  
S u bjects wit h  a n y I C E 
− S u bjects b y I C E cate g or y 
6. 1 1. 1  A n al ysis of t he First C o -Pri m ar y E n d p oi nt  
T he first c o - pri mar y e n d p oi nt will be a nal yze d usi n g t he i m p ute d data set (Secti o n 5. 4. 1 ). 
Fis her’s e xact test (pri mar y  a nal ysis) will be c o n d ucte d c o m pari n g A K 0 0 2 wit h place b o f or t h e 
pr o p orti o n of tiss ue e osi n o p hil res p o n ders. Pr o p orti o n of res p o n ders a n d t he ass ociate d 9 5 % CI 
will be prese nte d f or eac h treat me nt gr o u p. T he b et wee n gr o u p differe nce ( pair wise c o m p aris o n 
wit h place b o) a n d t h e ass ociate d 9 5 % CI  will als o be c o m p ute d a n d prese nt e d. A sa m ple S A S 
c o de is as f oll o ws. 


 
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* 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 ; 
6.11.2 
Sensitivity Analysis of the First Co-Primary Endpoint 
Sensitivity analysis may be carried out using the CMH test stratified by the randomization 
stratification factors (baseline DSQ and age) to assess robustness of 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 DSQ_Strata*AGE_STRAT*TRTP*RESP / cmh commonriskdiff  
(cl=NEWCOMBE) ; 
run ; 
The rationale for specifying Fisher’s exact test as the primary analysis as opposed to specifying 
the CMH test is because when a stratum has 100% response for 1 treatment group and 0% 
response for another treatment group, the CMH test may lose efficiency or not be computable. 
This is evident from the Phase 2 study outcome. 
6.11.3 
Subgroup Analysis of the First Co-Primary Endpoint  
Analysis comparing AK002 and placebo will use 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 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, baseline 
DSQ and age 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. 


 
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Statistical Analysis Plan – Version 1 
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6.11.5 
Sensitivity Analyses of the Second Co-Primary Endpoint 
The 2 sensitivity analyses planned below are constructed based on the already imputed bi-weekly 
data set from Section 5.4.2. From this imputed data set, the bi-weekly DSQ is set to missing if it 
is derived from the daily scores collected on/after ICE event. 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 
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 Age_Grp B_DSQ DSQ_W01_02 DSQ_W03_04 ... DSQ_W21_22 
DSQ_W23_24; 
 
monotone reg; 
 
mnar model(DSQ_W01_02 DSQ_W03_04 ... DSQ_W21_22 DSQ_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 DSQ 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 level of improvement or worsening due to ICE will be added 
to the imputed DSQ. An example of the SAS code follows.  
 
proc mi seed=579864 nimpute=10; 
 
class AGE_STRAT TRTMT; 
 
var B_EOS B_DSQ DSQ_W01_02 DSQ_W03_04 ... DSQ_W21_22 DSQ_W23_24; 
 
monotone reg; 
 
mnar  adjust(DSQ_W01_02 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
adjust(DSQ_W03_04 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
. . . 
 
 
adjust(DSQ_W21_22 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
adjust(DSQ_W23_24 / adjustobs=(TRTMT='1') shift=&d1.)  
 
 
adjust(DSQ_W01_02 / adjustobs=(TRTMT='0') shift=&d0.)  
 
 
adjust(DSQ_W03_04 / adjustobs=(TRTMT='0') shift=&d0.)  
 
 
. . . 
 
 
adjust(DSQ_W21_22 / adjustobs=(TRTMT='0') shift=&d0.)  
 
 
adjust(DSQ_W23_24 / adjustobs=(TRTMT='0') shift=&d0.); 
run; 


 
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Statistical Analysis Plan – Version 1 
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Note: A positive adjustment (shift>0) will increase (worsen) the DSQ score and a negative 
adjustment (shift<0) will reduce (improve) the DSQ score. 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.  
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 described in Section 6.11.2 will be repeated for the PP population. 
Additional analysis will investigate the treatment effect on DSQ 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 DSQ will be 
plotted by treatment group to demonstrate consistency of the treatment effect.  
6.12 
Analysis of Secondary Efficacy Endpoints  
6.12.1 
Percent Change in Tissue Eosinophil Count 
The percent change in peak esophageal intraepithelial eosinophil count at Week 24 will be 
analyzed using ANCOVA with treatment as a factor, baseline eosinophil counts and age strata 
as covariates. The LSM, SE, and 95% CI for individual treatment groups and the LSM, SE, 
95% CI, and p-value for the between treatment difference will be presented. 
6.12.2 
Proportion of Subjects Achieving Peak Esophageal Intraepithelial Eosinophil 
Count of ≤1 and <15 Eosinophils/hpf at Week 24  
These 2 endpoints will be analyzed using Fisher’s exact test similar to the analysis for the first 
co-primary endpoint (Section 6.11.1). 


 
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6.12.3 
Proportion of Treatment Responders  
Treatment responder is defined as >30% improvement in DSQ at Weeks 23–24 and a peak 
esophageal intraepithelial eosinophil count ≤6 cells/hpf at Week 24. This endpoint will be 
analyzed using Fisher’s exact test similar to Section 6.11.1.  
6.12.4 
Proportion of Subjects with >50% Improvement in DSQ from Baseline 
to Weeks 23–24  
This endpoint will be analyzed using the CMH test stratified by the randomization stratification, 
age, and baseline DSQ factors.  
6.12.5 
Percent Change in DSQ from Baseline to Weeks 23–24 
This endpoint will be analyzed using similar methods for the change in DSQ score as discussed 
in Section 6.11.4.  
6.12.6 
Change in Biweekly Mean DSQ Over Time 
The data  will be analyzed using the MMRM with age, treatment, week, and treatment-by-week 
interaction as fixed factors, baseline DSQ (continuous) as covariates, and subject as repeated 
measure unit over time. The model will use change from baseline in the biweekly DSQ from 
Weeks 1–2 through Week 23–24.  
The model variance-covariance matrix will be unstructured. If the computation does not 
converge, the covariance matrix will take the form of Toeplitz, AR(1), and compound symmetry, 
whichever converges first. The improved Kenward-Rodger’s method (SAS KR2 option) will be 
used to derive the denominator degrees-of-freedom. The LSM and 95% CI for the between group 
difference (active dose vs. placebo) will be estimated using the simple contrast at each week.  
A sample SAS code is provided as follows. 
 
proc mixed data=ADEF method=REML ; 
 
class TRTPN USUBJID WEEKS ; 
 
model CHG = B_DSQ AGE_STRAT TRTPN WEEKS TRTPN*WEEKS / ddfm=KR2 ;  
 
repeated WEEKS / subject=USUBJID(TRTPN) type=UN ; 
 
lsmeans TRTPN*WEEKS / pdiff cl ;  
run ; 
6.12.7 
Change in EoE Endoscopic Reference Score  
Change in EREFS from baseline to Week 24 will be analyzed using ANCOVA with age strata, 
treatment, and baseline EREFS.  


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 2  of 6 6  
C o nfi de nti al  
T he E R E F S is t he s u m of 5 c o m p o ne nts wit h a ma xi m u m sc ore of 9 f or eac h l ocati o n ( pr o xi mal 
a n d distal  es o p ha g us) a n d ma xi m u m c o m bi ne d sc ore of 18. I n di vi d ual c o m p o ne nt sc ore ra n ges 
are as f oll o ws:  
•  
E de ma   
0 – 1 
•  
Ri n gs   
0 – 3 
•  
E x u dates  
0 – 2 
•  
F urr o ws   
0 – 2 
•  
Strict ure Ra n ge   0 – 1 
Eac h c o m p o ne nt is sc ored base d o n t he prese nce a n d/ or gra de of eac h feat ure . Miscella ne o us 
feat ur es will n ot be i ncl u de d i n t he t otal sc ore. 
I m pr o v e me nts i n i nfla m mat or y a n d re m o d eli n g feat ures ma y als o be re p orte d base d o n 
i n di vi d ual sc ores f or e d e ma, ri n gs, f urr o ws, e x u date, a n d strict ure. 
I nfla m mat or y a n d fi br oste n otic s u bsc ores will be ge nerat e d ( pr o xi mal, dist al, a n d c o m bi ne d). 
T he i nfla m mat or y s u bsc ore is t he s u m of t he e x u d ate, e de m a, a n d f urr o ws s c ores (ra n ge 0 – 5). 
T he fi br oste n otic s u bsc or e is t he s u m of t he ri n gs a n d strict ure sc ores (ra n g e 0 – 4).  
6. 1 3  
A n al ysis of E x pl or at or y E n d p oi nts 
C ha n ge i n c o nti n u o us e x pl orat or y e n d p oi nts c ollecte d at m ulti ple p ost -baseli ne ti me p oi nts will 
be a nal yze d usi n g M M R M a n d will i ncl u de fi xe d effects f or a g e, bas eli ne val ue, treat me nt, visit , 
a n d t he treat ment- b y- visit i nteracti o n a n d all o w f or ra n d o m s u bject effects. Treat me nt a n d wee k 
will eac h be fitte d as cate g orical vari a bles. T he m o del will ass u me u nstr uct ure d c o varia nce 
str uct ure. 
6. 1 3. 1  C h a n ge i n 
 
C ha n ge i n t he f oll o wi n g c o m p o ne nts of t he  
 fr o m b aseli ne t o Wee k 2 4 will be re p orte d 
i n a descri pti ve ma n n er: 
•  
 
C ha n ge i n t he f oll o wi n g c o m p o ne nts of t he  
 fr o m baseli ne t o Wee k 2 4 ma y be assesse d 
p ost- data base l oc k i n a d diti o n t o calc ulati o n of a t otal  
 sc ore: 
•  
 
 
C CI
C CI
C CI
C CI
C CI
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 3  of 6 6  
C o nfi de nti al  
6. 1 3. 2  C h a n ge i n 
 
C ha n ge fr o m b as eli ne i n 
 s u m mar y (i ncl u di n g D o mai n ) sc ores will be a nal yze d usi n g 
 
baseli ne 
 v al ue  as c o variate, a n d s u bj ect as re peate d m eas ure u nit o ver visits . 
6. 1 3. 3  C h a n ge i n 
 
C ha n ge fr o m bas eli ne i n t he n u m ber of 
 will be a nal yze d usi n g 
 a n d b aseli ne 
 as 
c o variate.  
6. 1 3. 4  
 
Met h o d s f or 
 a n d 
 
 a n al ysis are des cri be d i n a s e parat e 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 bas e d o n t he Safet y p o p ulati o n. A K 0 0 2 
c o nce ntr ati o ns w ill 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 B L O Q ( bel o w li mit of q ua ntificati o n) will be i n dicate d i n t he listi n g.  
Plas ma c o nce ntr ati o ns will be s u m marize d at eac h n o mi nal ti me p oi nt se p aratel y f or eac h 
treat me nt. T he f oll o wi n g descri pti ve statistics will be prese nt e 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 m e pa ge. Mea n plas ma c o n ce 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 s e mi-l o garit h mic scale, wit h t he 
ass ociate d S E  (f or li near scale o nl y) at eac h s c he d ule d ti me p oi nt. 
In t he pl ot, c o n ce ntr ati 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 v al ue of half  t he L L O Q (l o wer li mit of q ua ntificati o n) if t he y are c ollect e d 
p ost d ose.  
A nal ysis of P K para met ers are s p ecifie d s e 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 
t he A E , a n d 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). 
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 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 4  of 6 6  
C o nfi de nti al  
T he treat me nt -e mer g e nt a d verse e ve nts ( T E A E) will be s u m marize d b y t h e n u m ber a n d 
perce nt a ge ( n a n d %) of s u bjects i n eac h S O C a n d P T.  
F or s u m maries b y relati o ns hi p t o st u d y dr u g, “ p ossi bl y relate d” will be c o m bi ne d wit h “relate d ”, 
a n d “ u nli kel y/re m otel y r elate d” will be c o m bi ne d wit h “ n ot relate d.” W he n m ulti ple A E are 
re p orte d wit h t he sa m e P T , t he A E of t he str o n gest relati o n t o st u d y dr u g will be i ncl u de d i n t he 
s u m mar y b y relati o ns hi p, a n d t he A E of t he m ost s e vere gra d e will be i ncl u de d i n t he s u m mar y 
b y se verit y ta ble. 
T he f oll o wi n g A E i nci de nce ta bles will be prese nt e d.  
•  
O ver vie w of T E A E t o i n cl u de 
− N u m ber ( %) of s u bjects w h o re p orte d at least 1 T E A E  
− N u m ber ( %) of s u bjects w h o re p orte d at least 1 treat me nt-relate d T E A E 
− N u m ber ( %) of s u bjects w h o re p orte d at least 1 se vere T E A E 
− N u m ber ( %) of s u bjects w h o re p orte d at least 1 seri o us T E A E  
− N u m ber ( %) of s u bjects w h o re p orte d at least 1 T E A E lea di n g t o treat me nt 
disc o nti n uati o n  
− N u m ber ( %) of s u bjects w h o re p orte d at least 1 T E A E lea di n g t o st u d y disc o nti n uati o n  
− N u m ber ( %) of s u bjects 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 P T  s orte d b y d ecreasi n g or der of s u bject i nci de nce i n t he c o m bi n e d treat me nt 
gr o u p 
•  
T E A E b y S O C a n d P T  i n al p ha betical or d er 
•  
T E A E b y S O C, P T , a n d ma xi mu m se verit y  
•  
T E A E b y S O C , P T , a n d str o n gest relati o ns hi p t o st u d y dr u g  
•  
T E A E lea di n g t o treat me nt disc o nti n uati o n b y S O C a n d P T, if warra nte d b y sa m ple size 
•  
T E A E lea di n g t o st u d y disc o nti n uati o n b y S O C a n d P T, if warra nt e d b y sa m ple size 
•  
Seri o us T E A E b y S O C a n d P T , if warra nt e d b y sa m ple size 
•  
T E A E SI b y S O C a n d P T 
All A E will be liste d wit h o nset/st o p da y, relati o ns hi p t o st u d y dr u g, se verit y, acti o n ta ke n, a n d 
o utc o me. Perti ne nt s u bject i nf or mati o n i ncl u di n g treat me nt gr o u p a n d d e m o gra p hics will als o be 
i nclu de d.  


 
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Separate listings will be provided for TEAE leading to study discontinuation, TEAESI, and 
treatment-emergent SAE (TESAE).  
6.15.2 
Laboratory Test 
Laboratory data will be summarized by presenting summary statistics of raw data and change 
from baseline values (means, medians, SD, 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 visits 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: 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, SD, ranges) for each visit (per analysis window) and time 
point. A data listing will include vital signs from all visits.  
6.15.4 
Electrocardiograms 
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. 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 6  of 6 6  
C o nfi de nti al  
7.  
V ali d ati o n  
Cli nical O perati o ns  a n d Data Ma na g e me nt at All a k os will w o r k wit h t he E D C/ Data Ma na g e me nt 
( D M) ve n d or t o e ns ure t h at t he data c ollecte d f or t he st u d y are of t he hi g hest q ualit y p ossi ble. 
T he st u d y m o nit or will be res p o nsi ble f or re vie wi n g a n d verif yi n g t he acc urac y of t h e data 
rec or d e d o n t he el ectr o ni c case re p ort f or ms (e C R F) directl y fr o m s o urce d oc u me nts at t he 
i n vesti gati ve site. T he D M ve n d or will be res p o nsi ble f or perf or mi n g e dit c hec ks a n d re vie wi n g 
all data e nter e d i nt o t he electr o nic data b ase t o i de ntif y discre pa nt a n d/ or i n c o nsiste nt val ues a n d 
t o se n d q ueries t o t he cli nical sites. T he I n vesti gat or will be res p o nsi ble f or a ns weri n g q ueries 
a b o ut discre pa nt d ata a n d pr o vi di n g electr o nic si g nat ures t o c o nfir m d ata i nte grit y.  
T he pr o gra m mi n g of ta bl es, listi n gs, a n d fi g ures ( T L F) bas e d o n t he cli nical data is o uts o urce d . 
Alla k os see ks t o e ns ur e t he q ualit y of t he re p orts pr o vi de d b y t he C R O i n t he f or m of T L F 
passi n g a ri g or o us vali dati o n pr ocess as f oll o ws :  
•  
Deri ve d dat asets will be i n de pe n de ntl y re pr o gra m me d b y a sec o n d pr o gra m mer. T he 
se parat e datasets pr o d u ce d b y t he 2 pr o gra m mers m ust matc h 1 0 0 %.  
•  
Ta bles will be i n de pe n d e ntl y re pr o gra m me d b y a sec o n d pr o gra m mer, a n d t he res ults fr o m 
b ot h pr o gra ms m ust matc h.  
•  
Fi g ures will be c h ec k e d f or c o nsiste nc y a g ai nst c orres p o n di n g ta bles a n d listi n gs or 
i n de pe n de ntl y re pr o gra m me d if t here are n o c orres p o n di n g ta bles or listi n gs.  
•  
Listi n gs will be c hec ke d f or c o nsiste nc y a gai nst c orres p o n di n g ta bles, fi g ures, a n d deri ve d 
datasets.  
All p ost h oc a nal ysis, if acce pte d f or i ncl usi o n i n t he st u d y re p ort, wi ll f oll o w t he sa me q ualit y 
pr ocess as stat e d a b o ve. T he e ntire set of T L F will be c hec k e d f or c o m plet e ness a n d c o nsiste n c y 
pri or t o deli ver y t o Alla k os.  


 
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8. 
References 
Collins M, Martin L, Alexander E, Boyd J, Sheridan R, He H, et al. Newly developed and 
validated eosinophilic histology scoring system and evidence that it outperforms peak 
eosinophil count for disease diagnosis and monitoring. Dis Esophagus, 2017;30:1–8. 
Dellon E, Collins M, Katzka D, Hudgens S, Lan L, Williams J, et al. Improvements in dysphagia 
and pain with swallowing in patients with eosinophilic esophagitis receiving budesonide 
oral suspension. Clin Gastroenterol Hepatol, 2021;19:699–706. 
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. 
Hirano I, Collins M, Assouline-Dayan Y, Evans L, Gupta S, Schoepfer A, et al. RPC4046, a 
monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients 
with eosinophilic esophagitis. Gastroenterology, 2019;156:592–603. 
Hirano I, Moy N, Heckman M, Thomas C, Gonsalves N, Achem S. Endoscopic assessment of 
the oesophageal features of eosinophilic oesophagitis: validation of a novel classification 
and grading system. Gut, 2013;62:489–95. 
Hudgens S, Evans C, Phillips E, Hill M. Psychometric validation of the Dysphagia Symptom 
Questionnaire in patients with eosinophilic esophagitis treated with budesonide oral 
suspension. Journal of Patient-Reported Outcomes, 2017;1:3.1–11. 
International Council for Harmonisation (ICH). Guideline for industry E3, structure and content 
of clinical study reports, July 1996.  


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 8  of 6 6  
C o nfi de nti al  
9.  
A p pe n dices  
9. 1  
A p pe n di x 1:  D ys p ha gia S y m pt o m Q uesti o n naire, 
 
 a n d E o E E n d osc o pic Refere nce Sc ore  
9. 2  
A p pe n di x 2:  I nterc urre nt E ve nts   
9. 3  
A p pe n di x 3:  List of Ta bles, Listi n gs, a n d Fi g ures   
9. 4  
A p pe n di x 4:  E xa m ple S A S C o des   
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 4 9  of 6 6  
C o nfi de nti al  
9. 1  
A p pe n di x 1 : D ys p h a gi a S y m pt o m Q uesti o n n aire , 
 
, a n d E o E E n d osc o pic Refere nce Sc o re   
D ys p h a gi a S y m pt o m Q uesti o n n aire  
 
C CI


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9.1 
Appendix 1 
DSQ, 
, and EREFS cont.  
The DSQ was validated with the following scoring algorithm (Hudgens, 2017). 
CCI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 1  of 6 6  
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 2  of 6 6  
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 3  of 6 6  
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 4  of 6 6  
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 5  of 6 6  
C o nfi de nti al  
C CI


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 5 6  of 6 6  
C o nfi de nti al  
9. 1 
A p pe n di x 1   D S Q, E o E H S S, a n d E R E F S c o nt.  
E o E E n d osc o pic Refere nce Sc ore  (E R E F S ) 
(Hira n o , 2 0 1 3)  
T he E R E F S  is t he s u m of 5 c o m p o ne nts wit h a ma xi m u m sc ore of 9 f or eac h l ocati o n ( pr o xi mal 
a n d distal es o p ha g us) a n d ma xi m u m c o m bi ne d sc ore of 1 8. I n di vi d ual c o m p o ne nt sc ore ra n ges 
are as f oll o ws:  
•  
E de ma   
0 – 1 
•  
Ri n gs   
0 – 3 
•  
E x u dates  
0 – 2 
•  
F urr o ws   
0 – 2 
•  
Strict ure Ra n ge   0 – 1 
Eac h c o m p o ne nt is sc ore d base d o n t he prese nce a n d/ or gra de of eac h feat ure. Miscella ne o us 
feat ur es will n ot be i ncl u de d i n t he t otal sc ore. 
I m pr o v e me nts i n i nfla m mat or y a n d re m o d eli n g feat ures ma y als o be re p orte d base d o n 
i n di vi d ual sc ores f or e d e ma, ri n gs, f urr o ws, e x u date, a n d strict ure.  
I nfla m mat or y a n d fi br oste n otic s u bsc ores will be ge nerat e d ( pr o xi mal, dist al, a n d c o m bi ne d). 
T he i nfla m mat or y s u bsc ore is t he s u m of t he e x u d ate, e de m a, a n d f urr o ws s c ores (ra n ge 0 – 5). 
T he fi br oste n otic s u bsc or e is t he s u m of t he ri n gs a n d strict ure sc ores (ra n g e 0 – 4).  


 
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Statistical Analysis Plan – Version 1 
10 November 2021 
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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 of 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 of prednisone or equivalent) after the screening 
period.  
b) Initiation of systemic or swallowed corticosteroids (≤10 mg/day of 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). 


 
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3) Sodium cromolyn 
a) Discontinuation of a previously stable dose of sodium cromolyn after the screening 
period and before the end of Week 24. 
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. 
Any subject requiring a therapeutic EGD (defined as dilatation or other intervention for a 
narrowing or stricture) that may impact subsequent assessment of the DSQ during the first 
qualifying EGD at the end of the screening period or at any point during the study through 
Study Week 24.  
D. 
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 of 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 patient-reported GI 
symptoms, subjects must meet the entry requirements for both histology and symptom burden 
(DSQ) 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 ICE. For PPI and corticosteroids (≤10 mg/day of 
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 one 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 


 
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Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
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Confidential 
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 a 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 patients 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 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 6 0  of 6 6  
C o nfi de nti al  
9. 3  
A p pe n di x 3: List of T a bles,  Listi n gs, a n d Fi g ures   
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 n e d S u bjects) 
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 haract eristics ( 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 haract eristics ( 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 n ci 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 ( S afet 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 ( S afet y P o p ulati o n) 
Ta ble 1 4. 1. 7. 3  
D urati o n of Tr eat 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 n at o mic T her a p e utic C he mical Classificati o n a n d 
Preferre d Ter m: S u bject I n ci 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 p e utic C he mical 
Classificati o n a n d Preferre d Ter m: S u bject I nci d e n ce ( 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 v al 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 gi a Se verit y Sc ore ( MI T T P o p ulati o n) 
Ta ble 1 4. 1. 1 3  
Baseli ne S u bject Re p orte d O utc o me T otal, S y m pt o m Sc ores a n d D S Q 
Sc ores ( MI T T P o p ulati o n) 
C CI


 
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Statistical Analysis Plan – Version 1 
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9.3 
Appendix 3: List of Tables, Listings, and Figures cont. 
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 Gender Subgroup 
(MITT Population) 
Table 14.2.1.2.2 
Tissue Eosinophil Responder at Week 24 by Age (MITT Population) 
Table 14.2.1.2.3 
Tissue Eosinophil Responder at Week 24 by Race Subgroup 
(MITT Population) 
Table 14.2.1.2.4 
Tissue Eosinophil Responder at Week 24 by Baseline DSQ Subgroup 
(MITT Population) 
Table 14.2.2.1 
Change from Baseline in DSQ: Primary Analysis – Multiple Imputation for 
Missing Biweekly DSQ (MITT Population) 
Table 14.2.2.2 
Change from Baseline in Weeks 23–24 DSQ Scores: Sensitivity Analysis 
1 – Biweekly DSQ 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 Weeks 23–24 DSQ Scores: Sensitivity Analysis 
2 – Biweekly DSQ 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 Weeks 23–24 DSQ Scores – Multiple Imputation 
(Per Protocol Population) 
Table 14.2.2.5.1 
Change from Baseline in Weeks 23–24 DSQ Scores by Gender Subgroup – 
Multiple Imputation (MITT Population) 
Table 14.2.2.5.2 
Change from Baseline in Weeks 23–24 DSQ Scores by Age – Multiple 
Imputation (MITT Population) 
Table 14.2.2.5.3 
Change from Baseline in Weeks 23–24 DSQ Scores by Race Subgroup – 
Multiple Imputation (MITT Population) 
Table 14.2.2.5.4 
Change from Baseline in Weeks 23–24 DSQ Scores by Baseline DSQ 
Subgroup – Multiple Imputation (MITT Population) 
 


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 6 2  of 6 6  
C o nfi de nti al  
9. 3  
A p pe n di x 3: List of T a bles, Listi n gs, a n d Fi g ures c o nt. 
Ta ble 1 4. 2. 3  
Perce nt C ha n ge fr o m Baseli ne t o Wee k 2 4 i n Pea k Es o p ha geal 
I ntr ae pit helial 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  
Pr o p orti o n of S u bjects Ac hie vi n g Pea k Es o p ha g eal I ntrae pit helial 
E osi n o p hils C o u nt ≤1 Cell / h pf at Wee k 2 4 ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 5  
S u bjects Ac hie vi n g Pea k Es o p ha geal I ntrae pit heli al E osi n o p hils C o u nt 
< 1 5  Cells/ h pf at Wee k 2 4 ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 6  
S u bjects Ac hie vi n g Pea k Es o p ha geal I ntrae pit heli al E osi n o p hil a n d D S Q 
Treat me nt Res p o nse at Wee k 2 4 ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 7  
S u bjects wit h > 5 0 % Re d u cti o n i n D S Q fr o m Baseli ne t o Wee ks 2 3 – 2 4 
Ta ble 1 4. 2. 8  
Perce nt C ha n ge fr o m Baseli ne i n D S Q fr o m Baseli ne t o Wee ks 2 3 – 2 4 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 9  
C ha n ge i n Bi wee kl y Mea n D S Q o ver Ti me Usi n g M M R M 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 0 
C ha n ge i n E o E Refere nce Sc ore fr o m Baseli ne t o Wee k 2 4 
( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 1  
C ha n ge i n 
 fr o m Baseli ne t o Wee k 2 4 
( 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  
 – P h ysical C o m p o ne nt S u m mar y 
( MI TT 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  
 – 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 3  
C ha n ge fr o m Baseli ne t o Wee k 2 4 i n 
 ( MI T T P o p ulati o n) 
Ta ble 1 4. 2. 1 4  
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 5  
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 6  
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 7  
S u bject I n ci 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) T est 
( Safet y P o p ulati o n) 
 
C CI
C CI
C CI
C CI


 
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Statistical Analysis Plan – Version 1 
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9.3 
Appendix 3: List of Tables, Listings, and Figures cont. 
Table 14.3.1.1 
Overview of Treatment-Emergent Adverse Events (Safety Population) 
Table 14.3.1.2 
Treatment-Emergent Adverse Events by Preferred Term: Subject Incidence 
(Safety Population) 
Table 14.3.1.3 
Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term: Subject Incidence (Safety Population) 
Table 14.3.1.4 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Maximum Severity: Subject Incidence (Safety Population) 
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 14.2.1 
Cumulative Distribution Function Plot of Change from Baseline in Average 
of Weeks 23–24 DSQ Score 
Figure 14.2.2 
P-value from Between-Treatment Comparison in Weeks 23–24 DSQ – 
Tipping Point Analysis  


 
Pr ot oc ol A K 0 0 2 -0 1 4  
Statistical A nal ysis Pla n – Versi o n 1  
1 0  N o ve m ber 2 0 2 1  
Alla k os I nc.  
Pa ge 6 4  of 6 6  
C o nfi de nti al  
9. 3  
A p pe n di x 3: List of T a bles, Listi n gs, a n d Fi g ures c o nt. 
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 n cl 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 Diseas e 
( 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 
Diet 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  
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  
D ys p ha gia S y m pt o m 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  
D ys p ha gia S y m pt o m Q uesti o n naire – Dail y Sc or e ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 2c  
D ys p ha gia S y m pt o m Q uesti o n naire – Bi wee kl y Sc ore ( Safet y P o p ulati o n) 
Listi n g 1 6. 2. 2. 3 
 
( 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 T e xt 
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 ul ati 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) 
C CI
C CI


 
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Statistical Analysis Plan – Version 1 
10 November 2021 
Allakos Inc. 
Page 65 of 66 
Confidential 
9.3 
Appendix 3: List of Tables, Listings, and Figures cont. 
Listing 16.2.3.1.1 
All Adverse Events (Safety Population) 
Listing 16.2.3.1.2 
Serious Adverse Events (Safety Population) 
Listing 16.2.3.1.3 
Adverse Events with Outcome of Death (Safety Population) 
Listing 16.2.3.1.4 
Adverse Events Leading to Study Drug Discontinuation (Safety Population) 
Listing 16.2.3.1.5 
Adverse Events of Special Interest (Safety Population) 
Listing 16.2.3.2.1 
Clinical Laboratory Tests – Hematology (Safety Population) 
Listing 16.2.3.2.2 
Clinical Laboratory Tests – Blood Chemistry (Safety Population) 
Listing 16.2.3.2.3 
Clinical Laboratory Tests – Urinalysis (Safety Population) 
Listing 16.2.3.2.4 
Clinical Laboratory Tests – Diagnostic Immunology/Molecular Biology 
(Safety Population) 
Listing 16.2.3.2.5 
Clinical Laboratory Tests – Endocrinology (Safety Population) 
Listing 16.2.3.2.6 
Clinical Laboratory Tests – Parasitology (Safety Population) 
Listing 16.2.3.2.7 
Pre-Infusion Blood Collection (Safety Population) 
Listing 16.2.3.3.1 
Substance Use – Alcohol Consumption at Screening (Safety Population) 
Listing 16.2.3.3.2 
Urine Pregnancy Test (Safety Population) 
Listing 16.2.3.4.1 
Study Drug Administration (Safety Population) 
Listing 16.2.3.4.2 
Study Drug Accountability (Safety Population) 
Listing 16.2.3.5 
Vital Signs (Safety Population) 
Listing 16.2.3.6 
Subject Body Size (Safety Population) 
Listing 16.2.3.7.1 
12-Lead ECG Intervals at Baseline (Safety Population) 
Listing 16.2.3.7.2 
12-Lead ECG Overall Interpretation (Safety Population) 
Listing 16.2.3.8 
Physical Examination (Safety Population) 
Listing 16.2.3.9 
Anti-drug (AK002) Antibody (ADA) Test (Safety Population) 
Listing 16.2.3.10.1  Morphological Assessment of Esophageal Biopsy (Safety Population) 
Listing 16.2.3.11 
Serum Concentrations of IgE (Safety Population) 
 


 
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Statistical Analysis Plan – Version 1 
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Page 66 of 66 
Confidential 
9.4 
Appendix 4 Example SAS Codes  
 
/** Multiple Imputation **/ 
proc mi data=DSQ seed=1357986420 nimpute=50 out=DSQ_IMPUTED1 ; 
       by TRTMT ; 
       class DISEASE_STRAT ; 
       mcmc chain=multiple impute=full initial=em nbiter=200 niter=100 ; 
var B_EOS DISEASE_STRAT B_DSQ DSQ_W01_02 DSQ_W03_04... DSQ_W21_22 DSQ_W23_24 ; 
quit; 
/** Recalculate change from baseline **/ 
data DSQ_imputed2; 
   set DSQ_imputed1; 
   chg=DSQ_w23_24 - b_DSQ; 
run; 
 
proc sort data=DSQ_imputed2 out=DSQ_imputed; 
   by _imputation_; 
run; 
 
/** ANCOVA by imputation **/ 
ods output diffs=diffs lsmeans=lsm; 
proc mixed data=DSQ_imputed method=reml; 
   by _imputation_; 
   class TRTMT; 
   model CHG=DISEASE_STRAT B_DSQ 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;