Clinical trial NCT03436797
Conditions: Chronic Urticaria
Sponsor: Allakos Inc.
Start date: 2018-01-23; Completion date: 2020-04-06
Enrollment: 47 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 2a, open-label study to assess the effects of AK002

Detailed description:
This open-label study is to assess the effects of AK002, given as monthly intravenous infusions at up to 3 mg/kg. A total of 47 patients will be enrolled across 2-4 sites. All patients enrolled in the study will receive 6 monthly infusions of AK002 and will then be followed for another 8 weeks. Some patients will have the option to receive an additional 12 months of extended dosing.

Arms: arm 1: AK002 given as monthly intravenous infusions at up to 3 mg/kg.
Interventions: intervention 1: AK002
Intervention descriptions: intervention 1: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs).

Protocol documents:
Prot_002.pdf: 
An Open-Label, Pilot Study to Assess the Efficacy and Safety of AK002 (Siglec-8) in Subjects 
with Antihistamine-Resistant Chronic Urticaria 
NCT Number: NCT03436797 
Document Date: 04 Dec 2018  
German EC Approval Date for Amendment 4.1: 04 Feb 2019 


 
975 Island Drive, Suite 201, Redwood City, CA 94065 
 
Page 1 of 83 
Clinical Research Protocol AK002-006 
An Open-Label, Pilot Study to Assess the Efficacy and Safety of AK002 
(Siglec-8) in Subjects with Antihistamine-Resistant Chronic Urticaria 
Short Title: CURSIG (Chronic Urticaria Response to AK002 (Siglec-8) 
Protocol Number 
AK002-006 
Version and Date 
Original 
01 Aug 2017 
 
Amendment 1 
12 Dec 2017 
Amendment 2 
23 Feb 2018  
Amendment 2.1 
08 Mar 2018 (Germany only) 
 
Amendment 3 
01 May 2018 
 
Amendment 4.1 04 Dec 2018 (Germany only) 
lnvestigational Product 
AK002 
Study Phase 
2a 
EUDRACT Number 
2017-002581-51 
IND Number 
137491 
Sponsor 
Allakos, Inc.  
975 Island Drive, Suite 201, Redwood City, CA 94065 USA 
Medical Monitor  
Name:  
, MD, PhD 
Telephone: 
  
Email:  
 
 
Approval: 
 
4 DEC 2018 
, MD, PhD, 
 
 
Date 
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. 


Protocol AK002-006 
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Investigator Protocol Agreement 
I have read the protocol specified below. In my formal capacity as 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: 
AK002-006 
Protocol Title: 
An Open-Label, Pilot Study to Assess the Efficacy and Safety of 
AK002 (Siglec-8) in Subjects with Antihistamine-Resistant Chronic 
Urticaria 
Original Protocol Date: 
01 Aug 2017 
Amendment 1: 
12 Dec 2017 
Amendment 2 
23 Feb 2018 
Amendment 2.1:  
08 Mar 2018 
Amendment 3: 
01 May 2018 
Amendment 4.1: 
04 Dec 2018 
Investigator: 
Printed Name: 
 
 
 
Signature: 
 
 
 
Date: 
 
 
 


Protocol AK002-006 
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Date: 04 Dec 2018 
Allakos, Inc. 
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Table of Contents 
Clinical Research Protocol AK002-006 ........................................................................................1 
Investigator Protocol Agreement..................................................................................................2 
Table of Contents ...........................................................................................................................3 
List of Figures .................................................................................................................................8 
List of Tables ..................................................................................................................................8 
List of Abbreviations .....................................................................................................................9 
1. 
Protocol Synopsis ................................................................................................................11 
2. 
Background .........................................................................................................................18 
2.1 
Chronic Urticaria ........................................................................................................18 
2.2 
Cholinergic Urticaria ..................................................................................................19 
2.3 
Urticaria Factitia .........................................................................................................20 
2.4 
Chronic Spontaneous Urticaria ...................................................................................21 
2.5 
Current Therapies for CU ...........................................................................................22 
2.6 
Siglec-8 .......................................................................................................................23 
2.7 
Overview of Animal Studies with AK002 ..................................................................24 
2.8 
Overview of Prior Clinical Studies with AK002 ........................................................24 
3. 
Study Design .......................................................................................................................26 
4. 
Objectives ............................................................................................................................26 
4.1 
Primary Objective .......................................................................................................26 
4.2 
Secondary Objectives .................................................................................................26 
5. 
Endpoints ............................................................................................................................27 
5.1 
Primary Endpoint ........................................................................................................27 
5.2 
Other Endpoints ..........................................................................................................27 
6. 
Investigational Plan ............................................................................................................28 
6.1 
Study Design ...............................................................................................................28 
6.1.1 
Screening Period ..........................................................................................28 
6.1.2 
Treatment Period ..........................................................................................29 


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6.1.3 
Follow-Up Period .........................................................................................29 
6.1.4 
Extended Dosing (Optional) .........................................................................29 
6.2 
Rationale for the Study Design ...................................................................................29 
6.3 
Rationale for the Dose/Regimen, Route of Administration, and Duration 
of Treatment ................................................................................................................30 
6.3.1 
Rationale for AK002 Dose and Regimen .....................................................30 
6.3.2 
Rationale for Concomitant Antihistamine Dose and Regimen ....................31 
6.4 
Risks and Benefits ......................................................................................................31 
7. 
Population ...........................................................................................................................31 
7.1 
Rationale for the Number of Subjects ........................................................................32 
7.2 
Inclusion/Exclusion Criteria .......................................................................................32 
7.2.1 
Inclusion Criteria ..........................................................................................32 
7.2.2 
Exclusion Criteria .........................................................................................33 
8. 
Study Treatment .................................................................................................................34 
8.1 
Investigational Treatment ...........................................................................................34 
8.2 
Concomitant Treatment ..............................................................................................34 
8.3 
Treating the Patient .....................................................................................................35 
8.3.1 
Patient Numbering ........................................................................................35 
8.3.2 
Formulation of AK002 .................................................................................36 
8.3.3 
Supply of AK002 to the Investigational Site ...............................................36 
8.3.4 
Preparation of Study Drug ............................................................................36 
8.3.5 
AK002 Administration .................................................................................37 
8.3.6 
Permitted Study Drug Dose Adjustments and Interruptions ........................38 
8.3.7 
AK002 Accountability .................................................................................39 
8.3.8 
Measures of Treatment Compliance ............................................................39 
8.3.9 
Dietary and Lifestyle Restrictions ................................................................39 
8.3.10 
Prohibited Treatments ..................................................................................39 
9. 
Discontinuation and Replacement of Subjects and Major Protocol Deviations ...........41 
9.1 
Definition of Early Termination from the Study ........................................................41 
9.2 
Definition of Study Completion .................................................................................41 
9.3 
Early Discontinuation of Study Drug .........................................................................41 


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9.4 
Withdrawal of Subjects from Study ...........................................................................42 
9.5 
Replacement of Subjects .............................................................................................43 
9.6 
Termination of study ...................................................................................................43 
10. 
Visit Schedule and Assessments ........................................................................................43 
10.1 Information to be Collected on Screening Failures ....................................................47 
10.2 Patient Demographics/Other Baseline Characteristics ...............................................47 
10.3 Treatment Exposure and Compliance .........................................................................47 
10.4 Efficacy Assessments .................................................................................................47 
10.4.1 
Urticaria Patient Daily Diary ........................................................................48 
10.4.2 
Urticaria Control Test ...................................................................................48 
10.4.3 
 ...................................48 
10.4.4 
 .........................................49 
10.4.5 
 .....................49 
10.4.6 
 .................................................49 
10.4.7 
 ..................................................................49 
10.4.8 
 ..............................................50 
10.4.9 
 ..................................................................50 
10.4.10 
 .......................................................................................50 
10.4.11 Symptom-Free Days .....................................................................................50 
10.4.12 Skin Biopsies ................................................................................................50 
10.4.13 Laboratory Evaluations for Efficacy ............................................................51 
10.4.14 Trigger Threshold Tests (FricTest® and Pulse-Controlled Ergometry) ......51 
10.4.15 Measuring Disease Activity and Functional Status ......................................51 
10.5 Safety Assessments .....................................................................................................52 
10.5.1 
Medical Monitoring ......................................................................................52 
10.5.2 
Physical Examination ...................................................................................52 
10.5.3 
Vital Signs ....................................................................................................53 
10.5.4 
Height and Weight .......................................................................................53 
10.5.5 
Laboratory Evaluations for Safety ...............................................................53 
10.5.6 
Hematology ..................................................................................................53 
10.5.7 
Clinical Chemistry ........................................................................................53 
10.5.7.1 Follicle-Stimulating Hormone ................................................................ 53 


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10.5.7.2 Serology .................................................................................................. 54 
10.5.7.3 Anti-Drug-Antibodies ............................................................................. 54 
10.5.7.4 PK Analysis ............................................................................................ 54 
10.5.8 
Urinalysis .....................................................................................................54 
10.5.8.1 Urine Drug Screen and Cotinine Test ..................................................... 54 
10.5.9 
Fecal Collection ............................................................................................54 
10.5.10 Electrocardiogram ........................................................................................54 
10.5.11 Pregnancy Testing ........................................................................................55 
10.5.12 Tolerability/Acceptability ............................................................................55 
10.6 End of Trial .................................................................................................................55 
11. 
Adverse Event Reporting ...................................................................................................55 
11.1 AE Recording .............................................................................................................56 
11.2 AE Severity .................................................................................................................56 
11.3 AE Relationship to Study Drug ..................................................................................57 
11.4 Adverse Events of Special Interest .............................................................................57 
11.5 Serious Adverse Events ..............................................................................................58 
11.6 Adverse Event Reporting Procedures .........................................................................59 
11.6.1 
All Adverse Events .......................................................................................59 
11.6.2 
Serious Adverse Event Reporting ................................................................60 
11.6.3 
Pregnancy Reporting ....................................................................................61 
11.7 Anaphylaxis ................................................................................................................61 
11.8 Medical Monitoring ....................................................................................................62 
12. 
Data Review and Database Management .........................................................................62 
12.1 Site Monitoring ...........................................................................................................62 
12.2 General Safety Monitoring .........................................................................................62 
13. 
Data Analysis ......................................................................................................................63 
13.1 Populations for Analysis .............................................................................................63 
13.1.1 
MITT Population ..........................................................................................63 
13.1.2 
Safety Population .........................................................................................64 
13.1.3 
Per-Protocol Population ...............................................................................64 
13.2 Disposition of Subjects ...............................................................................................64 


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13.3 Protocol Deviations ....................................................................................................64 
13.4 Patient Demographics/Other Baseline Characteristics ...............................................64 
13.5 Treatments (Study Drug, Concomitant Therapies, Compliance) ...............................64 
13.6 Analysis of the Primary Objectives ............................................................................64 
13.6.1 
Primary Efficacy Variable ............................................................................64 
13.7 Analysis of Secondary Objectives ..............................................................................65 
13.7.1 
Secondary Efficacy Variables ......................................................................65 
13.7.2 
Safety ............................................................................................................65 
13.8 Sample Size Calculation .............................................................................................66 
14. 
Data Collection, Retention and Monitoring .....................................................................66 
14.1 Data Collection Instruments .......................................................................................66 
14.2 Data Management Procedures ....................................................................................66 
14.3 Data Quality Control and Reporting ...........................................................................66 
14.4 Archiving of Data .......................................................................................................66 
14.5 Availability and Retention of Investigational Records ...............................................67 
14.6 Data Monitoring ..........................................................................................................67 
14.7 Patient Confidentiality ................................................................................................67 
15. 
Administrative, Ethical, and Regulatory Considerations ...............................................68 
15.1 Protocol Amendments ................................................................................................68 
15.2 Institutional Review Board/Independent Ethics Committees .....................................68 
15.3 Informed Consent Form ..............................................................................................69 
15.4 Publications .................................................................................................................69 
15.5 Clinical Trial Registration ..........................................................................................70 
15.6 Payment to Subjects ....................................................................................................70 
15.7 Investigator’s Responsibilities ....................................................................................70 
16. 
References ...........................................................................................................................71 
17. 
Appendices ..........................................................................................................................74 
17.1 Appendix 1: Sampson’s Criteria for Anaphylaxis ......................................................74 
17.2 Appendix 2: Procedures for Extended Dosing (Optional) ..........................................75 
 


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List of Figures 
Figure 1 
Classification of Chronic Urticaria .............................................................................18 
Figure 2 
CholU Patient after Provocation Test .........................................................................19 
Figure 3 
Antihistamine Updosing only moderately improves Symptoms and 
Quality of Life in CholU Patients ...............................................................................20 
Figure 4 
Patient with Urticaria Factitia: Wheal and Flare Development 10–15 minutes 
after Stroking of the Skin ............................................................................................21 
Figure 5 
Patient with CSU: Spontaneous Wheal, Flare, and Itch .............................................22 
Figure 6 
Potential Pharmacological Targets in T Helper Cell-Driven Diseases .......................23 
 
 
 
List of Tables 
Table 1 
Study Outline ..............................................................................................................28 
Table 2 
Prohibited Treatments .................................................................................................40 
Table 3 
Schedule of Assessments ............................................................................................44 
Table 4 
PRO Instruments for Efficacy Assessment .................................................................48 
Table 5 
 ......................................................................................................50 
Table 6 
Adverse Event Severity Grading ................................................................................57 
Table 7 
Adverse Event Relationship to Study Drug ................................................................57 
Table 8 
Extended Dosing Period .............................................................................................76 
Table 9 
Schedule of Assessments for Extended Dosing ..........................................................81 
 


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List of Abbreviations 
 
 
ADCC 
Antibody-dependent cell-mediated cytotoxicity 
AE 
Adverse event 
 
 
AH 
Antihistamine 
BP 
Blood pressure 
CFR 
Code of Federal Regulations 
CholU 
Cholinergic Urticaria 
 
 
 
 
CINDU 
Chronic Inducible Urticaria 
CIU 
Chronic Idiopathic Urticaria 
CRF 
Case Report/Record Form 
CSU 
Chronic Spontaneous Urticaria 
CTCAE 
Common Terminology Criteria for Adverse Events 
CU 
Chronic Urticaria 
 
 
 
 
ECG 
Electrocardiogram 
ET 
Early Termination 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HbsAg 
Hepatitis B surface antigen 
HIPAA 
Health Information Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgE 
Immunoglobulin E 
IRB 
Institutional Review Board 
IRR 
Infusion-Related Reaction(s) 
 
 
IV 
intravenous administration 
MC 
Mast cell 


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MCID 
Minimal Clinical Importance Difference 
MedDRA 
Medical dictionary for regulatory activities 
NaCl 
Sodium chloride 
NCI 
National Cancer Institute 
NOAEL 
No-observed-adverse-effect level 
PCE 
Pulse-Controlled Ergometry Test 
PID 
Patient Identification Number 
PP 
Per-Protocol population 
PT 
Preferred Term 
QOD 
Every other day 
QoL 
Quality of Life 
RBC 
Red blood cell(s) 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SC 
subcutaneous administration 
 
 
SOC 
System Organ Classification 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
UAS 
Urticaria Activity Score 
UAS7 
Weekly Urticaria Activity Score 
UCT 
Urticaria control test 
UF 
Urticaria factitia 
UPDD 
Urticaria Patient Daily Diary 
VAS 
Visual Analog Scale 
WBC 
White blood cells(s) 
WHO 
World Health Organization 
 


Protocol AK002-006 
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1. 
Protocol Synopsis 
Study Title 
An Open-Label, Pilot Study to Assess the Efficacy and Safety of AK002 
(Siglec-8) in Subjects with Antihistamine-Resistant Chronic Urticaria 
Short Title 
CURSIG (Chronic Urticaria Response to AK002 (Siglec-8)) 
Rationale 
Chronic urticaria (CU) is a skin condition, which is characterized by transient 
pruritic wheal-and-flare-type skin reactions and, in some subjects, the 
occurrence of angioedema. About 1% of the population in Europe has chronic 
or recurrent urticaria (Hellgren, 1972). Subjects with CU are often impaired in 
their quality of life, with negative effects on sleep, daily activities, 
school/work life, and social interactions. 
Therefore, the current guidelines of the European Academy of Allergy and 
Clinical Immunology (EAACI)/Global Allergy and Asthma European 
Network (GA2LEN)/European Dermatology Forum (EDF)/World Allergy 
Organization (WAO) state that the aim of treatment for all types of urticaria is 
to achieve complete symptom relief. 
The current treatment guidelines for the management of all forms of urticaria 
recommend the use of non-sedating oral H1-antihistamines as first-line 
therapy. In more than 50% of subjects, symptoms persist with standard dosing 
of antihistamines. In antihistamine-refractory subjects with chronic 
spontaneous urticaria (CSU), the only currently licensed treatment is 
omalizumab, a monoclonal anti-IgE antibody. In subjects with chronic 
inducible urticaria (CINDU) including cholinergic urticaria (CholU) and 
urticaria factitia (UF), no other licensed drugs are available, and subjects often 
need to be treated with omalizumab, cyclosporin, or other off-label drugs. 
In double-blind placebo-controlled studies in selected antihistamine-refractory 
subjects, omalizumab has been shown to be very effective in the treatment of 
CSU and is recommended as third-line therapy if symptoms persist with 4-fold 
antihistamines. However, some CSU subjects continue to have symptoms 
despite omalizumab treatment or do not respond at all to omalizumab 
treatment. Approximately 60–65% of omalizumab patients continue to 
experience symptoms despite treatment, so there clearly is a need for new and 
better treatments (Saini, 2015). Furthermore, omalizumab is not licensed for 
the treatment of CINDU. There is a significant unmet need for new targeted 
therapeutic options for subjects with CSU and CINDU. 
Study Design/Phase 
This is an open-label, proof-of-concept study. 
Objectives 
To assess the effects of AK002 on symptom control in subjects with chronic 
urticaria. CU subjects will document triggers and symptoms (wheals, pruritus, 
etc.), as well as quality of life (QoL), before, during and after treatment. 
Subjects will also be subjected to standardized provocation tests and 
assessment of symptom development. 


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 Primary Objective 
To assess the efficacy of AK002 on symptoms in subjects with CU (change in 
urticaria control test [UCT] score). 
 Secondary 
Objectives 
The efficacy, safety and pharmacodynamics of AK002 on urticaria symptoms, 
QoL, provocation testing, and histological criteria. 
 
The effects of AK002 in CU subjects will be assessed through the following 
evaluations: 
1) 
Safety and tolerability (adverse events, laboratory safety tests etc.) 
2) 
Disease activity scores (UAS7, 
) 
3) 
 
4) 
Number of symptom-free days 
5) 
Use of rescue medication (up to 3 sgAH tablets/day) 
6) 
Effects on 
 
7) 
Number of 
 
8) 
 
9) 
Changes in trigger thresholds (in CINDU, including CholU) 
10) Rate of 
 
(UCT, 
 
11) Serum levels of potential biomarkers of disease activity and treatment 
responses 
12) Rates of relapse and sustained response during the follow-up period 
Endpoints 
 
 Primary Endpoint 
The primary endpoint is the change in Urticaria Control Test (UCT), a score 
for symptom control in chronic urticaria, from baseline to Week 22 in CU 
subjects after treatment with AK002. A change of the UCT score of 3 or more 
points is regarded as clinically relevant (minimal clinically important 
difference [MCID]). 
 Other Endpoints 
1) 
Safety of subjects treated with AK002: This includes physical 
examination, routine safety laboratory assessments, vital signs, 
electrocardiogram (ECG), urine safety, and adverse event reporting 
(Visits 2–10) 
2) 
Change in disease activity as assessed by UAS7 and/or 
 from 
Baseline to Visits 3, 5, 8, and 10 
3) 
Change in number of symptom-free days per week (patient diary-based 
CSU score; wheals, flares, itch, avoidance behavior) from Baseline to 
Visits 3, 5, 8, and 10 


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 Other Endpoints 
cont. 
4) 
Change in 
 assessed by 
 
 from Baseline to Visits 3, 5, 8, and 10 
5) 
Change in number of intake of rescue medication from Baseline to 
Visits 3, 5, 8, and 10 
6) 
In case of 
, change in 
 from Visit 2 
to Visits 3, 5, 8, and 10, as assessed by 
 
7) 
Change in number of 
 
from Baseline to Visits 3, 5, 8, and 10 
8) 
Change in 
 from Baseline (Day 1) 
to Visits 3, 5, 8, and 10 
9) 
Changes in trigger threshold from Baseline (Day 1) to Visits 3, 5, 8, and 
10, as assessed by Pulse Controlled Ergometry Test (PCE) FricTest®, as 
applicable 
10) Rates of complete response, partial response, and non-response based on 
UCT, 
, trigger thresholds (where applicable), and QoL 
from Baseline to Visits 3, 5, 8, and 10 
11) Serum levels at baseline (Day 1) and change from Baseline to Visits 3, 5, 
8, and 10 of serum levels of potential biomarkers in AK002-treated 
subjects (e.g., tryptase, eosinophils, total IgE, basophils, eosinophil 
cationic protein) 
12) Rates of AK002-treated subjects with relapse, rebound, sustained 
treatment effects at Visit 7 
Study Drug 
AK002 (Siglec-8 inhibitor) 
Dose and Route of 
Administration 
Up to 6 doses of AK002 will be given over the course of the study. AK002 
will be administered as an intravenous (IV) infusion at a dose of 0.3 mg/kg 
given over a period of approximately 4 hours on study Day 1 (Dose 1). If well 
tolerated, dose will be increased to 1 mg/kg, given over a period of 4 hours on 
study Day 29 (Dose 2) and Day 57 (Dose 3) (±2 days). For Doses 4, 5, and 6 
on Day 85, Day 113, and Day 141, respectively, dose will be increased to 
3 mg/kg if patient has UCT score of <12, and/ or at the discretion of the 
Investigator in consultation with the Allakos Medical Monitor.  If the UCT 
score ≥12 and if the Investigator in consultation with the medical monitor feels 
that the patient has received adequate symptom improvement, then the patient 
will continue to receive 1 mg/kg dose. 
Subjects in the CholU, UF, and CSU-XOLAIR® (omalizumab) failure cohorts 
who received all 6 infusions of AK002, were followed at least through 
Day 155, and demonstrated severe symptoms of urticaria following the last 
dose of treatment will be allowed the option to receive extended dosing with 
up to 12 additional doses of AK002 (see Appendix 2). They will have to be 
treated with extended dosing within 6 months of last dose.  


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Dose and Route of 
Administration cont. 
All subjects that decide to receive extended dosing will start with a dose of 
0.3 mg/kg, followed by possible dose increases to 1 mg/kg and 3 mg/kg for 
subsequent infusions. 
The Investigator in consultation with the Medical Monitor may increase the 
dose to 6 mg/kg and then to 10 mg/kg if they think that the patient has not 
received benefit from the lower doses. 
The amount of AK002 to be administered will be calculated based on the 
patient’s body weight determined within 24 hours of each infusion. The 
calculated amount of AK002 (
) based on body weight will be 
diluted with 0.9% NaCl for IV injection. Final combined volume of each IV 
bag of AK002 + 0.9% NaCl will be 120 mL. 
Note: Exactly 100 mL of the calculated dose of AK002 will be administered 
to each patient. The extra 20 mL is to be used to prime the IV infusion line 
during the preparation of the IV line at the bed side. 
It is recommended that each dose of 120 mL is prepared in an empty 
medication delivery bag. The doses for the extension study are outlined in 
Appendix 2. 
Centers/Countries 
Approximately 4 study centers in the USA and Germany. Only the sites in 
Germany will participate in the extension study. 
Number of Subjects 
N (total) = Approximately 48 subjects with chronic urticaria 
This will include the following cohorts: 
• 
Approximately 12 subjects with Cholinergic urticaria (CholU) 
• 
Approximately 12 subjects with Urticaria factitia (UF) 
• 
Approximately 12 XOLAIR® (omalizumab) naïve subjects with Chronic 
spontaneous urticaria (CSU) 
• 
Approximately 12 subjects with Chronic spontaneous urticaria (CSU) 
who did not achieve an adequate response on XOLAIR® (omalizumab) 
in the opinion of the Investigator  
The extended dosing will be applicable only to the subjects in the CholU, UF, 
and CSU-XOLAIR® (omalizumab) failure cohorts. 
Rationale for 
Sample Size 
The planned sample size of approximately 48 subjects is based on common 
practice in early phase, proof-of-concept studies. 
Duration of Patient 
Participation and 
Duration of Study 
The total study duration for each patient will be approximately 32 weeks. This 
includes: 
• 
A screening period of 4 weeks prior to study drug administration 
• 
Administration of study drug at Day 1, Day 29, Day 57, Day 85, 
Day 113, and Day 141 
• 
Follow-up through Day 197 (8 weeks post last dose) 


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Duration of Patient 
Participation and 
Study cont. 
Subjects who elect to receive optional extended dosing with up to 
12 additional doses of AK002 will participate for up to an additional 
12 months (see Appendix 2). 
Inclusion Criteria 
1) 
Adults (≥18 and ≤85 years old) 
2) 
Body weight <125 Kg 
3) 
Informed consent signed and dated 
4) 
Able to read, understand, and willing to sign the informed consent form 
and comply with study procedures 
5) 
Diagnosis of CU for at least 3 months, refractory to antihistamine 
treatment in single or 4-fold dosage. 
6) 
Willing, committed, and able to return for all clinic visits and complete 
all study-related procedures, including willingness to have IV infusion of 
study drug administered by a qualified person  
7) 
Females of childbearing potential must have a negative pregnancy test at 
Baseline. Female subjects must be willing to use highly effective 
contraception (Pearl-4 Index <1) or abstain from sexual activity from 
Screening until the end of the study, or for 120 days following the last 
dose of study drug, whichever is longer. A woman will be considered not 
of childbearing potential if she is post-menopausal for greater than two 
years (FSH >40 mL) or surgically sterile (bilateral tubal ligation, bilateral 
oophorectomy, or hysterectomy). 
 
Male patients with female partners of childbearing potential must agree to 
use a highly effective method of contraception from Screening until the 
end of the study or for 120 days following the last dose of study drug, 
whichever is longer. All fertile men with female partners of childbearing 
potential should be instructed to contact the Investigator immediately if 
they suspect their partner might be pregnant (e.g., missed or late 
menstrual period) at any time during study participation.  
8) 
No participation in other clinical trials 4 weeks before participation in this 
study 
9) 
Uncontrolled CU (UCT <12) at the time of enrollment 
10) For extended dosing, subjects must have a baseline (Day 1) UCT of ≤5 
and a week 22 (Day 155) UCT of ≥ 12 (Complete Response). They must 
have a UCT of ≤5 post-week 22 (Day 155) and by week 44 (Day 309) 
i.e., within 6 months from last dose 
Exclusion Criteria 
1) 
Acute urticaria 
2) 
Concurrent/ongoing treatment with immunosuppressives (e.g., 
cyclosporine, methotrexate, dapsone, or others) within 4 weeks or 
5 half-lives prior to Baseline, whichever is longer 


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Exclusion Criteria 
cont. 
3) 
Significant medical condition rendering the patient immunocompromised 
or not suitable for a clinical trial 
4) 
Significant concomitant illness that would adversely affect the subject’s 
participation or evaluation in this study 
5) 
History of malignancies within five years prior to screening other than a 
successfully treated non-metastatic cutaneous, basal, or squamous cell 
carcinoma and/or in situ cancer 
6) 
Presence of clinically significant laboratory abnormalities 
7) 
Lactating women or pregnant women 
8) 
Substance abuse (drug or alcohol) or any other factor (e.g., serious 
psychiatric condition) within the last 5 years that could limit the subject’s 
ability to comply with study procedures 
9) 
Subjects who are detained officially or legally to an official institute or 
those that have been committed to an institution by virtue of an order 
issued either by the judicial or the administrative authorities will be 
excluded from the study  
10) Use of omalizumab within the last 2 months 
11) Receipt of intravenous IgG therapy 30 days prior to Baseline 
12) Plasmapheresis 30 days prior to Baseline 
13) Use (daily or every other day) of Doxepin 14 days prior to Baseline 
14) Receipt of inactive vaccination or live attenuated vaccine 30 days prior to 
Baseline 
15) Use of H2-antihistamines 7 days before Baseline 
16) Intake of leukotriene antagonists within 7 days prior to enrollment  
17) Intake of systemic corticosteroids (e.g., oral or depot) within 14 days 
prior to enrollment 
18) Positive screening for ova and parasite test at Baseline  
19) Treatment of helminthic parasite within 6 months of screening 
20) Positive HIV serology at screening 
21) Positive Hepatitis serology at baseline, except for vaccinated patients or 
patients with past but resolved hepatitis at screening 
22) Donation or loss of >500 mL of blood within 56 days prior to 
administration of study drug or donation of plasma within 7 days prior to 
administration of drug 
23) Known hypersensitivity to any ingredients of AK002 or drugs related to 
AK002 (e.g., monoclonal antibodies, polyclonal gamma globulin) 


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Concomitant 
Medications 
Second-generation H1-antihistamines as concomitant medication once daily 
and up to 4 times daily on demand (drug intake to be documented in the 
patient diary). 
Safety Evaluations 
Safety and tolerability will be assessed throughout the study by monitoring 
and evaluating adverse events (AEs), including any complications resulting 
from the IV infusion. All treatment-emergent adverse events (TEAEs) will be 
collected from the start of study drug administration through 8 weeks after last 
dose received or Early Termination (ET). Severity will be assessed using the 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) Version 4.03. All AEs will be assigned a severity grade and 
relationship to study drug. 
Additional safety evaluations include clinical laboratory tests, including anti-
drug antibody to AK002, complete blood counts, chemistries, and urinalyses, 
ECGs; and vital signs. 
Statistical 
Methodology 
All subjects who received a dose of study drug will be included in the 
analysis. All safety data will be listed. Where appropriate, summary statistics 
will be provided (number of non-missing values, mean, median, standard 
deviation, minimum, and maximum for continuous variables, and number and 
percentage for categorical variables) for all measures, including demographic 
and baseline values, clinical scores and safety endpoints. 
Rationale for 
Amendment 4.1 
The following modifications have been incorporated into Amendment 4.1 of 
the protocol.  
• 
Procedures that allow subjects in the CholU, UF, and CSU-XOLAIR® 
(omalizumab) failure cohorts who received all 6 infusions of AK002, 
were followed through Day 155, and demonstrated severe symptoms of 
urticaria following discontinuation of treatment, to be offered the option 
to receive extended dosing with up to 12 additional doses of AK002. 
Offering extended dosing allows subjects with no other treatment options 
continued access to AK002 and the benefit obtained during the initial 
6 infusions. It also allows for collection of longer-term efficacy, safety, 
and tolerability data of AK002. 
• 
PK will be analyzed retroactively using backup blood samples. 
 


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2. 
 Background 
2.1 
Chronic Urticaria 
Chronic urticaria (CU) is a skin condition which is characterized by transient pruritic wheal and 
flare type skin reactions and, in some patients, the occurrence of angioedema. In Europe, more 
than 5 million patients are thought to suffer from persisting urticarial symptoms (Maurer, 2011), 
which either occurs spontaneously (i.e., spontaneous urticaria), or can be induced as a result of 
environmental physical stimuli such as pressure, ultraviolet irradiation, heat or cold (physical 
urticaria), or by other means (Metz, 2012). Patients with CU are often severely impaired in their 
quality of life (Mlynek, 2009), with negative effects on sleep, daily activities, school/work life, 
and social interactions. The current guidelines of the European Academy of Allergy and Clinical 
Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European 
Dermatology Forum (EDF)/World Allergy Organization (WAO) state that the aim of treatment 
for all types of urticaria is to achieve complete symptom relief (Zuberbier, 2014). However, most 
patients with chronic spontaneous urticaria (CSU) and all patients with inducible urticaria require 
symptomatic treatment for effective symptom control. Figure 1 shows the classification of 
chronic urticaria. 
 
Chronic urticaria subtypes 
Chronic spontaneous urticaria 
Inducible urticaria 
Spontaneous appearance of wheals, 
angioedema, or both ≥6 weeks due to 
known or unknown causes 
Symptomatic dermographism* 
Cold urticaria† 
Delayed pressure urticaria‡ 
Solar urticaria 
Heat urticaria§ 
Vibratory angioedema 
Cholinergic urticaria 
Contact urticaria 
Aquagenic urticaria 
* Also called urticaria factitia, dermographic urticaria 
† Also called cold contact urticaria 
‡ Also called pressure urticaria 
§ Also called heat contact urticaria 
 
(Zuberbier, 2014) 
Figure 1 
Classification of Chronic Urticaria 
 
 


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2.2 
Cholinergic Urticaria 
Cholinergic urticaria (CholU) is a form of inducible urticaria (Zuberbier, 1994; Godse, 2013) 
that is defined by itching and whealing following the induction of sweating, either actively (e.g., 
exercise) or passively (e.g., hot bath). CholU must be differentiated from exercise-induced 
urticaria/anaphylaxis, which is induced by exercise but not passive warming and is more often 
associated with systemic symptoms. Figure 2 shows a CholU patient after a provocation test. 
 
Figure 2 
CholU Patient after Provocation Test 
CholU is a disorder of young adults and has a high prevalence in this age group (up to 20%) 
(Zuberbier, 1994). CholU patients typically develop itchy pinpoint sized short-lived wheals with 
large flare reactions commonly localized to the limbs and the trunk a few minutes after exercise 
or passive warming. In some patients, emotional stress, or hot and spicy food or beverages can 
also elicit symptoms. Usually, skin lesions last for 15 to 60 minutes. There is a clear association 
with atopy (Zuberbier, 1994; Altrichter, 2016) and bronchial hyperresponsiveness 
(Petalas, 2009) in CholU patients. 
Several recent studies indicate that CholU can be due to an allergy to components of human 
sweat. Some CholU patients show immediate-type hypersensitivity reactions to their own diluted 
sweat after intradermal injections, and basophils from these patients react to autologous sweat 
and release high amounts of histamine in vitro (Petalas, 2009; Takahagi, 2009). In addition, 
CholU patients, but not healthy controls, reportedly express IgE to sweat antigens. Very recently, 
a new allergen component from a fungus was identified in human sweat (Hiragun, 2013). 


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The first line treatment options in CholU are avoidance of eliciting triggers and treatment with 
non-sedating H1-antihistamines. However, many of these patients are not sufficiently treated by 
antihistamines (Koch, 2016) (Figure 3) and these patients often suffer from the symptoms of 
CholU and are impaired in their quality of life. 
 
(Koch, 2016) 
Figure 3 
Antihistamine Updosing only moderately improves Symptoms and 
Quality of Life in CholU Patients 
2.3 
Urticaria Factitia 
Urticaria factitia (UF; also known as dermographic urticaria and symptomatic dermographism) is 
a chronic disease characterized by whealing and itching following a minor stroking pressure, 
rubbing, or scratching of the skin. 
In all patients with a history of wheals after stroking of the skin, a provocation test should be 
performed. This can be done by stroking of the skin lightly with a smooth blunt object (e.g. the 
tip of a closed ball point pen or a wooden spatula) or a purpose-built instrument, known as a 
dermographometer. For the diagnosis of symptomatic dermographism, the smooth blunt object 
should be held perpendicular to the skin and should be used to apply a light stroking pressure to 
the skin of the upper back or volar forearm. The reaction is considered positive in patients who 
show a wheal response and report pruritus at the site of provocation (Figure 4). 
Patients with a positive test reaction should be evaluated for individual pressure thresholds. For 
this purpose, a provocation device (FricTest®) has been developed that allows for reproducible 
and standardized threshold testing. Threshold testing enables physicians to assess disease 
severity and treatment response more precisely. 
 


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Figure 4 
Patient with Urticaria Factitia: Wheal and Flare Development 10–15 minutes 
after Stroking of the Skin 
The majority of patients with urticaria factitia benefit from treatment with non-sedating 
antihistamines. Some patients, however, do not achieve adequate symptom control even with up-
dosing of antihistamines (Borzova, 2008) and may suffer from substantial quality of life 
impairment (Wallengren, 2007). Since even very minor stroking of the skin can lead to the 
development of wheals and severe itching, these patients are limited in their choice of clothing 
and are impaired in their social interactions and partnerships. 
2.4 
Chronic Spontaneous Urticaria 
Chronic spontaneous urticaria (CSU), formerly known by the terms chronic idiopathic urticaria 
and chronic urticaria (CU), is one of the most frequent skin diseases. In CSU itchy, wheal-and-
flare-type skin reactions spontaneously appear on the skin at any time of the day or night 
(Figure 5). These symptoms can also occur several times per day and each skin eruption can 
persist up to 24 hours. At any time, 0.5–1% of the population suffers from the disease 
(Maurer, 2011). Although all age groups can be affected, the peak incidence is seen between 
20 and 40 years of age. The duration of the disease is generally several years but is likely to be 
longer in more severe cases, cases with concurrent angioedema, in combination with physical 
urticaria or with a positive autologous serum skin test (autoreactivity). CSU has detrimental 
effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It 
also has a large impact on society in terms of direct and indirect health care costs, as well as 
reduced performance at work and in private life (Maurer, 2011). In many patients, an underlying 
cause of CSU cannot be identified making a causal and/or curative treatment difficult. 


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Figure 5 
Patient with CSU: Spontaneous Wheal, Flare, and Itch 
2.5 
Current Therapies for CU 
The current treatment guidelines for the management of all forms of urticaria recommend the use 
of non-sedating oral H1-antihistamines as first-line therapy. In more than 50% of the patients, 
symptoms persist with standard dosing of antihistamines (Maurer, 2011). In antihistamine- 
refractory patients with CSU, the only currently licensed treatment is omalizumab, a monoclonal 
anti-IgE antibody. In patients with inducible urticaria, including CU, no other licensed drugs are 
available and patients often need to be treated with omalizumab, cyclosporin, or other off-label 
drugs (Metz, 2014; Metz, Ohanyan, 2014). 
In double-blind placebo-controlled studies in selected antihistamine-refractory patients, 
omalizumab has been shown to be very effective in the treatment of CSU and is recommended as 
third-line therapy if symptoms persist with four-fold antihistamines. However, some CSU 
patients continue to have symptoms despite omalizumab treatment or do not respond at all to 
omalizumab treatment. Furthermore, omalizumab is not licensed for the treatment of chronic 
inducible urticaria (CINDU). Therefore, there is a significant unmet need for new targeted 
therapeutic options for patients with CSU and CINDU. 


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2.6 
Siglec-8 
Siglec-8 is a member of the CD33-related family of Siglecs (sialic acid immunoglobulin-like 
lectins) with a restricted tissue distribution, expressed selectively on the surface of mature 
eosinophils, mast cells, and at lower levels on basophils, but not in early precursors of these cell 
populations or other blood cells (Figure 6). Siglec-8 is expressed at equivalent levels on mast 
cells obtained from peripheral blood and from bone marrow of patients with systemic 
mastocytosis and on resting and activated eosinophils obtained from peripheral blood and from 
several tissues in patients with a variety of atopic disorders, including nasal polyps and asthma 
(Falahati, 2015; Nutku, 2005; Nutku-Bilir, 2008). Engaging Siglec-8 results in the inhibition of 
release of mediators from mast cells without affecting their survival. Therefore, Siglec-8 is a 
novel and promising target for the treatment of mast cell-mediated diseases, especially CU 
(James, 2012). 
 
(Boyman, 2015) 
Figure 6 
Potential Pharmacological Targets in T Helper Cell-Driven Diseases 
Antibody engagement of Siglec-8 on mast cells and eosinophils can result in inhibition of 
mediator release from mast cells and eosinophils. AK002 is a non-fucosylated IgG1 antibody 
with antibody-dependent cellular cytotoxicity (ADCC) activity against Siglec-8 expressing target 
cells. In the presence of effector cells of the immune system, such as natural killer cells, the 
antibody also shows eosinophil and mast-cell depleting activity. By reducing the number of 


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blood and tissue eosinophils and reducing the number of tissue mast cells and/or blocking 
degranulation and induction of mast-cell derived mediators, AK002 may be useful in the 
treatment of patients with chronic urticaria. 
2.7 
Overview of Animal Studies with AK002 
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 (MCs), eosinophils, and basophils. In single- and repeat-dose 
studies in Siglec-8 transgenic mice, AK002 demonstrated selective depletion of peritoneal MCs 
and circulating and tissue (spleen) eosinophils and basophils. AK002 was well tolerated in single 
and repeat-dose pharmacology studies. 
In 2 Good Laboratory Practice (GLP) toxicity studies, Siglec-8 transgenic mice received weekly 
intravenous (IV) doses of AK002 weekly for 4 weeks (5 total doses) or 6 months at 2 dose 
levels, 50 mg/kg and 100 mg/kg. The high dose, 100 mg/kg, was selected to represent a dose 
10-fold higher than the highest proposed clinical dose, 10 mg/kg. Consistent with its mechanism 
of action, AK002 decreased eosinophils at both doses. There were no adverse AK002-related 
effects on survival, body weights, clinical observations, clinical pathology, or anatomic 
pathology at either dose. The no-observed-adverse-effect level (NOAEL) following repeat IV 
administration of AK002 to transgenic mice was 100 mg/kg. 
2.8 
Overview of Prior Clinical Studies with AK002 
AK002 has been studied in two Phase 1 studies: one ongoing clinical trial in Germany 
(AK002-001) in patients with indolent systemic mastocytosis (ISM) and one completed Phase 1 
clinical trial in healthy volunteers in Australia (AK002-002). 
• 
Study AK002-001, A Phase 1, Single Ascending Dose and Multiple Dose Study to Evaluate 
the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AK002 in Patients 
with Indolent Systemic Mastocytosis, is in progress in patients with ISM. Up to 30 patients 
will receive AK002: single IV infusion in 6 single-patient cohorts at 0.0003 mg/kg, 
0.001 mg/kg, 0.003 mg/kg, 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg; single IV infusion in two 
3-patient cohorts at 0.3 mg/kg and 1 mg/kg; and up to 6 patients in a cohort with up to 
6 infusions of 1 mg/kg every 28 days. In addition, two subjects have received a dosing 
regimen of 1 mg/kg, followed by 3 mg/kg for another 2 infusions. In the single-dose cohorts, 
all of which have been completed, AK002 has been generally well tolerated. Mild infusion-
relate reactions (IRRs) (nausea, vomiting, abdominal pain, flushing, dyspnea, headache, or 
hypertension) have been observed. Temporal interruption of the AK002 infusion and 
minimal intervention have resulted in prompt resolution of symptoms and ability to 


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complete the infusion without further complications. In patients with ISM receiving doses of 
0.1–3 mg/kg, objective measures of skin reactivity on stimulation (Darier’s sign) have 
improved, and 
 patients have reported substantial improvements in symptoms 
including resolution of diarrhea, reductions in pruritus, skin flushing or urticarial rashes, as 
well as qualitative improvements in abdominal pain and fatigue. 
• 
Study AK002-002, A Phase 1, Double-Blind, Placebo-Controlled, Single Ascending Dose 
and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of AK002 in Healthy Participants, compared AK002 with placebo in 
healthy volunteers, has completed enrollment and follow-up. In total, 51 subjects were 
enrolled: 
 AK002-treated subjects and 
 placebo-treated subjects. Subjects received a 
single IV infusion in one 4-subject cohort at 0.001 mg/kg (all subjects received AK002), 
single IV infusion in six 6-subject cohorts at 0.003 mg/kg, 0.01 mg/kg, 0.03 mg/kg, and 
0.1 mg/kg; 0.3 mg/kg and 1 mg/kg (4 subjects received AK002 and 2 subjects received 
placebo in each cohort); 8 subjects in a cohort with 2 infusions of 0.3 mg/kg every 28 days 
(6 subjects received AK002 and 2 subjects received placebo); and 3 subjects in a cohort with 
2 infusions of 1 mg/kg every 28 days (2 subjects received AK002 and 1 subject received 
placebo). Among the 51 enrolled subjects, only 1 subject experienced a delayed IRR that 
was considered a serious adverse event (SAE): a 24-year old Caucasian woman developed 
nausea, emesis, chills, and rigors and felt pre-syncopal 3 hours after receiving a 1 mg/kg 
dose of AK002. She received promethazine, normal saline, hydrocortisone, and 
metoclopramide and was noted to have a decrease in blood pressure. She was treated with 
0.3 mg adrenaline IM, and blood pressure quickly stabilized. No further urgent treatment 
was required, and she recuperated without any sequelae. Mild IRRs comprising nasal 
congestion, headache, nausea, and throat and chest tightness have been observed. When 
reactions did occur during the infusion, temporal interruption of the AK002 infusion and 
minimal intervention resulted in prompt resolution of symptoms and ability to tolerate the 
infusion without further complications. Of note, in the multiple-dose cohort, subjects were 
able to tolerate the second study drug infusion better than the first study drug infusion. This 
observation is consistent with rates of IRRs observed with other monoclonal antibodies with 
ADCC activity. 
In both Phase 1 studies, AK002 at all doses was active at its target and caused rapid deletion of 
eosinophils, consistent with its mechanism of action. The duration of eosinophil depletion 
corresponded with the detection of AK002 in the blood. 


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3. 
Study Design 
This is an exploratory, proof-of-concept, open-label pilot study to assess the effects and safety of 
AK002 in subjects with CU refractory to standard treatment (single-dose antihistamine 
treatment). 
This design is intended to assess the effects and safety of AK002 in subjects with CU refractory 
to standard treatment. Following this study, if this indication is pursued, a randomized double-
blind placebo-controlled study will be considered. 
4. 
Objectives 
4.1 
Primary Objective 
To assess the efficacy of AK002 on symptoms in subjects with CU (change in urticaria control 
test; UCT score) 
4.2 
Secondary Objectives 
The effect of AK002 on urticaria symptoms, QOL, provocation testing, and histological criteria 
The efficacy, safety and pharmacodynamics of AK002 in CU subjects will be assessed through 
the following evaluations: 
1) Safety and tolerability (adverse events, laboratory safety tests, etc.) 
2) Disease activity scores (UAS7, 
) 
3) 
 
4) Number of symptom-free days 
5) Use of rescue medication (up to 3 sgAH tablets/day) 
6) Effects on 
 
7) Number of 
 
8) 
 
9) Changes in trigger thresholds (in CINDU, including CholU) 
10) Rate of 
 (UCT, 
 
 
11) Serum levels of potential biomarkers of disease activity and treatment responses 
12) Rates of relapse and sustained response (during post-treatment follow-up period) 


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5. 
Endpoints 
5.1 
Primary Endpoint 
The primary endpoint is the change in Urticaria Control Test (UCT), a score for symptom control 
in chronic urticaria, from Day 1 (baseline) to Week 22 in CU subjects after treatment with 
AK002. At Baseline, a 4-week recall will be recorded, prior to first study drug administration. A 
change of the UCT score of 3 or more points is regarded as clinically relevant (minimal clinically 
important difference [MCID]). 
5.2 
Other Endpoints 
1) Safety of subjects treated with AK002: This includes physical examination, routine safety 
laboratory assessments, vital signs, electrocardiogram (ECG), urine safety, and adverse 
event reporting (Visits 2–10) 
2) Change in disease activity as assessed by UAS7 and/or 
 (from Baseline to 
Visits 3, 5, 8, and 10) 
3) Change in number of symptom-free days per week (patient diary-based CSU score; wheals, 
flares, itch, avoidance behavior) from Baseline to Visits 3, 5, 8, and 10 
4) Change in 
 assessed by 
 
 from Baseline to Visits 3, 5, 8, and 10 
5) Change in number of intake of rescue medication from Baseline to Visits 3, 5, 8, and 10 
6) In case of 
, change in 
 from Visit 2 to Visit 3, 5, 8, and 
10, as assessed by 
 
7) Change in number of 
 from Baseline to 
Visits 3, 5, 8, and 10 
8) Change in 
 from Baseline to Visits 3, 5, 8, and 10 
9) Changes in trigger threshold from Baseline to Visits 2, 3, 5, 8, and 10, as assessed by Pulse 
Controlled Ergometry Test (PCE) and FricTest®, as applicable 
10) Rates of complete response, partial response, and non-response based on UCT, 
, trigger thresholds (where applicable), and QoL from Baseline to Visits 3, 
5, 8, and 10 
11) Serum levels at baseline and change from Baseline to Visits 3, 5, 8, and 10 of serum levels 
of potential biomarkers in AK002-treated subjects (e.g., tryptase, eosinophils, total IgE, 
basophils, eosinophil cationic protein) 
12) Rates of AK002-treated subjects with relapse, rebound, sustained treatment effects at Visit 7 


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6. 
Investigational Plan 
6.1 
Study Design 
The study comprises a screening period of 4 weeks, with daily oral intake of standard-dose (once 
daily) second-generation AH (standard of care, with on-demand intake of up to 3 additional AH 
tablets per day). The treatment period comprises a daily oral intake of standard-dose second-
generation AH and AK002 administered by IV infusion at Days 1, 29, 57, 85, 113, and 141. 
Subjects will be followed for an additional 8 weeks, and at Weeks 22, 24, and 28 the primary and 
secondary objectives will be evaluated. 
It is expected that approximately 48 subjects will be enrolled and assigned to 3 cohorts: 
• 
Approximately 12 subjects with Cholinergic Urticaria (CholU) 
• 
Approximately 12 subjects with Urticaria Factitia (UF) 
• 
Approximately 12 XOLAIR® (omalizumab) naïve subjects with Chronic spontaneous 
urticaria (CSU) 
• 
Approximately 12 subjects with Chronic spontaneous urticaria (CSU) who did not achieve 
an adequate response to XOLAIR® (omalizumab) in the opinion of the Investigator 
The open-label design facilitates the assessment of efficacy, as well as safety in the cohort. 
Table 1 shows the study outline and Table 3 shows the schedule of assessments. 
Table 1 
Study Outline 
Screening 
Treatment 
Follow-up 
 
0.3 mg/kg 
1 mg/kg 
1 mg/kg 
3 mg/kg* 3 mg/kg* 
3 mg/kg* 
1 
2 
3 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Week -4 
Week 0 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 22 
Week 24 
Week 28 
Day -28 
Day 1 
Day 29 
Day 57 
Day 85 
Day 113 
Day 141 
Day 155 
Day 169 
Day 197 
* Increase to 3 mg/kg if UCT score is <12 and/or at the discretion of the Investigator in consultation with the 
Allakos Medical Monitor. If UCT score is ≥12, and if the Investigator in consultation with the Medical Monitor 
feels that the patient has experienced adequate symptom improvement, then continue with the 1 mg/kg dose. 
6.1.1 
Screening Period 
At the beginning of the screening period, eligible subjects will be asked to sign the informed 
consent form (ICF) and their current medication will be discussed. During the screening period, 
subjects will continue with their current antihistamine medication (approved dose). 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 ID number and re-screened once. Subjects re-screened within 


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30 days of signing the initial consent will not need to sign a new ICF providing there have been 
no changes to the ICF. A patient is considered enrolled in the trial when the patient receives their 
first dose of AK002. 
6.1.2 
Treatment Period 
During the Treatment Period, all eligible subjects will receive AK002 by IV infusion every 28 
days. The first dose will be administered at the beginning of the treatment period Day 1 (Visit 2) 
after baseline measurements. At Day 141 (±2 days) (Visit 7), the final dose of AK002 will be 
given. Throughout the treatment period, subjects must maintain stable doses of their baseline AH 
dose and treatment regimen and remain on a stable treatment regimen through the end of the 
study. Patient’s use of rescue medication will be monitored and reviewed throughout the 
treatment period and if necessary adjusted according to the current urticaria guidelines 
(Zuberbier, 2014). Subjects are expected to attend all site visits based on the assessment schedule 
(see Table 3). 
6.1.3 
Follow-Up Period 
After completion of the Treatment Period, all subjects enter an 8-week follow-up period to 
obtain further information on the impact of AK002 treatment on urticaria activity and relapse of 
symptoms. No investigational treatment will be given during the post-treatment Follow-up 
Period; however, subjects are allowed to take their rescue medication. Rescue medication (a non-
sedating antihistamine) will be provided and used on an as-needed basis during the post-
treatment Follow-up Period. 
6.1.4 
Extended Dosing (Optional)  
Subjects in the CholU, UF, and CSU-XOLAIR® (omalizumab) failure cohorts who received all 
6 infusions of AK002, were followed through at least through Day 155, and demonstrated severe 
recurring symptoms of urticaria following discontinuation of treatment (as defined below) will 
be eligible to receive extended dosing with up to 12 additional doses of AK002 (see 
Appendix 2).  
To qualify for extended dosing, subjects must have a baseline (Day 1) UCT of ≤5 and a week 22 
(Day 155) UCT of ≥12 (Complete Response). They must have a UCT of ≤5 recorded between 
Day 155 and Day 309 (i.e., within 6 months from last dose). 
6.2 
Rationale for the Study Design 
This exploratory clinical trial is designed to evaluate the efficacy and safety of AK002 in 
subjects with chronic urticaria. AK002 is a novel monoclonal antibody that inhibits Siglec-8, 
expressed on mast cells, eosinophils, and to a lesser degree, on basophils. Considering that CU is 


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regarded as mast cell-driven disease, it is reasonable to assume that AK002 could be beneficial in 
CU. 
The gold standard treatment of CU comprises administration of antihistamines. In severe cases, 
antihistamines can be increased up to 4 times the standard dose. But there remains a significant 
proportion of subjects with CU that is not sufficiently controlled despite high doses of 
antihistamines, displaying a clear unmet medical need (Koch, 2016). CINDU subjects have no 
other treatment option. Therefore, there is an unmet need for new targeted therapeutic options for 
subjects with CSU and CINDU. This study will provide valuable insights into the therapeutic 
potential of AK002 in improving quality of life in these subjects, in addition to reducing CU 
symptoms. 
This design is intended to assess the effects and safety of AK002 in subjects with CU refractory 
to standard treatment. Following this study, if this indication is pursued, a randomized double-
blind placebo-controlled study will be considered.  
6.3 
Rationale for the Dose/Regimen, Route of Administration, and Duration 
of Treatment 
6.3.1 
Rationale for AK002 Dose and Regimen 
The proposed AK002 dose of 0.3 mg/kg administered at Day 1 and increased to 1 mg/kg at 
Day 29, Day 57, and subsequently to 3 mg/kg on Days 85, 113, and 141 is based on prior 
experience with AK002 in healthy volunteers and in subjects with ISM. Also, the long-term 
continuation treatment will provide the option of an additional 12 months of treatment for 
patients with severe disease at baseline who recorded a complete response while on treatment 
with AK002 (1 mg/kg or 3 mg/kg) and who developed severe symptoms within 6 months of 
discontinuing AK002. The continuation protocol will be limited to patients who have no other 
treatment options, that is CholU, UF, or Xolair failures in patients with CSU.  
Subjects with ISM receiving 0.3 mg/kg, 1 mg/kg, and 3 mg/kg AK002 have reported 
improvement of their clinical symptoms in a dose-dependent fashion. For example, some ISM 
patients who showed some response to 1 mg/kg, showed improved symptom control when the 
dose was increased to 3 mg/kg. In general, AK002 was well tolerated in these subjects. A dose of 
0.3 mg/kg resulted in suppression of eosinophils for approximately 1 month, which would justify 
a monthly dosing regimen. In addition, a starting dose of 0.3 mg/kg has demonstrated an 
adequate safety and tolerability profile in previous and current clinical trials.  


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6.3.2 
Rationale for Concomitant Antihistamine Dose and Regimen 
The target population for this study comprises CU subjects who remain symptomatic despite 
treatment with AH therapy alone (at approved doses). The updated International Guideline on 
definition, classification, diagnosis, and management of urticaria (Zuberbier, 2014), evidence-
based recommendations by an international expert team, has led to a treatment algorithm that 
recommends as Step 1 and Step 2 the use of non-sedating AHs at approved, or increased doses 
(up to 4-fold), respectively. As Step 3, the addition of omalizumab, cyclosporin A, or 
montelukast (LTRA) is recommended. None of the therapeutic recommendations of Step 2–3 are 
currently licensed for subjects with CINDU, including CholU and UF; therefore, to reflect the 
most current treatment algorithm for CINDU subjects, this study allows use of AH (at approved 
doses) as background medication. 
6.4 
Risks and Benefits 
The inclusion and exclusion criteria are selected to enroll subjects with CU most likely to benefit 
from participating in the study. The overall risk will be minimized by compliance with the 
inclusion/exclusion criteria, close clinical monitoring including the use of a diary to monitor 
symptoms, and the use of rescue medication. See the Investigator Brochure for the complete 
safety summary of AK002. 
The long-term continuation treatment will provide the option of an additional 12 months of 
treatment for patients with severe disease at baseline who recorded a complete response while on 
treatment with AK002 (1 mg/kg or 3 mg/kg) and who developed severe symptoms within 
6 months of discontinuing AK002. The continuation protocol will be limited to patients who 
have no other treatment options, that is CholU, UF, or Xolair failures in patients with CSU.  
The Investigator will provide the patient with written instructions to contact them if symptoms of 
CU worsen. Investigators will be instructed on acceptable treatments for worsening CU, which 
will allow subjects to continue on the study. The clinical benefits and safety profile of AK002 in 
subjects with CU has not yet been established. The risk for subjects participating in this study 
includes the potential for known safety issues, such as hypersensitivity reactions including 
anaphylaxis (Appendix 1), as well as for any unknown safety effects that could occur. 
7. 
Population 
The study population will be comprised of approximately 48 adult subjects (≥18 and ≤85 years 
old) with the diagnosis of CU. Approximately 12 subjects of each subgroup of CU (CholU, UF, 
CSU-XOLAIR® (omalizumab) naïve, CSU-XOLAIR® (omalizumab) failures) will be recruited. 
Subjects with acute urticaria will be excluded. 


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Approximately 48 subjects enrolled at approximately 4 study centers in the USA and Germany 
are expected to participate in the study. 
7.1 
Rationale for the Number of Subjects 
The planned sample size of approximately 48 subjects is based on common practice in early 
phase, proof-of-concept studies. 
7.2 
Inclusion/Exclusion Criteria 
The Investigator must ensure that all subjects meet the following inclusion criteria and none of 
the exclusion criteria. 
7.2.1 
Inclusion Criteria 
1) Adults (≥18 and ≤85 years old) 
2) Body weight <125 Kg 
3) Informed consent signed and dated 
4) Able to read, understand, and willing to sign the informed consent form and comply with 
study procedures 
5) Diagnosis of CU for at least three months, refractory to antihistamine treatment in single or 
4-fold dosage 
6) Willing, committed, and able to return for all clinic visits and complete all study-related 
procedures, including willingness to have IV infusion of study drug administered by a 
qualified person 
7) Females of childbearing potential must have a negative pregnancy test at Baseline. Female 
subjects must be willing to use highly effective contraception (Pearl-4 Index <1) or abstain 
from sexual activity from Screening until the end of the study, or for 120 days following the 
last dose of study drug, whichever is longer. A woman will be considered not of 
childbearing potential if she is post-menopausal for greater than two years (FSH >40 mL) or 
surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). 
 
Male patients with female partners of childbearing potential must agree to use a highly 
effective method of contraception from Screening until the end of the study or for 120 days 
following the last dose of study drug, whichever is longer. All fertile men with female 
partners of childbearing potential should be instructed to contact the Investigator 
immediately if they suspect their partner might be pregnant (e.g., missed or late menstrual 
period) at any time during study participation. 


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8) No participation in other clinical trials 4 weeks before participation in this study 
9) Uncontrolled CU (UCT <12) at the time of enrollment 
10) For extended dosing, subjects must have a baseline (Day 1) UCT of ≤5 and a week 22 
(Day 155) UCT of ≥12 (Complete Response). They must have a UCT of ≤5 between 
Day 155 and Day 309 (i.e., within 6 months from last dose). 
7.2.2 
Exclusion Criteria 
1) Acute urticaria 
2) Concurrent/ongoing treatment with immunosuppressives (e.g., cyclosporine, methotrexate, 
dapsone, or others) within 4 weeks or 5 half-lives prior to Baseline, whichever is longer 
3) Significant medical condition rendering the patient immunocompromised or not suitable for 
a clinical trial 
4) Significant concomitant illness that would adversely affect the subject’s participation or 
evaluation in this study 
5) History of malignancies within five years prior to screening other than a successfully treated 
non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cancer 
6) Presence of clinically significant laboratory abnormalities 
7) Lactating women or pregnant women 
8) Substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) 
within the last 5 years that could limit the subject’s ability to comply with study procedures 
9) Subjects who are detained officially or legally to an official institute or those that have been 
committed to an institution by virtue of an order issued either by the judicial or the 
administrative authorities will be excluded 
10) Use of omalizumab within the last 2 months 
11) Receipt of intravenous IgG therapy 30 days prior to Baseline 
12) Plasmapheresis 30 days prior to Baseline 
13) Use (daily or every other day) of Doxepin 14 days prior to Baseline 
14) Receipt of inactive vaccination or live attenuated vaccine 30 days prior to Baseline 
15) Use of H2-antihistamines 7 days before Baseline 


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16) Intake of leukotriene antagonists within 7 days prior to enrollment 
17) Intake of systemic corticosteroids (e.g., oral or depot) within 14 days prior to enrollment 
18) Positive screening for ova and parasite test at Baseline 
19) Treatment of helminthic parasite within 6 months of screening 
20) Positive HIV serology at screening 
21) Positive Hepatitis serology at baseline, except for vaccinated patients or patients with past 
but resolved hepatitis at screening 
22) Donation or loss of >500 mL of blood within 56 days prior to administration of study drug 
or donation of plasma within 7 days prior to administration of drug 
23) Known hypersensitivity to any ingredients of AK002 or drugs related to AK002 (e.g., 
monoclonal antibodies, polyclonal gammaglobulin) 
8. 
Study Treatment 
8.1 
Investigational Treatment 
AK002 will be administered as an intravenous (IV) infusion at a dose of 0.3 mg/kg given over a 
period of approximately 4 hours on Study Day 1. If well tolerated, dose will be increased to 
1 mg/kg, given over a period of approximately 4 hours on study Day 29 and Day 57 (±2 days). 
Dose will be increased to 3 mg/kg on Days 85, 113, and 141 (±2 days) if the UCT score is <12 
and/ or at the discretion of the Investigator in consultation with the Allakos Medical Monitor. If 
the UCT score ≥12, and if the Investigator in consultation with the medical monitor feels that the 
patient has received adequate symptom improvement, patient will remain at the 1 mg/kg dose. 
All doses will be given over a period of approximately 4 hours. The duration of infusion and the 
rate at which the infusion is given may be adjusted based on Investigator discretion.  
The amount of AK002 to be administered will be calculated based on the patient’s body weight 
determined within 24 hours of each infusion. 
8.2 
Concomitant Treatment 
One hour prior to dosing with AK002, subjects will receive pre-treatment oral doses of 
acetaminophen/paracetamol (1000 mg) and cetirizine (10 mg) for doses 1 and 2. Any 
premedication for subsequent doses will be based on the Investigator’s discretion. 


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Subjects will be treated with a standard dose of second-generation AH (once per day) or up to a 
4-fold dose of second-generation AH (standard of care) with dose and regimen established 
during Screening. In the event of symptom resolution during the study, the dose and schedule of 
AH treatment established during screening must be continued throughout the study. 
8.3 
Treating the Patient 
8.3.1 
Patient Numbering 
Each patient will be assigned a Patient ID Number (PID) by the site after the patient provides 
written informed consent. Each patient is uniquely identified in the study by a combination of the 
study number, site number and the patient’s disease code. 
• 
The first 3 digits will designate the study number, as assigned by Allakos (206 for this 
study). 
• 
The next 3 digits will designate the site number, as assigned by Allakos. 
• 
The last 3 digits will designate the disease code and order of consent at the site. 
– Disease codes are as follows: 1 = CholU, 2 = UF, 3 = CSU (Xolair Naïve), and 4 = CSU 
(Xolair Failure) 
– The first patient consented at each site will be assigned their disease code + “01”, and 
subsequent subjects will be assigned consecutive numbers based on consent order at the 
site (e.g., the second patient consented at the site will be assigned their disease 
code + “02”, and the third patient consented at the site will be assigned their disease 
code + “03”, etc.) 
 
Example: For example, Site 003 consented 4 patients. The first patient has CSU (Xolair 
Naïve), the second patient has UF, the third patient has CholU, and the fourth patient has 
CSU (Xolair Failure). The first patient will be assigned PID 206-003-301, the second patient 
assigned PID 206-003-202, the third patient assigned PID 206-003-103, and the fourth 
patient assigned PID 206-003-404. 
Once assigned to a patient, a PID number will not be reused. The patient will maintain the same 
PID number throughout the entire study except if the patient fails the first screening. If a patient 
signs the ICF but does not meet the inclusion/exclusion criteria, the patient will be considered a 
screen failure. The patient can be re-screened one additional time during the clinical trial. 
However, if this occurs the site will assign the patient a new PID at the subsequent screening 
visit. If the ICF has been signed within 30 days and there are no new revisions, a new ICF is not 
necessary. 


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8.3.2 
Formulation of AK002 
AK002 is a humanized non-fucosylated IgG1 monoclonal antibody directed against Siglec-8. 
AK002 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 AK002 formulation is 
 (use 
 for 
dose prep) AK002 in 
 
 pH 6.0, in sterile water for injection. 
Allakos, Inc. will supply the investigational site with AK002. AK002 must not be shaken or 
frozen. AK002 will be stored by the study site at 2–8ºC under lock, pending drug preparation. 
Access will be restricted to designated study pharmacy staff. All clinical supplies will be 
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 Principal 
Investigator and captured as a deviation. 
The NaCl 0.9% for IV injection is commercially available and will be ordered as needed. The 
NaCl 0.9% should be stored at room temperature. 
Study drug will be administered by IV infusion using an infusion pump. Dose preparation and 
administration details are included in the study Pharmacy Manual. 
8.3.3 
Supply of AK002 to the Investigational Site 
The Sponsor (or designee) will ship study drug to the investigational sites. The initial study drug 
shipment will be shipped after site activation (i.e., after all required regulatory documentation 
has been received by the Sponsor and a contract has been executed). Subsequent study drug 
shipments will be made by the Sponsor or designee. 
Each vial will be labeled with the required investigational use statement, lot number, and 
directions for storage. 
8.3.4 
Preparation of Study Drug 
Please refer to the Pharmacy Manual for additional details regarding study drug preparation. 
The amount of AK002 to be administered will be calculated based on the patient’s body weight 
determined within 24 hours of each infusion. 
The calculated amount of study drug based on body weight will be diluted with 0.9% NaCl for 
IV injection. 
The final combined volume of the IV bag of study drug + 0.9% NaCl will be 120 mL. 


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Note: 
Exactly 100 mL of the calculated dose of study drug will be administered to the patient. 
The extra 20 mL is to be used to prime the IV infusion line during the preparation of the 
IV line at the bed side. 
It is recommended that each dose of 120 mL is prepared in an empty medication delivery bag. 
For all 6 doses (0.3 mg/kg on Day 1, 1 mg/kg on Day 29 and Day 57, and 3 mg/kg on Day 85, 
Day 113, and Day 141), 100 mL dose of study drug will be infused over approximately 4 hours.  
After each dose, the patient will be monitored for at least 4 hours after IV administration. At the 
discretion of the PI, monitoring may be extended for an additional 24 hours. 
Detailed instructions for preparing the drug are in the Pharmacy Manual. 
8.3.5 
AK002 Administration 
Premedication with oral doses of acetaminophen/paracetamol (1000 mg) and cetirizine (10 mg) 
will be given 1 hour prior to the infusion for doses 1 and 2. Any premedication for subsequent 
doses will be based on the Investigator’s discretion. AK002 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. 
Based on the patient’s weight, the designated clinical staff will prepare the appropriate dilution 
of AK002 at 0.3 mg/kg (for Day 1), 1 mg/kg (for Day 29 and Day 57), and 3 mg/kg (for Day 85, 
Day 113, and Day 141) for IV administration. Appropriate aseptic technique will be used, and 
the study drug will be prepared according to the Pharmacy Manual for AK002. 
The site’s designated clinical staff will keep accurate and current accounting of the preparation 
and dose calculation of study drug for each patient, with source, quantities of study medication 
dispensed, used, and returned. All dosage calculations will be documented on the source 
documents. A study drug receipt, dispensation, and disposition log will be maintained by the 
pharmacist on the Investigational Drug Accountability Record. A study monitor will verify 
entries on these documents throughout the course of the study. 
Specific instructions on administration are detailed in the Pharmacy Manual. In general, all doses 
i.e., 0.3 mg/ kg at Day 1, 1 mg/kg at Day 29 and Day 57, and either 1 mg/kg or 3 mg/kg 
(depending on UCT score) at Day 85, Day 113, and Day 141 will be given as an IV infusion over 
approximately 4 hours, following an observation period of 4 hours. 
All dosages prescribed and dispensed to the patient and all dose changes during the study must 
be recorded on the appropriate eCRF. 


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Subjects in the CholU, UF, and CSU-XOLAIR® (omalizumab) failure cohorts who received all 
6 infusions of AK002, were followed through Day 155, and demonstrated severe symptoms of 
urticaria following discontinuation of treatment will be eligible to receive extended dosing with 
up to 12 additional doses of AK002 (see Appendix 2).  
For extended dosing, subjects must have a baseline (Day 1) UCT of ≤5 and a week 22 (Day 155) 
UCT of ≥12 (Complete Response). They must have a UCT of ≤5 between Day 155 and Day 309 
(i.e., within 6 months from last dose). 
All subjects that decide to receive extended dosing will start with a dose of 0.3 mg/kg, followed 
by possible dose increases to 1 mg/kg and 3 mg/kg for subsequent infusions. 
The Investigator in consultation with the Medical Monitor may increase the dose to 6 mg/kg and 
then to 10 mg/kg if they think that the patient has not received benefit from the lower doses. 
8.3.6 
Permitted Study Drug Dose Adjustments and Interruptions 
AK002 dose adjustments are not permitted. The IV infusion may be interrupted, and/or the rate 
may be reduced by 50%, if a patient experiences an infusion-related reaction. The time the 
infusion is initiated/concluded (including any interruptions) will be documented in the eCRF. 
Infusion interruptions and infusion rate reductions should be documented when reporting any 
infusion-related reaction AEs. If dose is restarted after an interruption, the infusion must be 
completed within the 8-hour stability window. Administration will be discontinued if, in the 
opinion of the Investigator, an interrupted infusion cannot be restarted for safety reasons or if the 
infusion cannot be completed within the 8-hour stability window.  
Administration will also be discontinued in any patient experiencing an SAE during the course of 
the infusion. A lower infusion rate in new subjects will be considered after assessment of safety 
results and discussion with the Medical Monitor. 
Acetaminophen, antihistamines, and, if needed, a glucocorticoid (e.g., 125 mg 
methylprednisolone IV) may be administered to the patient if the patient experiences reactions 
that are considered mild to moderate (e.g., itching or a localized rash) at the Investigator’s 
discretion. If a patient experiences signs or symptoms of anaphylaxis, the patient will be treated 
with standard of care, such as diphenhydramine, acetaminophen, methylprednisolone, 
epinephrine, and other supportive measures along with cessation of the infusion. As part of the 
anaphylaxis assessment, a sample of blood should be obtained for plasma histamine and tryptase 
level within 1 to 2 hours of the onset of the symptoms. 


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Any missed or altered study drug administrations must be recorded on the Dosage 
Administration Record eCRF in order to reconstruct an accurate dosing history for each patient. 
8.3.7 
AK002 Accountability 
The site’s designated pharmacist will keep accurate and current accounting of the preparation 
and dose calculation of study drug for each patient, with source, quantities of study medication 
dispensed, used, and returned. All dosage calculations will be documented in the source 
documents. A study drug receipt, dispensing, and disposition log will be maintained by the 
pharmacist on the Investigational Drug Accountability Record. A study monitor will verify 
entries on these documents throughout the course of the study. 
Used study drug vials must be inspected by the study monitor prior to destruction or return to the 
study drug vendor. 
8.3.8 
Measures of Treatment Compliance 
AK002 will be administered under supervision of the Principal Investigator or Sub-Investigator. 
The calendar date and 24-hour clock times when the infusion is initiated and concluded, 
including any interruptions, will be documented in the eCRF. 
8.3.9 
Dietary and Lifestyle Restrictions 
Subjects will refrain from alcohol and strenuous exercise (e.g., heavy lifting, weight training, 
aerobics) for at least 24 hours prior to each blood collection for clinical laboratory tests. Subjects 
will fast for at least 8 hours before blood for clinical laboratory tests is obtained. 
8.3.10 
Prohibited Treatments 
Use of the class of treatments displayed in Table 2 is NOT allowed after start of screening 
(Visit 1). The minimum required period without prohibited treatment before Visit 2 is also listed 
in Table 2. 


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Table 2 
Prohibited Treatments 
Medication 
Minimum Required Period 
without Medications 
Omalizumab 
within 2 months of Baseline 
H2-antihistamines 
7 days prior to Baseline 
Routine (daily or every other day during 5 or more consecutive 
days) doses of systemic corticosteroids 
14 days prior to Baseline 
Routine (daily or every other day during 5 or more consecutive 
days) doses of systemic hydroxychloroquine 
30 days prior to Baseline 
Routine (daily or every other day during 5 or more consecutive 
days) doses of methotrexate, cyclosporine A, cyclophosphamide, 
tacrolimus and mycophenolate mofetil 
4 weeks or 5 half-lives prior to Baseline 
Intravenous immunoglobulin G 
30 days prior to Baseline 
Plasmapheresis 
30 days prior to Baseline 
Regular (daily or every other day) doxepin (oral) 
14 days prior to Baseline 
Inactive vaccination 
30 days prior to Baseline 
Live attenuated vaccine 
30 days prior to Baseline 
Leukotriene Antagonists 
7 days 
If the prohibited treatment was used during the study for any indication, the patient must 
discontinue use of the prohibited treatment if he/she wishes to continue in the study. If the 
patient received a live virus vaccination during the study, the patient must discontinue study 
treatment. 
The list of prohibited medications is not considered all inclusive. Medication should be assessed 
for adherence to the indication and other inclusion/exclusion criteria. 
The Investigator should instruct the patient to notify the study site about any new medications 
he/she takes subsequent to receiving the study drug. All medications and significant non-drug 
therapies (including physical therapy and blood transfusions) administered following initial study 
drug treatment, must be listed on the concomitant medications/significant non-drug therapies 
CRF. 


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9. 
Discontinuation and Replacement of Subjects and Major Protocol Deviations 
9.1 
Definition of Early Termination from the Study 
A patient who discontinues the study before completing the Follow-Up visit at Week 28 is 
considered to have terminated early. All subjects who discontinue the study prior to completing 
the final Follow-Up visit should return to the site 28 (±2) days after the last dose of study drug or 
prior to this if necessary. If early termination occurs more than 28 days after the last dose of 
study drug, then perform the Early Termination Visit as soon as possible. 
9.2 
Definition of Study Completion 
A patient who completes visits through the end of the Follow-Up visit at Week 28 will be 
recorded as having completed the study. 
9.3 
Early Discontinuation of Study Drug 
A patient may be discontinued from study treatment at any time if the patient, the Investigator, or 
the Sponsor feels that it is not in the patient’s best interest to continue to participate in the study. 
The following is a list of possible reasons for study treatment discontinuation: 
• 
Patient withdrawal of consent 
• 
AE that, in the opinion of the Investigator, results in it being in the best interest of the 
patient to discontinue study treatment 
• 
Protocol deviation requiring discontinuation of study treatment 
If a patient is withdrawn from treatment due to an AE, the patient will be followed by the 
Investigator as noted in Section 9.4. 
All subjects who discontinue study treatment should return to the site 28 (±2) days after the last 
dose of study drug for procedures listed under Post-Treatment Follow-Up. 
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. 
Reasonable attempts will be made by the Investigator to provide reasons for patient withdrawals. 
The reason for the patient’s withdrawal from the study will be specified in the patient’s source 
documents. 


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9.4 
Withdrawal of Subjects from Study 
Participation of a patient will be discontinued in the event that: 
• 
An AE or SAE that, in the judgment of the Investigator, requires withdrawal due to its 
nature, severity, or required treatment, regardless of the causal relationship to treatment 
• 
Major protocol deviations as determined by the Medical Monitor, including significant 
non-compliance, or loss to follow-up 
• 
Occurrence of an exclusion criterion which is clinically relevant and affects the patient’s 
safety or integrity of the study data, if discontinuation is considered necessary by the 
Investigator and/or Medical Monitor 
• 
Serum transaminases (ALT and/or AST) >3 × ULN AND total bilirubin >2 × ULN 
(confirmed by repeat testing) without an alternative explanation 
• 
Elevation of ALT or AST >3 × ULN (confirmed by repeat testing) with the appearance or 
worsening of symptoms felt by the Investigator to be potentially related to hepatic 
inflammation, such as fatigue, nausea, vomiting, right upper quadrant pain or tenderness, 
fever, rash, or eosinophilia 
• 
Use of a non-permitted concomitant drugs and treatments, as defined in Section 8.3.10 as 
determined by the Medical Monitor. 
• 
Withdrawal of the patient’s consent 
• 
Participation in any other trial during the duration of this trial as determined by the Medical 
Monitor. 
• 
Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (e.g., infectious disease) illness 
• 
Lack of efficacy 
• 
Study terminated by sponsor 
• 
Discretion of the Investigator 
If a patient is withdrawn from treatment due to an AE, the patient will be followed and treated by 
the Investigator until resolved or stable. 
Reasonable attempts will be made by the Investigator to provide reasons for patient withdrawals. 
The reason for the patient’s withdrawal from the study will be specified in the patient’s source 
documents. 


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9.5 
Replacement of Subjects 
Subjects who do not meet all eligibility criteria at Screening, or who qualify at Screening but are 
not enrolled, may be assigned a PID number and rescreened once. Patient re-screened within 
30 days of signing the initial consent will not need to sign a new ICF providing there have been 
no changes to the ICF. 
Enrolled subjects who withdraw from the study may be replaced at discretion of the Investigator 
and consultation with the sponsor. 
9.6 
Termination of study 
The Medical Monitor in collaboration with the Investigators will review the safety data on an 
ongoing basis throughout the study and will on a continuous ongoing basis evaluate the risk-
benefit ratio. The monitoring will focus on emerging safety profile and if a positive or neutral 
risk-benefit ratio is not present, the study may be interrupted or terminated. If a patient 
experiences a Grade IV toxicity reaction (according to the CTCAE), an immediate reevaluation 
of the risk-benefit ratio will be performed. 
10. 
Visit Schedule and Assessments 
Table 3 shows the schedule of assessments by study visit. Subjects should be seen for all visits 
on the designated day or as close to it as possible. 
Subjects discontinuing the study drug before completing the 12-week treatment period, and those 
who prematurely withdraw from the study for any reason, should be scheduled for an early 
termination visit as soon as possible, at which time all of the assessments listed for the final visit 
will be performed. 
Subjects who discontinue AK002 treatment also should return for the final assessments. If they 
refuse to return or are unable to do so, every effort should be made to contact them or a 
knowledgeable informant by telephone to determine the use of rescue medication and to 
complete the 
. 
At a minimum, they will be contacted for safety evaluations during the 28 days following the last 
dose of AK002, including the final contact at the 28-day point. Documentation of attempts to 
contact the patient should be recorded in the patient record. 
All data obtained from the assessments listed in Table 3 and described in detail in the protocol 
must be supported in the patient’s source documentation.  
 


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Table 3 
Schedule of Assessments 
Description 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visits 5, 6, 7 
Visit 8 
Visit 9 
Visit 10 
Day -28 
 
Day 1 
 
Day 29 
(± 2) 
Day 57 
(± 2) 
Days 85, 113, 
and 141 (± 2) 
Day 155 
(± 2) 
Day 169 
(± 2) 
Day 197 
(± 2) 
Week -4 
Week 0 
Week 4 
Week 8 
Weeks 12, 16, 
and 20 
Week 22 
Week 24 
Week 28 
Screening 
Baseline/Dosing 
Dosing 
Dosing 
Dosingr 
Response 
Assessmentt 
Response 
Assessment 
End of Study/ 
Early Term. 
Informed consent 
xa 
 
 
 
 
 
 
 
Eligibility assessment/ 
confirmation 
x 
xb 
 
 
 
 
 
 
Demographic data 
x 
 
 
 
 
 
 
 
Medical history 
x 
 
 
 
 
 
 
 
Prior CU treatment 
x 
 
 
 
 
 
 
 
Prior/concomitant medication 
x 
x 
x 
x 
x 
x 
x 
x 
Rescue medication use 
 
x 
x 
x 
x 
x 
x 
x 
Study Drug administrationc 
 
x 
x 
x 
x 
 
 
 
Patient diaryd,s 
x 
x 
x 
x 
x 
x 
x 
x 
UAS7/
 
 
x 
x 
x 
x 
x 
x 
x 
 
 
 
x 
x 
x 
x 
x 
x 
x 
 
 
x 
x 
x 
x 
x 
x 
x 
UCT 
 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
x 
x 
x 
x 
x 
x 
x 
 
 
x 
x 
x 
x 
x 
x 
x 
Trigger threshold test (PCE and 
FricTest®)e 
x (if applicable) 
x (if applicable) 
x (if applicable) 
x (if applicable) 
x (if applicable) 
x (if applicable) 
x (if applicable) 
x (if applicable) 
Skin biopsyp 
 
x 
 
 
 
x 
 
 


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Table 3 
Schedule of Assessments cont. 
Description 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visits 5, 6, 7 
Visit 8 
Visit 9 
Visit 10 
Day -28 
 
Day 1 
 
Day 29 
(± 2) 
Day 57 
(± 2) 
Days 85, 113, 
and 141 (± 2) 
Day 155 
(± 2) 
Day 169 
(± 2) 
Day 197 
(± 2) 
Week -4 
Week 0 
Week 4 
Week 8 
Weeks 12, 16, 
and 20 
Week 22 
Week 24 
Week 28 
Screening 
Baseline/Dosing 
Dosing 
Dosing 
Dosingr 
Response 
Assessmentt 
Response 
Assessment 
End of Study/ 
Early Term. 
Anti-drug antibodiesf 
 
x 
x 
 
x 
x 
 
x 
PK analysisf 
 
x 
x 
 
x 
x 
 
x 
Blood safetyg 
x 
x 
x 
x 
x 
x 
x 
x 
Blood biomarkerso 
 
x 
x 
x 
x 
x 
x 
x 
Serologyh 
x 
 
 
 
 
 
 
 
Urinalysis 
xi 
x 
x 
x 
x 
x 
x 
x 
Urine pregnancy 
 
x 
x 
x 
x 
x 
x 
x 
Serum pregnancyj 
x 
 
 
 
 
 
 
 
Stool for ova and parasite 
x 
 
 
 
 
 
 
 
Physical examinations 
xk 
xl 
xl 
xl 
xl 
xl 
xl 
xl 
Vital signsm 
x 
x 
x 
x 
x 
x 
x 
x 
Weight 
x 
x 
x 
x 
x 
x 
x 
x 
12-lead ECGn 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events 
 
x 
x 
x 
x 
x 
x 
x 
Table 3 Notes 
a) 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 ID number and re-screened once. 
Subjects re-screened within 30 days of signing the initial consent will not need to sign a new ICF providing there have been no changes to the ICF. 
b) Baseline is defined as up to 48 hours prior to first dose. 
c) AK002 will be administered as a single peripheral IV infusion. Please refer to the Pharmacy Manual for detailed instructions on preparations, administration, and infusion rate. 
d) Subjects should complete the 
 on a weekly basis. On weeks where a clinic visit is not scheduled, the 
 should be completed at home.  


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Table 3 Notes cont. 
e) Subjects will be administered only the instruments that are relevant to their condition (see Table 4). FricTest will be assessed, if relevant, at every visit. The PCE can be 
performed at Visit 1 for diagnostic reasons and will be assessed at Visits 2 (at least 24 hours prior to dose), 8, and 10 only.  
f) 
ADA will be obtained Visits 2, 3, 5, 8 and 10. An unscheduled ADA blood sample may be obtained if an immunogenicity-related AE is suspected. PK will be analyzed 
retroactively using backup blood samples. 
g) Hematology, Chemistry and CBC with differential. 
h) Serology at Screening includes hepatitis B surface antigen (HBsAG), hepatitis C antibody, hepatitis B core antibody (anti-HBc), and human immunodeficiency virus (HIV). 
i) 
At Screening, include urine drug screening (alcohol, amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, 
methaqualone, opiates, phencyclidine) and urine cotinine tests. 
j) 
Blood for serum pregnancy tests at Screening Visit; blood for FSH is to be obtained only to confirm post-menopausal status. 
k) A complete PE will be performed by either the Investigator or designee as noted in Section 10.5.2. 
l) 
A symptom-directed PE, including assessments of possible infusion site reactions, will be performed by the Investigator or designee as needed. 
m) Vital signs, including supine systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate, will be taken after the patient has been in the supine position 
for ≥5 minutes and before any blood draw. On AK002 dosing days, vital signs will be measured pre-dose and at the end of infusion. 
n) 12 lead electrocardiograms (ECGs) must be recorded after 10 minutes rest in the supine position. 
o) Includes total IgE, absolute basophil and absolute blood eosinophil counts. Serum and plasma samples will be stored at -80°C for post hoc analysis of exploratory biomarkers. 
p) Skin biopsies are optional and will only be obtained the sites in Germany. 
q) 
 should be completed if the subject has a history of 
 at Screening. 
r) 
Dose may be increased to 3 mg/kg at Dose 4, 5, and 6 at Day 85, 113, and 141 respectively if the UCT is <12, and/ or at the discretion of the Investigator in consultation with 
the Allakos Medical Monitor, but will stay at 1 mg/kg if UCT is ≥12 and if the Investigator in consultation with the medical monitor feels that the patient has received 
adequate symptom improvement.  
s) 
During the physical exam the evaluating physician will also ask patients to rate the intensity of their atopic disease on a scale of 0–10; 0 (no symptoms) to 10 (worst possible 
symptoms). 
t) 
Subjects in the CholU, UF, and CSU-XOLAIR® (omalizumab) failure cohorts who received all 6 infusions of AK002, were followed through Day 155, and demonstrated 
severe symptoms of urticaria following discontinuation of treatment will be eligible to receive extended dosing with up to 12 additional doses of AK002 (see Appendix 2). For 
extended dosing, subjects must have a baseline (Day 1) UCT of ≤5 and a week 22 (Day 155) UCT of ≥12 (Complete Response). They must have a UCT of ≤5 between 
Day 155 and Day 309 (i.e., within 6 months from last dose). 
 


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10.1 
Information to be Collected on Screening Failures 
All subjects who have signed informed consent but not entered into the study will have the study 
phase completion page for the screening epoch, demographics, inclusion/exclusion, patient visit 
dates and serious adverse event (SAE) data collected. Adverse events that are not SAEs will be 
followed by the Investigator and collected only in the source data. 
10.2 
Patient Demographics/Other Baseline Characteristics 
Patient demographic and baseline characteristic data to be collected on all subjects include date 
of birth, age, sex, race, and ethnicity. Smoking habits will be evaluated. Relevant medical 
history/current medical condition present before signing the informed consent will be captured. 
Where possible, diagnoses, and not symptoms, will be recorded. Any history of atopic disease 
(dermatitis, rhinitis and asthma) will be collected. 
10.3 
Treatment Exposure and Compliance 
AK002 will be administered as an intravenous (IV) infusion at a dose of 0.3 mg/kg given over a 
period of approximately 4 hours on study Day 1. If well tolerated, dose will be increased to 
1 mg/ kg, given over a period of 4 hours on study Day 29 and Day 57 (±2 days). Dose will be 
increased to 3 mg/ kg on Days 85, 113 and 141 if the UCT score is <12 and/ or at the discretion 
of the Investigator in consultation with the Allakos Medical Monitor. If the UCT score is ≥12 
and if the Investigator in consultation with the medical monitor feels that the patient has received 
adequate symptom improvement, then the patient will continue to receive 1 mg/kg dose. 
The amount of AK002 to be administered will be calculated based on the patient’s body weight 
determined within 24 hours of each infusion.  
Administration of study drug should be recorded in the source documents and the corresponding 
eCRF for each administration. 
10.4 
Efficacy Assessments 
A number of cohort-specific efficacy variables will be assessed during the study. Several patient-
reported outcome (PRO) instruments are disease-specific, and subjects will be administered only 
the instruments that are relevant to their condition (Table 4). 


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Table 4 
PRO Instruments for Efficacy Assessment 
PRO Instrument 
CholU 
UF 
CSU 
Diary/Patients Diary Assessments (UPDD) 
x 
x 
x 
* 
x 
x 
x 
 
x 
x 
x 
* If applicable. All patients who have a history of 
 at Screening will complete the 
 
 and the 
 
10.4.1 
Urticaria Patient Daily Diary 
All subjects will be provided with an Urticaria Patient Daily Diary (UPDD). The subjects will 
receive clear instructions on the completion of the diary. UPDD includes CholUAS7 (itch, hives 
and elicitors) for CholU subjects or UAS7 (itch and hives) for UF and CSU subjects for clinical 
symptoms, and activity interference. Subinvestigators and subjects will receive appropriate 
training and guidance on the use of the Diary. 
10.4.2 
Urticaria Control Test 
The urticarial control test (UCT) is an instrument that is valid in all types of chronic urticaria, not 
only for CSU, and it can also be used in urticaria subjects suffering from recurrent angioedema. 
The UCT is a 4-item questionnaire for assessing CU disease activity retrospectively over the 
previous 4 weeks. Each item is rated on a Likert-type scale (0 = very often to 4 = not at all) and a 
total score is calculated (range, 0 to 16; higher scores indicate better disease control; scores ≥12 
are consistent with well-controlled disease. The higher the achieved score, the higher the level of 
disease control. 
UCT complete response is defined as a score of 16. Clinically relevant response is defined as 
improvement of 3 or more points in the UCT score (minimal clinically important difference 
[MCID]). The UCT total score will not be calculated when >1 item within the questionnaire is 
missing. 
10.4.3 
 
 is the first disease-specific 
 questionnaire for 
. It contains 
 each 
that are scored from 0 to 4 and relating to overall functioning (including work, physical, leisure 
and social activities), sleep, itching/embarrassment, mental status, swelling/eating, and limits 


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looks (limitations in choice of clothing or cosmetics used due to 
). The recall 
period is 2 weeks. Total scores range from 0 to 100, with higher scores indicating 
. 
 total score will not be calculated when >5 items within the questionnaire are 
missing. 
10.4.4 
 
 is a disease-specific 
 
questionnaire for 
. It consists of 
 items that can be grouped into domains. In 
addition to domain scores, it is possible to compute a total score. For score computation, the raw 
domain and raw total scores are transformed into percentage scores, indicating the location of the 
raw scores in relation (in percent) to its maximum possible score (linear transformation). 
Accordingly, the minimum and highest possible domain and total score are 0 and 100, 
respectively. 
10.4.5 
 
For subjects with 
, the 
 
 is the first disease-specific 
questionnaire for 
. It 
consists of 
 items. In addition to domain scores, it is possible to compute a total score. 
Accordingly, the minimum and highest possible domain and total score are 0 and 100, 
respectively. 
10.4.6 
 
 is the first specific 
 
questionnaire for all subjects that also have 
. It 
consists of 
 items that can be grouped into 2 domains. In addition to domain scores, it is 
possible to compute a total score. Accordingly, the minimum and highest possible domain and 
total score are 0 and 100, respectively. 
10.4.7 
 
 is a 
-specific health-related 
quality of life measure. Subjects rate their 
 symptoms as well as the impact of their 
 on various aspects of their lives. An overall score will be calculated as well as for 
the following domains: Symptoms and Feelings, Daily Activities, Leisure, Work and School, 
Personal Relationships, Treatment. The minimally important difference of the overall 
 
score for subjects with CSU has been estimated to be 
. 


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10.4.8 
  
 is the sum for 7 days of the daily 
 and the daily 
 
 multiplied by intensity of 
 The possible range of the weekly CholUAS7 score 
is 
. 
Complete 
 response is defined as 
=0 or by reduction of ≥90%. 
10.4.9 
 
 is the sum for 7 days of the daily 
 and the daily 
. 
The possible range of the weekly 
 score is 
. 
Complete 
 response is defined as 
 or by reduction of ≥90%. 
10.4.10 
 
 will be recorded by all subjects once daily in their Diary, on a scale of 
 (Table 5). A weekly 
 is derived by adding 
up the average daily scores of the 7 days preceding the visit. The possible range of the weekly 
score is therefore 
.  
A complete 
 response is defined as 
 = 0. 
Table 5 
 
10.4.11 Symptom-Free Days 
Symptoms will be recorded by the patient in their Diary. Symptom-free days (as defined in the 
SAP) per week or month can be calculated. 
10.4.12 Skin Biopsies 
Skin biopsies are optional and will be obtained at the sites in Germany.  
Two skin biopsies will be obtained: 
1) Visit 2 (Baseline, pre-dose), non-lesional skin 
2) Visit 8 (Week 22), non-lesional skin 


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Skin biopsies will be obtained using a 6-mm disposable punch pre-dose and post-dose as 
indicated above. Biopsy areas will be cleaned with an appropriate disinfectant, considering the 
nature of the patient’s skin. The skin will be numbed using an anesthetic injection. Each biopsy 
specimen will be immediately transferred into a 10 mL plastic tube containing approximately 4% 
neutral buffered formalin, pH 7.4. Hemostasis will be secured by pressure with gauze and 
suturing the wound. The sutured biopsy site will be covered by sterile patch. The biopsies will be 
embedded in paraffin and sectioned, and the tissue sections will be stained with monoclonal 
antibodies and analyzed by immunohistochemistry. Additional biopsy may be conducted in case 
of relapse of disease. 
The assessments of the skin biopsies will include: 
• 
Haematoxylin and eosin (H&E) and giemsa stains to assess the number of MCs and 
eosinophils in the skin 
• 
Other potential post hoc analyses to investigate the mechanism of action of AK002 
10.4.13 Laboratory Evaluations for Efficacy 
A venous blood sample is to be collected and sent to the laboratory at every treatment visit and 
during the follow-up period. The last blood sample will be collected on the last follow up visit. 
Samples will be assessed for total IgE, absolute basophil and eosinophil counts, and eosinophil 
cationic protein (ECP). 
A total of six 0.5 mL serum samples will be stored at -80°C at the study site for post hoc analysis 
of exploratory biomarkers. Two 0.5 mL plasma samples will be collected at Baseline and 
Week 22 and stored at -80°C at the study site for post hoc analysis. 
10.4.14 Trigger Threshold Tests (FricTest® and Pulse-Controlled Ergometry) 
A number of cohort-specific assessments will be used during the study. Instruments are disease-
specific and subjects will be administered only the instruments that are relevant to their 
condition. 
• 
The FricTest® will be used for diagnosing patients with symptomatic UF and for measuring 
their trigger thresholds and disease activity. 
• 
Pulse-controlled ergometry testing will be used to diagnose CholU and measure trigger 
thresholds. 
10.4.15 Measuring Disease Activity and Functional Status 
The following assessments will be administered to assess disease activity and functional status.  


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• 
The 
 will be used to determine disease activity in subjects 
with recurrent 
 independent of its underlying causes. Subjects will use the 
 
for 
 
 should be completed starting at Screening if the 
subject has a history of 
 at Screening. 
• 
The 
 and 
 scoring systems will be 
used to assess disease activity. 
10.5 
Safety Assessments 
10.5.1 
Medical Monitoring 
Dr. 
 should be contacted directly using the phone numbers and/or email 
address below to report medical concerns or for questions regarding safety. 
 
Allakos Medical Monitor  
 
, MD, PhD  
 
Phone: 
 
 
Email: 
 
10.5.2 
Physical Examination 
At screening (Visit 1) and other visits indicated on the Schedule of Assessments (Table 3), a 
complete physical examination will be obtained as follows: 
• 
General appearance 
• 
Respiratory 
• 
Hair and skin 
• 
Cardiovascular 
• 
Lymphatics 
• 
Abdomen 
• 
Head 
• 
Musculoskeletal 
• 
Eyes 
• 
Mental status 
• 
Ears, nose and throat 
• 
Thyroid 
• 
Neurological 
• 
Extremities 
In addition, the evaluating physician will also ask patients to rate the intensity of their atopic 
disease on a scale of 0–10; 0 (no symptoms) to 10 (worst possible symptoms). The patient’s 
atopic disease (dermatitis, rhinitis and/or asthma) will be determined and followed during the 
course of the study. 


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10.5.3 
Vital Signs 
Supine vital signs include blood pressure (BP) and pulse measurements. Systolic and diastolic 
blood pressure will be measured using a validated device with an appropriately sized cuff. In 
case the cuff sizes available are not large enough for the patient’s arm circumference, a 
sphygmomanometer with an appropriately sized cuff may be used.  
10.5.4 
Height and Weight 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram [kg] in indoor clothing, 
but without shoes) will be measured. 
10.5.5 
Laboratory Evaluations for Safety 
A venous blood sample is to be collected and sent to the central laboratory at every treatment 
visit. The last blood sample will be collected on the last follow-up visit. 
Note: 
In the case of an Infusion-Related Reaction (IRR), a 10 mL blood sample must be 
collected within approximately 2 hours from the onset of symptoms for exploratory 
analysis. 
10.5.6 
Hematology 
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential, and 
platelet count will be measured. Coagulation will be assessed by International Normalized Ratio 
(INR). 
10.5.7 
Clinical Chemistry 
Albumin, protein, glucose, total bilirubin, alkaline phosphatase, aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), total bilirubin#, direct bilirubin, gamma-
glutamyltransferase (GGT), albumin, creatinine kinase, chloride, calcium, sodium, potassium, 
magnesium, lactate dehydrogenase (LDH), creatinine, inorganic phosphorus, urea/BUN, uric 
acid, hs-CRP, fT3*, fT4* and total IgE will be measured. 
Notes: #If the total bilirubin concentration is increased above 1.5 times the upper limit of 
normal, direct and indirect reacting bilirubin should be differentiated. 
 
*fT3 and fT4 measured at Screening only. 
10.5.7.1 
Follicle-Stimulating Hormone 
A serum pregnancy test will be obtained at Screening (Visit 1) for all female subjects of 
childbearing potential. At Screening, follicle-stimulating hormone (FSH) will be tested on 
females to confirm post-menopausal status (FSH level >40 mIU/mL). 


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10.5.7.2 
Serology 
Blood will be obtained at Screening for serology tests, including hepatitis B surface antigen 
(HBsAG), hepatitis C antibody, hepatitis B core antibody (anti-HBc), and human 
immunodeficiency virus (HIV). 
10.5.7.3 
Anti-Drug-Antibodies  
Blood will be collected for determination of anti-drug antibodies (ADA) before the first dose at 
Day 1 (Visit 2), Day 29 (Visit 3), Day 85 (Visit 5), Day 155 (Visit 8), and Day 197 (Visit 10) at 
the study center. An unscheduled blood sample for ADA may be obtained if a related adverse 
event suspected of being associated with immunogenicity occurs. 
10.5.7.4 
PK Analysis 
PK will be analyzed retroactively if possible, using back up blood samples at the following 
timepoints- before the first dose at Day 1 (Visit 2), Day 29 (Visit 3), Day 85 (Visit 5), Day 155 
(Visit 8), and Day 197 (Visit 10)/End or Study/Early Termination). 
10.5.8 
Urinalysis 
A midstream urine sample (approximately 30 mL) will be obtained in order to avoid 
contamination with epithelial cells and sediments and allow proper assessments. 
Semi-quantitative “dipstick” evaluation for specific gravity, glucose, protein, bilirubin, ketones, 
leukocytes and blood will be performed at site. When a dipstick evaluation is abnormal, e.g., 
positive for WBC and/or blood, a urine sample needs to be sent to the lab for microscopic 
examination including RBC and WBC. Details on collection of urine for analysis are provided to 
Investigators in the Laboratory Manual. 
10.5.8.1 
Urine Drug Screen and Cotinine Test 
Urine samples will be collected at Screening for urine drug screening (alcohol, 
amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, 
cotinine, methadone, methaqualone, opiates, phencyclidine) and urine cotinine tests. 
10.5.9 
Fecal Collection 
Fecal collection kits will be provided to subjects during Screening for ova and parasite tests. 
Subjects will return the sample to the clinical site during the Screening period (Days -28 to -7). 
10.5.10 Electrocardiogram 
Standard 12 lead electrocardiograms (ECGs) must be recorded after 10 minutes rest in the supine 
position to ensure a stable baseline. The preferred sequence of cardiovascular data collection 
during study visits is: ECG collection first, followed by vital signs, and blood sampling. The 


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ECGs will be recorded at Visits 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. The print-outs will be generated 
and kept at the Investigator site as source documentation. Clinically significant ECG findings 
prior to dosing with AK002 must be reviewed by the Principal Investigator and/or cardiologist. 
Clinically significant abnormalities should be recorded on the relevant section of the Medical 
History/Current Medical Conditions/AE CRF page, as appropriate. 
10.5.11 Pregnancy Testing 
All women of childbearing potential will have a serum pregnancy test and urine pregnancy tests 
at the visits specified in Table 3. A positive urine pregnancy test requires immediate interruption 
of study medication until serum B-hCG is performed and found to be negative. If positive, the 
patient must be discontinued from the study. Urine pregnancy test kits will be provided to the 
sites by the Central Lab. 
To ensure patient safety, each pregnancy in a patient on study drug must be reported within 
24 hours of learning of its occurrence. The pregnancy should be followed up to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the presence or 
absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. Any SAE experienced during pregnancy must be reported on the SAE Report 
Form. 
10.5.12 Tolerability/Acceptability 
Other than adverse events, no specific tolerability/acceptability data are collected. 
10.6 
End of Trial 
End of trial is defined as last patient, last visit. 
11. 
Adverse Event Reporting 
All adverse events will be collected starting from the time of first AK002 infusion and until the 
end of the follow-up period or the Early Termination Visit, unless directed otherwise by Allakos. 
In accordance with 21 Code of Federal Regulation (CFR) 312.32(b) and International 
Conference on Harmonisation (ICH) Guidance E2A, an AE is any untoward medical occurrence 
in a clinical investigation of a patient 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 


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frequency in the current Investigator’s Brochure or of greater severity or frequency than 
expected based on the information in the Investigator’s Brochure. 
Events that do not meet the definition of an AE include: 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that leads to 
the procedure is an AE. 
• 
Situations where an untoward medical occurrence did not occur (e.g., social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected prior to first study drug infusion that do not worsen. 
• 
Significant reductions in numbers of eosinophils or basophils in blood count, as these are 
expected therapeutic effects of the study drug. 
11.1 
AE Recording 
At each evaluation, the Investigator or designee will determine whether any AEs have occurred. 
The assessment of an AE will be done pursuant to definitions set forth by ICH/Good Clinical 
Practice (GCP) guidelines and other applicable regulatory requirements. The patient will be 
questioned in a general manner and no specific symptoms will be suggested (e.g., ask the patient 
if he/she has had have had any “changes in health” since the last visit or assessment). 
Any initial information discovered by the Investigator or designee (i.e., complaint[s] and known 
start/end dates and times) will be documented. The Investigator or designee will assess the initial 
AE finding(s) to determine if the medical occurrence is in fact an AE by officially documenting 
the condition/diagnosis on the AE form. 
Action taken will be categorized as none, study drug permanently discontinued, dose modified, 
required concomitant medication, and/or other. 
Event outcome at resolution or time of last follow-up will be recorded as recovered, recovering, 
not recovered, recovered with sequelae, fatal, or unknown. 
11.2 
AE Severity 
AEs are to be recorded on the AE page of the eCRF. Severity will be graded according to the 
following definitions as listed in Table 6 as well as the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) Version 4.03. It should be pointed out that 
the term “severe” is a measure of intensity and that a severe AE is not necessarily serious. 


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When the intensity of an AE changes more than once a day, the maximum severity for the event 
should be listed. If the intensity changes over a number of days, these changes should be 
recorded separately (i.e., as having distinct onset dates). 
Table 6 
Adverse Event Severity Grading 
Grade 
Severity 
Description 
1 
Mild 
Transient or mild discomfort; no limitation in activity; no medical intervention or 
therapy required. The patient may be aware of the sign or symptom but tolerates it 
reasonably well. 
2 
Moderate 
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required. 
3 
Severe 
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible. 
4 
Life-threatening 
The patient is at risk of death due to the adverse experience as it occurred. This 
does not refer to an experience that hypothetically might have caused death if it 
were more severe. 
5 
Death 
Any adverse event where the outcome is death. 
11.3 
AE Relationship to Study Drug 
The relationship of an AE to the study drug should be assessed using the following the guidelines 
in Table 7. 
Table 7 
Adverse Event Relationship to Study Drug 
Relationship to 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). 
Possible 
The event cannot be explained by the patient’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 patient’s underlying medical condition, 
concomitant therapy, or other causes, and therefore, the Investigator believes no 
relationship exists between the event and study drug. 
11.4 
Adverse Events of Special Interest 
Selected non-serious and serious adverse events that meet criteria for classification as an 
Adverse Event of Special Interest (AESI) must be recorded in the eCRF, regardless of the 
Investigator’s assessment of relationship to the study drug. Beginning from the time of first study 
drug infusion and ending at Day 197 or the ET Visit (unless directed otherwise by Allakos), any 


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new AESI (or new information related to a previously reported AESI) must be recorded in the 
AE eCRF and designated as an “adverse event of special interest”. Information regarding date of 
event onset, event severity grading, action taken in response to event, investigator assessment of 
relationship to study drug, investigator assessment of seriousness, relevant laboratory, pathology, 
or radiology assessments, event outcome, and date of event resolution will be collected. The 
Medical Monitor will review data relating to safety during the study, including following the 
occurrence of AESIs to determine if specific action needs to be taken. The Medical Monitor may 
also request additional information (not described above) be provided. 
Adverse Events of Special Interest for this trial include:  
• 
Malignancies confirmed by histopathological report 
• 
Parasitic infections confirmed by positive clinical laboratory test 
• 
Opportunistic infections (infections known to be more severe or occur more frequently in 
immunosuppressed populations) as confirmed by positive clinical laboratory test 
• 
Infusion and hypersensitivity reactions, including anaphylaxis.  
An AESI that also qualifies as a SAE must also be reported as a SAE. AESIs that are also SAEs 
must be recorded in the AE eCRF and designated as both “serious” and as an “adverse event of 
special interest.” 
Note: 
If an IRR causes the infusion to be interrupted or slowed, a blood sample 
(approximately 5 mL serum and 5 mL plasma) must be collected within approximately 
1–2 hours from the onset of symptoms for Exploratory Safety Analysis.  
11.5 
Serious Adverse Events 
Serious adverse events will be recorded beginning with the signing of the informed consent form 
and ending at the end of the follow-up period or the Early Termination Visit unless directed 
otherwise by Allakos. SAE collection in the period after signing the informed consent and before 
the first study drug infusion will be limited to SAEs that are related to Screening activities. All 
SAEs will be collected starting at the time of the first infusion of study drug.  
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes: 
• 
Death 
• 
A life-threatening AE; the patient is 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. 


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• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant disability/incapacity 
• 
A congenital anomaly/birth defect 
Other important medical events may also be considered an SAE when, based on appropriate 
medical judgment, they jeopardize the patient or require intervention to prevent one of the 
outcomes listed. 
Note: 
Medical and scientific judgment should be exercised in deciding whether SAE reporting 
is also appropriate in situations other than those listed above. For example, important 
medical events may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the patient or may require intervention to prevent 
one of the outcomes listed in the definition above (including suspected transmission of 
an infectious agent by a medicinal product should be reported as an SAE). Any AE is 
considered an SAE if it is associated with clinical signs or symptoms judged by the 
Investigator to have a significant clinical impact. 
Inpatient hospitalization for the purpose of study drug infusion will not be reported as a serious 
adverse event in this trial. 
11.6 
Adverse Event Reporting Procedures 
11.6.1 
All Adverse Events 
Any clinically significant adverse event that is ongoing at the time of study completion or early 
termination will be followed by the investigator until event resolution, the adverse event is 
otherwise explained or not considered clinically significant by the investigator. 
Abnormal laboratory values or test results constitute adverse events only if they induce clinical 
signs or symptoms or require therapy. 
All AEs identified, whether serious or non-serious, will be recorded in the eCRF until Day 197 
or Early Termination. 
All AEs, regardless of seriousness, severity, or presumed relationship to investigational product, 
must be recorded using medical terminology in the source document and the eCRF. 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). The Investigator 
must record in the eCRF his or her opinions concerning the relationship of the AEs to the study 
drug. 


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Subjects (or their designees, if appropriate) must be provided with a “study card” indicating the 
name of the investigational product, the study number, the Investigator’s name, and a 24-hour 
emergency contact number, and excluded concomitant medications. 
11.6.2 
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 will report it immediately (within 24 hours of becoming aware of the 
SAE) by telephone, fax, or email to the Sponsor, Allakos, Inc. 
Serious adverse events must be reported to: 
 
, MD, PhD 
 
  
 
Phone: 
 
 
Fax: 
 
 
Email: SAE@allakos.com 
Serious adverse event report forms will be provided to the investigational site to assist in 
collecting, organizing, and reporting SAEs and follow-up information will be completed within 
24 hours. SAEs should also be recorded in EDC on the AE eCRF and designated as “serious.” 
The site will notify the Institutional Review Board (IRB)/ local authorities according to its 
guidelines. All SAE report forms will be completed within 24 hours. All efforts will be made to 
obtain accurate and complete medical records for the SAE. 
The patient’s condition will be followed by the Investigator or designated Sub-investigator until 
resolution of the condition or a return to baseline levels. If additional visits are required, the 
patient will be asked to return to the study site for further follow‐up. If condition is still ongoing 
at the time the patient exits the study, every effort will be made to continue to follow up with the 
patient for a reasonable period of time, 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 SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the patient’s participation in the study, must be followed until any of the 
following occurs: 


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• 
The event resolves 
• 
The event stabilizes 
• 
The event returns to baseline, if a baseline value is available 
• 
The event can be attributed to agents other than the investigational product or to factors 
unrelated to study conduct 
• 
It becomes unlikely that any additional information can be obtained (patient or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts) 
11.6.3 
Pregnancy Reporting 
Female subjects must be instructed to discontinue all study drugs and inform the Investigator 
immediately if they become pregnant during the study. 
The Investigator must report any pregnancy to Allakos, Inc. within 24 hours of becoming aware 
of it using the provided pregnancy reporting forms. The patient must be immediately 
discontinued from study drug. An uncomplicated pregnancy will not be considered an AE or 
SAE, but all pregnancies will be followed through term. 
Pregnancies are captured if they occur in female subjects or in the sexual partners of male 
subjects from the time the patient is first exposed to the study drug until 120 days after last dose 
received. 
Any congenital abnormalities noted at birth in the offspring of a patient 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. 
11.7 
Anaphylaxis 
Signs or symptoms of anaphylaxis will be carefully monitored and treated according to standard 
of care. In addition, as part of the anaphylaxis assessment, a sample of blood should be obtained 
for plasma histamine and tryptase level within 1 hour of the onset of the symptoms. Emergency 
crash cart equipment and medications, including multiple doses of epinephrine, pressors, 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 AEs of suspected anaphylaxis 
will be evaluated using the criteria specified in Appendix 1. 


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11.8 
Medical Monitoring 
Dr. 
 should be contacted directly using the phone numbers and/or email 
address below to report medical concerns or for questions regarding safety. 
 
Allakos Medical Monitor  
 
, MD, PhD 
 
Phone: 
 
 
Email: 
 
12. 
Data Review and Database Management 
12.1 
Site Monitoring 
The Investigator must maintain source documents for each patient in the study, consisting of case 
and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on eCRFs must be traceable to these source documents in the 
patient's file. Data not requiring a separate written record will be defined before study start and 
will be recorded directly on the eCRFs, which will be documented as being the source data. The 
Investigator must also keep the original informed consent form signed by the patient (a signed 
copy is given to the patient). 
The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the CRF entries. Monitoring standards require full verification for the presence 
of informed consent, adherence to the inclusion/exclusion criteria, documentation of SAEs, and 
the recording of data that will be used for all primary and safety variables. Additional checks of 
the consistency of the source data with the CRFs are performed according to the study-specific 
monitoring plan. No information in source documents about the identity of the subjects will be 
disclosed. 
12.2 
General Safety Monitoring 
The Investigators and Medical Monitor will review data relating to safety and to conduct of the 
study.  
The trial must be discontinued prematurely in the event of any of the following: 
• 
A life-threatening AE that is possibly or probably related to treatment 
• 
A fatal AE that is possibly or probably related to treatment 


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• 
New information leading to unfavorable risk-benefit judgment of the study drug, e.g., 
occurrence of significant previously unknown adverse reactions or unexpectedly high 
intensity or incidence of known adverse reactions, or other unfavorable safety findings 
• 
>50% of subjects at any time have been withdrawn due to drug-related AEs, including those 
related to abnormal laboratory results, or other safety findings 
• 
Sponsor’s decision that continuation of the trial is unjustifiable for medical or ethical 
reasons 
• 
Poor enrollment of subjects making completion of the trial within an acceptable time frame 
unlikely 
• 
Discontinuation of development of the Sponsor’s study drug 
Health Authorities and IECs will be informed about the discontinuation of the trial in accordance 
with applicable regulations. The trial may be terminated or suspended upon request of Health 
Authorities. 
13. 
Data Analysis 
This section outlines the statistical methods to be used for the analysis of the data from the study. 
A separate Statistical Analysis Plan (SAP), which will be completed and signed off prior to data 
base lock. 
When the SAP differs from analyses described in the protocol, the SAP will take precedence. 
Continuous variables will be summarized using number of non-missing observations, mean, 
standard deviation (SD), median, minimum, and maximum; categorical variables will be 
summarized using the frequency count and the percentage of subjects in each category. 
Baseline for data analysis is defined as the last assessment prior to the first infusion of the study 
drug. 
The primary summaries will be based on individual cohorts and the data from all 3 cohorts 
combined, wherever possible. 
13.1 
Populations for Analysis 
13.1.1 
MITT Population 
The modified intent-to-treat (MITT) population will consist of all subjects who are enrolled, 
have received at least one dose of study drug and have at least one post-baseline assessment of 
the primary efficacy variable UCT. 


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13.1.2 
Safety Population 
The safety population will consist of all subjects who are enrolled, have received at least one 
dose of study drug. 
13.1.3 
Per-Protocol Population 
The per-protocol (PP) population will consist of all subjects from the MITT-population for 
whom no major protocol violations adversely affecting the data interpretation are reported. 
13.2 
Disposition of Subjects 
The number of subjects who signed the informed consent, received a dose of study drug, 
completed, or discontinued from the study and the reason for study discontinuation will be 
tabulated. 
13.3 
Protocol Deviations 
Major protocol deviations will be summarized. Subjects with major protocol deviations affecting 
an efficacy evaluation will be excluded from the PP population. 
13.4 
Patient Demographics/Other Baseline Characteristics 
Descriptive statistics of subject characteristics and baseline values will be presented for all 
populations (total and by cohort). 
13.5 
Treatments (Study Drug, Concomitant Therapies, Compliance) 
Exposure to study drug will be summarized descriptively. The use of rescue medication is part of 
the efficacy assessment and will be reported there. Other concomitant therapy used both prior to 
and after start of study drug administration will be summarized. The WHO Drug Dictionary will 
be used for coding of medications. 
13.6 
Analysis of the Primary Objectives 
13.6.1 
Primary Efficacy Variable 
The primary variable is the change from baseline in UCT score. This variable will be 
summarized using descriptive statistics of mean, median, minimum, and maximum at Weeks 4, 
8, 12, 16, 20, 24, and 28. A 95% confidence interval for the mean will be computed. The 
summaries will be provided for all 3 cohorts combined as well as for each individual cohort. 


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Additionally, subjects achieving complete response (CR: defined as the total UCT score = 16) 
will be summarized with number and percent of subjects for each visit. Subjects achieving 0, 1, 
2, 3, and 4 CRs over the 7 post-baseline visits will also be summarized. Refer to the SAP for 
additional information. 
13.7 
Analysis of Secondary Objectives 
13.7.1 
Secondary Efficacy Variables 
The 
, and weekly number of 
symptom-free days will be summarized analogous to the primary endpoint, as a mean difference 
from Baseline (Visit 1) to weeks 4, 8,12, 16, 20, 22, 24, and 28. 
Number and percent of subjects receiving rescue medication will be summarized. 
13.7.2 
Safety 
Safety assessments will be based mainly on the nature, frequency, relationship, and severity of 
adverse events (AEs). AEs will be coded by primary system organ class (SOC) and preferred 
term (PT) according to the Medical Dictionary for Regulatory Activities (MedDRA). The 
treatment-emergent adverse events (TEAEs) will be summarized by the number and percentage 
of subjects in each SOC and PT. For summaries by relationship to study drug, “possibly related” 
will be combined with “related”, and “unlikely/remotely related” will be combined with “not 
related.” When multiple AEs are reported with the same preferred term, the AE of the strongest 
relation will be included in summary by relationship, and the AE of the most severe grade will be 
included in the summary by severity table. 
All AEs will be listed with onset/stop day, relationship to study drug, severity, action taken, and 
outcome. Pertinent subject information including cohort and demographics will also be included. 
Separate listings will be provided for TEAEs leading to study discontinuation and Treatment- 
emergent serious AEs (TESAEs). 
Laboratory data will be summarized by presenting summary statistics of raw data and change 
from baseline values (means, medians, standard deviations, ranges) and by presenting number 
and percentage of subjects with notable laboratory abnormalities. 
Data from other tests (vital signs) will be listed, notable values will be flagged, and any other 
information collected will be listed as appropriate. 
All safety and tolerability endpoints will be summarized. Baseline for all safety endpoints will be 
defined as the last recorded observation before the administration of AK002. 


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13.8 
Sample Size Calculation 
There is no formal statistical hypothesis testing specified for this study; this study is primarily 
designed to begin the characterization of the effect and safety and tolerability profile of AK002 
in subjects with CU. However, a total of 40 patients is typical for a first-in-indication study and 
should be adequate to pick up major safety signals should such signals indeed exist. 
14. 
Data Collection, Retention and Monitoring 
14.1 
Data Collection Instruments 
All staff at the study site will adhere to Good Documentation Practices. Data will be entered into 
CRFs using source document data. Source documents may include, but are not limited to 
laboratory data, recorded data from automated instruments, medical progress notes, and e-mail 
correspondence. 
14.2 
Data Management Procedures 
Data collection will be performed in accordance with 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 e-mail correspondence. The standard procedures for handling and processing records will be 
followed per GCP and the data management standard operating procedures. A comprehensive 
Data Management Plan will be developed and approved by the Sponsor. 
14.3 
Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation 
checks will be implemented and applied to the database on a regular basis. Queries are entered, 
tracked, and resolved through the electronic data capture system directly. The study database will 
be updated in accordance with the resolved queries. All changes to the study database will be 
documented. 
14.4 
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. 


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14.5 
Availability and Retention of Investigational Records 
In accordance with 21 CFR 312.62(c) and ICH/GCP 4.9.5 and all other applicable regulatory 
requirements, following completion or termination of the study, copies of all study records with 
limited access storage room, will be retained for a minimum of 2 years after notification that the 
investigations have been discontinued and the FDA has been notified, or for 2 years after all 
marketing applications have been approved. 
The trial master file will be created during the implementation phase of a study, maintained on 
an ongoing basis throughout the duration of the project and collated at the end of the study. The 
files will contain folders that may include, but are not limited to, the following subcategories: 
• 
Financial agreements 
• 
Regulatory documents 
• 
Independent ethics committee (IEC) Documents 
• 
Drug Accountability 
• 
Correspondence 
• 
Medical Reports 
• 
Patient Data 
• 
Monitoring Visit Reports 
• 
Sample CRFs and CRF 
14.6 
Data Monitoring 
Monitoring visits will be conducted by representatives of the Sponsor according to the United 
States CFR Title 21 Parts 50, 56, and 312 and ICH Guidelines for GCP (E6). By signing this 
protocol, the Investigator grants permission to the Sponsor (or designee), and appropriate 
regulatory authorities to conduct on-site monitoring and/or auditing of all appropriate study 
documentation.  
14.7 
Patient Confidentiality 
Only the patient number, patient initials, and demographics will be recorded in the eCRF. If the 
patient name appears on any source document collected by the Sponsor (e.g., hospital discharge 
summary), it must be removed from the document and the patient number and patient initials 
recorded on the source document before the document is transmitted to the Sponsor. 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 IEC to inspect their medical 
records to verify the information collected. Subjects will be informed that all personal 


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information made available for inspection will kept confidential and 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 patient’s identity will 
remain confidential. 
All study subjects will be advised not to share their study information with other subjects. 
15. 
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), IEC (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., the Health Insurance Portability and Accountability Act [HIPAA], 
European Union Data Protection Directive 95/46/EC). 
15.1 
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 IEC 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 patient; however, approval must be obtained as soon as possible thereafter. Any agreed 
amendments must also be signed by the Principal Investigator. 
15.2 
Institutional Review Board/Independent Ethics Committees 
The protocol and ICF will be reviewed and approved by the IRB/IEC of each participating center 
prior to study initiation. All SAEs, regardless of causality, will be reported to the IEC in 
accordance with the standard operating procedures and policies of the IRB/IEC, and the 
Investigator will keep the IRB/IEC informed as to the progress of the study. The Investigator will 
obtain assurance of IRB/IEC compliance with regulations. 
Any documents that the IRB/IEC may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, ICFs, information concerning patient 
recruitment, payment or compensation procedures, or other pertinent information) will be 
submitted to the IRB/IEC. The IRB/IEC’s written unconditional approval of the study protocol 
and the ICF will be in the possession of the Investigator before the study is initiated. The 
IRB/IEC’s unconditional approval statement will be transmitted by the Investigator to Allakos, 
Inc., prior to the shipment of study supplies to the site. This approval must refer to the study by 
exact protocol title and number and should identify the documents reviewed and the date of 
review. 


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Protocol and/or informed consent modifications or changes may not be initiated without prior 
written IRB/IEC approval except when necessary to eliminate immediate hazards to the subjects 
or when the change(s) involves only logistical or administrative aspects of the study. Such 
modifications will be submitted to the IRB/IEC and written verification that the modification 
was submitted and subsequently approved should be obtained. 
The IRB/IEC 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/IEC; new information that may affect 
adversely the safety of the subjects of the conduct of the study; an annual update and/or request 
for re-approval; and when the study has been completed. 
15.3 
Informed Consent Form 
Prior to screening, all subjects must consent to participate. 
In accordance with ICH GCP Guidelines E6 Section 4.3.3, subjects will be asked whether or not 
they would like their PCP notified of their study participation. 
The process of obtaining the informed consent will be in compliance with all federal regulations, 
ICH requirements, and local laws. 
The Investigator or a designee will review the study and the ICF with each patient. The review 
will include the nature, scope, procedures, and possible consequences of the patient's 
participation in the study. The consent and review must be in a form understandable to the 
patient. The Investigator or designee and the patient must both sign and date the ICF after review 
and before the patient can participate in the study. The patient will receive a copy of the signed 
and dated form, and the original will be retained in the site’s study files. The Investigator or 
designee must emphasize to the patient that study participation is entirely voluntary and that 
consent regarding study participation may be withdrawn at any time without penalty or loss of 
benefits to which the patient is otherwise entitled. 
In addition, prior to undergoing biopsies, subjects will provide informed consent in accordance 
with the standard operating procedures and policies of the investigational sites. 
15.4 
Publications 
The preparation and submittal for publication of manuscripts containing the study results shall be 
in accordance with a process determined by mutual written agreement among the study Sponsor 
and authors. The publication or presentation of any study results shall comply with all applicable 
privacy laws, including, but not limited to, HIPAA. 


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15.5 
Clinical Trial Registration 
This clinical trial will be registered on the “clinicaltrials.gov” clinical trial registry website as 
required by 121 STAT. 823. 
15.6 
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 patient’s signed ICF approved by the local IRB/IEC. No 
compensation beyond what is stated in the ICF is permitted. 
15.7 
Investigator’s Responsibilities 
By signing the Agreement of Investigator 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 (or investigation). 
3) Ensure that the requirements relating to obtaining informed consent and IEC review and 
approval meet federal guidelines. 
4) Report to the Sponsor or designee any adverse events that occur in the course of the study, 
in accordance with 21 CFR 312.64 and ICH 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 312.62 and ICH E6 and 
to make those records available for inspection with the Sponsor (or designee). 
7) Ensure that an IEC that complies with the requirements of 21 CFR part 56 and ICH E6 will 
be responsible for initial and continuing review and approval of the clinical study. Promptly 
report to the IEC all changes in the research activity and all unanticipated problems 
involving risks to subjects or others (to include amendments and IND safety reports). 
8) Seek IEC approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the subjects. 
9) 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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16. 
References 
Altrichter S, Koch K, Church M, Maurer M. Atopic predisposition in cholinergic urticaria 
patients and its implications. J Eur Acad Dermatol Venereol, 2016;30:2060–65. 
Borzova E, Rutherford A, Konstantinou G, Leslie K, Grattan C. Narrowband ultraviolet B 
phototherapy is beneficial in antihistamine-resistant symptomatic dermographism: a pilot 
study. J Am Acad Dermatol, 2008;59:752–7. 
Boyman O, Kaegi C, Akdis M, Bavbek S, Bossios A, Chatzipetrou A, et al. EAACI IG 
Biologicals task force paper on the use of biologic agents in allergic disorders. Allergy, 
2015;70:727–54. 
Falahati R, Bright J, Dorenbaum A, Bebbington C, Tomasevic N, Lidke D, et al. A recombinant 
antibody to Siglec-8 shows selective ADCC activity against mast cells from systemic 
mastocytosis patients. Am Assoc Hematol, 2015 Annual Meeting, Abstract 4092. 
Finlay A, Khan G. Dermatology Life Quality Index (DLQI)--a simple practical measure for 
routine clinical use. Clin Exp Dermatol, 1994;19(3):210–16. 
Godse K, Farooqui S, Nadkarni N, Patil S. Prevalence of cholinergic urticaria in Indian adults. 
Indian Dermatol Online J, 2013;4(1):62–63. 
Hellgren L. The prevalence of urticaria in the total population. Acta Allergol, 1972;27(3):236-40. 
Hiragun T, Ishii K, Hiragun M, Suzuki H, Kan T, Mihara S, et al. Fungal protein MGL_1304 in 
sweat is an allergen for atopic dermatitis patients. J Allergy Clin Immunol, 
2013;132(3):608–15 e604. 
James C, Paulson B, Bochnera B. Siglec-8 as a drugable target to treat eosinophil and mast cell 
associated conditions. Pharmacol Ther, 2012;135(3):327–36. 
Koch K, Weller K, Werner A, Maurer M, Altrichter S. Antihistamine updosing reduces disease 
activity in patients with difficult-to-treat cholinergic urticaria. J Allergy Clin Immunol, 
2016;138(5):1483–85 e1489. 
Maurer M, Weller K, Bindslev-Jensen C, Gimenez-Arnau A, Bousquet P, Bousquet J, et al. 
Unmet clinical needs in chronic spontaneous urticaria. A GA(2)LEN task force report. 
Allergy, 2011;66(3):317–30. 


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Maurer M, Rosén K, Hsieh H, Saini S, Grattan C, Gimenéz-Arnau A, et al. Omalizumab for the 
treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med, 
2013;368(10):924–35. 
Metz M, Maurer M. Omalizumab in chronic urticaria. Curr Opin Allergy Clin Immunol, 
2012;12(4):406–11. 
Metz M, Ohanyan T, Church M, Maurer M. Omalizumab is an effective and rapidly acting 
therapy in difficult-to-treat chronic urticaria: a retrospective clinical analysis. J Dermatol 
Sci, 2014;73(1):57–62. 
Metz M, Ohanyan T, Church M, Maurer M. Retreatment with omalizumab results in rapid 
remission in chronic spontaneous and inducible urticaria. JAMA Dermatol, 
2014;150(3):288–90. 
Mlynek A, Magerl M, Hanna M, Lhachimi S, Baiardini I, Canonica G, et al. The German version 
of the Chronic Urticaria Quality-of-Life Questionnaire: factor analysis, validation, and 
initial clinical findings. Allergy, 2009;64(6):927–36. 
Nutku E, Hudson S, Bochner B. Mechanism of Siglec-8-induced human eosinophil apoptosis: 
Role of caspases and mitochondrial injury. Biochem Biophys Res Commun, 
2005;336:918–24. 
Nutku-Bilir E, Hudson S, Bochner B. Interleukin-5 priming of human eosinophils alters 
Siglec-8-mediated apoptosis pathways. Am J Respir Cell Mol Biol, 2008;38:121-24. 
Petalas K, Kontou-Fili K, Gratziou C. Bronchial hyperresponsiveness in patients with 
cholinergic urticaria. Ann Allergy Asthma Immunol, 2009;102(5):416–21. 
Saini S, Bindslev-Jensen C, Maurer M, Grob J, Bulbul B, Bradley M, et al. Efﬁcacy and safety of 
omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain 
symptomatic on H1 Antihistamines: a randomized, placebo-controlled study. 
J Invest Dermatol, 2015;135:67–75. 
Sampson H, Munoz-Furlong A, Campbell R, Adkinson N, Jr., 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. 
Sussman G, Hebert J, Barron C, Caron-Guay R, Laflamme S, Stern S. Real life experience with 
omalizumab for the treatment of chronic urticaria. Ann Allergy Asthma Immunol, 
2014;112:170–74. 


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Takahagi S, Tanaka T, Ishii K, Suzuki H, Kameyoshi Y, Shindo H, Hide M. Sweat antigen 
induces histamine release from basophils of patients with cholinergic urticaria associated 
with atopic diathesis. Br J Dermatol, 2009;160(2):426–28. 
Wallengren J, Isaksoon A. Urticarial dermographism: clinical features and response to 
psychosocial stress. Acta Derm Venereol, 2007;87:493–8. 
Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica G, et al. The 
EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, 
and management of urticaria: the 2013 revision and update. Allergy, 2014;69(7):868–87. 
Zuberbier T, Althaus C, Chantraine-Hess S, Czarnetzki B. Prevalence of cholinergic urticaria in 
young adults. J Am Acad Dermatol, 1994;31(6):978–81. 
Zuberbier T, Asero R, Bindslev-Jensen C, Canonica G, Church M, Gimenez-Arnau A, et al. 
EAACI/GA(2)LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 
2009;64:1427–43. 
 


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17. 
Appendices 
17.1 
Appendix 1: Sampson’s Criteria for 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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17.2 
Appendix 2: Procedures for Extended Dosing (Optional) 
Summary of Extended Dosing 
Subjects in the CholU, UF, and CSU-XOLAIR® (omalizumab) failure cohorts who received all 
6 infusions of AK002, were followed through Day 155, and demonstrated severe symptoms of 
urticaria following discontinuation of treatment will be allowed the option to receive extended 
dosing with up to 12 additional doses of AK002.  
For extended dosing, subjects must have a baseline (Day 1) UCT of ≤5 and a week 22 (Day 155) 
UCT of ≥12 (Complete Response). They must have a UCT of ≤5 between Day 155 and Day 309 
(i.e., within 6 months from last dose). All subjects that decide to receive the extended dosing will 
start with a dose of 0.3 mg/kg, followed by possible dose increases to 1 mg/kg and 3 mg/kg for 
subsequent infusions. The Investigator in consultation with the Medical Monitor may increase 
the dose to 6 mg/kg and then to 10 mg/kg if they think that the patient has not received benefit 
from the lower doses. 
Extended dosing will include a Screening Period of 2 to 3 weeks, a Treatment Period of 
44 weeks, and a Follow-up Period of 8 weeks after the last dose of study drug. During the 
Screening Period, subjects will receive a standard oral dose of a second-generation 
H1-antihistamine once daily, with on-demand dosing of up to 3 additional tablets per day. 
During the Treatment Period, subjects will continue daily dosing with the second-generation 
H1-antihistamine (standard dose once daily with on-demand dosing of up to 3 additional tablets 
per day) and AK002 administered by IV infusion on Extended Dosing Days 1, 29, 57, 85, 113, 
141, 169, 197, 225, 253, 281, and 309. Subjects will be followed for 8 weeks after the last dose 
of study drug (Follow-up Period). Safety assessments and response to study drug will be 
evaluated throughout the study. The optional extended dosing period is outlined in Table 8.  


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Table 8 
Extended Dosing Period 
Description 
Screening 
Period 
Treatment Period 
AK002 Dose (mg/kg)† 
Follow-up 
Period 
0.3 
1 
1 
3* 
3* 
3* 
3* 
3* 
3* 
3* 
3* 
3* 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Week 
-3 to -2 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
52 
Extended 
Dosing Day 
-21 to -14 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
365 
* Increase to 3 mg/kg if UCT score is <12 and/or at the discretion of the Investigator in consultation with the 
Allakos Medical Monitor. If UCT score is ≥12, and if the Investigator in consultation with the Allakos Medical 
Monitor thinks that the subject has experienced adequate symptom improvement, then continue with the 1 mg/kg 
dose. The Investigator in consultation with the Medical Monitor may increase the dose to 6 mg/kg and then to 
10 mg/kg if they think that the patient has not received benefit from the lower doses. 
† The Investigator in consultation with the Allakos Medical Monitor, can chose to maintain the patient’s last 
administered dose depending on how much time has lapsed between Week 20/last dose under main study and first 
dose under extension.  
Based on the subject’s weight, the designated clinical staff will prepare the appropriate dilution 
of AK002 for IV administration at 0.3 mg/kg for Extended Dosing Day 1, 1 mg/kg for Extended 
Dosing Days 29 and 57, and either 1 mg/kg or 3 mg/kg (depending on UCT score and 
Investigator discretion) for Extended Dosing Days 85, 113, 141, 169, 197, 225, 253, 281, and 
309.  
The Investigator in consultation with the Allakos Medical Monitor, can chose to maintain the 
patient’s last administered dose depending on how much time has lapsed between Week 20/last 
dose under main study and first dose under extension.  
The Investigator in consultation with the Medical Monitor may increase the dose to 6 mg/kg and 
then to 10 mg/kg if they think that the patient has not received benefit from the lower doses. 
Objective 
To evaluate the long-term safety and tolerability of up to 12 additional doses of AK002 in 
subjects with CU. 


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Entry Criteria 
Inclusion Criteria 
1) Adults (≥18 and ≤85 years old) 
2) Body weight <125 kg 
3) Provide signed and dated informed consent  
4) Enrolled in either the CU, UF, or CSU-XF cohorts  
5) Completed 6 infusions of AK002 and with follow-up through Day 155 [Week 22]) and 
willing to begin extended dosing upon qualification 
6) Must have a baseline (Day 1) UCT of ≤5 and a week 22 (Day 155) UCT of ≥12 (Complete 
Response). They must have a UCT of ≤5 post-week 22 (Day 155) and by week 44 
(Day 309) i.e., within 6 months from last dose. 
6) Uncontrolled CU (UCT <12) for at least 2 weeks prior to the time of enrollment into the 
extension 
7) Able to read, understand, and willing to sign the informed consent form and comply with 
study procedures 
8) Willing, committed, and able to return for all clinic visits and complete all study-related 
procedures, including willingness to have IV infusion of study drug administered by a 
qualified person 
9) Females of childbearing potential must have a negative pregnancy test at Baseline. Female 
subjects must be willing to use highly effective contraception (Pearl-4 Index <1) or abstain 
from sexual activity from screening until the end of the study, or for 120 days following the 
last dose of study drug, whichever is longer. A woman will be considered not of 
childbearing potential if she is post-menopausal for greater than 2 years (FSH >40 mL) or 
surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). 
 
Male subjects with female partners of childbearing potential must agree to use a highly 
effective method of contraception from screening until the end of the study or for 120 days 
following the last dose of study drug, whichever is longer. All fertile men with female 
partners of childbearing potential should be instructed to contact the Investigator 
immediately if they suspect their partner might be pregnant (e.g., missed or late menstrual 
period) at any time during study participation. 
10) No participation in clinical trials 4 weeks before participation in this study 


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Exclusion Criteria 
1) Acute urticaria 
2) Concurrent/ongoing treatment with immunosuppressives (e.g., cyclosporine, methotrexate, 
dapsone, or others) within 4 weeks or 5 half-lives prior to Baseline, whichever is longer 
3) Significant medical condition rendering the subject immunocompromised or not suitable for 
a clinical trial 
4) Significant concomitant illness that would adversely affect the subject’s participation or 
evaluation in this study 
5) History of malignancies within 5 years prior to screening other than a successfully treated 
non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cancer 
6) Presence of clinically significant laboratory abnormalities 
7) Lactating women or pregnant women 
8) Substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) 
within the last 5 years that could limit the subject’s ability to comply with study procedures 
9) Subjects who are detained officially or legally to an official institute or those that have been 
committed to an institution by an order issued either by the judicial or the administrative 
authorities will be excluded 
10) Use of omalizumab within 2 months prior to Baseline 
11) Receipt of IV IgG therapy 30 days prior to Baseline 
12) Plasmapheresis 30 days prior to Baseline 
13) Use (daily or every other day) of doxepin 14 days prior to Baseline 
14) Receipt of inactive vaccination or live attenuated vaccine 30 days prior to Baseline 
15) Use of H2-antihistamines 7 days prior to Baseline 
16) Intake of leukotriene antagonists within 7 days prior to Baseline 
17) Intake of systemic corticosteroids (e.g., oral or depot) within 14 days prior to Baseline 
18) Positive screening for ova and parasite test at Baseline 
19) Treatment of helminthic parasite within 6 months of screening 


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20) Positive human immunodeficiency virus serology at screening 
21) Positive hepatitis serology at Baseline, except for vaccinated subjects or subjects with past 
but resolved hepatitis at screening 
22) Donation or loss of >500 mL of blood within 56 days prior to administration of study drug 
or donation of plasma within 7 days prior to administration of drug 
23) Known hypersensitivity to any ingredients of AK002 or drugs related to AK002 (e.g., 
monoclonal antibodies, polyclonal gamma globulin) 
Procedures 
Subjects will maintain the same patient identification number during extended dosing. Unless 
specified otherwise, the procedures and methods performed during the initial 6 infusions will 
continue through extended dosing. This includes but is not limited to fasting requirements, 
prohibited medications, allowed medications, rescue medications, dose preparation, dose 
administration, AK002 storage and accountability, dietary and lifestyle restrictions, adverse 
event reporting, and serious adverse event reporting. 
The site will obtain written informed consent for extended dosing. All subjects who sign an 
informed consent for extended dosing will be recorded in the EDC. A subject is considered 
enrolled in extended dosing at the time for the first infusion. 
The schedule of assessments for extended dosing is provided in Table 9. 
General Safety Monitoring 
The Investigators and Medical Monitor will review data relating to safety and conduct of the 
study throughout the course of extended dosing.  
Study Stopping Rules 
Access to extended dosing will be discontinued prematurely in the event of any of the following:  
• 
A life-threatening AE that is possibly or probably related to treatment as determined by the 
Medical Monitor 
• 
A fatal AE that is possibly or probably related to treatment as determined by the Medical 
Monitor 
• 
New information leading to unfavorable risk-benefit judgment of the study drug, e.g., 
occurrence of significant previously unknown adverse reactions or unexpectedly high 
intensity or incidence of known adverse reactions, or other unfavorable safety findings 


Protocol AK002-006 
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Date: 04 Dec 2018 
Allakos, Inc. 
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• 
Sponsor’s decision that extended dosing is unjustifiable for medical or ethical reasons 
• 
Discontinuation of development of AK002 
Health Authorities and IRB/IECs will be informed regarding discontinuation of access to 
extended dosing in accordance with applicable regulations. Access to extended dosing may be 
terminated or suspended on request of Health Authorities. 
Data Management Procedures 
Data for all subjects who sign an informed consent for extended dosing will be recorded in 
eCRFs designated for extended dosing and will be separate from eCRFs completed for the initial 
6 infusions. The database for the initial 6 infusions will be separate from the database for 
extended dosing, which will allow for database lock of the data obtained for the initial 
6 infusions prior to completion of extended dosing. The database for extended dosing will be 
locked after all subjects have completed/discontinued extended dosing. 
 


Protocol AK002-006 
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Allakos, Inc. 
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Table 9 
Schedule of Assessments for Extended Dosing 
Description 
Screening 
Period 
Treatment Period 
Follow-up Period 
Visit 1 
Visit 2 
Visits 3-13 
Visit 14 
Ext Day -21 to  
Ext Day -14 
Ext Day 1 
 
Ext Days 29, 57, 85, 113, 141, 169, 197,  
225, 253, 281, 309 (± 2) 
Ext 365 (± 3) or ET 28 (± 3) Days 
After Last Dose 
Week -3 to -2 
Week 0 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 
Week 52 
Screening 
Baselinea/Dosing 
Dosing 
End of Study/ET 
Informed consent 
x 
 
 
 
Eligibility assessment/ 
confirmation 
x 
x 
 
 
Demographic data 
x 
 
 
 
Medical history 
x 
 
 
 
Prior CU treatment 
x 
 
 
 
Prior/concomitant medication 
x 
x 
x 
x 
Rescue medication use 
 
x 
x 
x 
Study drug administrationb 
 
x 
x 
 
Patient diary 
x 
x 
x 
x 
 
 
x 
x 
x 
UCT 
 
x 
x 
x 
 
 
x 
x 
x 
 
 
x 
x 
x 
CBC with differentiale 
 
x (pre-dose) 
x 
x 
Blood chemistry 
 
x (pre-dose) 
x (pre-dose) 
x 
Blood sample for PKf 
 
x (pre-dose) 
 
x 
Blood sample for ADAg 
 
x (pre-dose) 
x (pre-dose) 
x 
Serologyh 
x 
 
 
 
Urinalysisi 
 
x 
 
x 


Protocol AK002-006 
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Date: 04 Dec 2018 
Allakos, Inc. 
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Table 9 
Schedule of Assessments for Extended Dosing 
Description 
Screening 
Period 
Treatment Period 
Follow-up Period 
Visit 1 
Visit 2 
Visits 3-13 
Visit 14 
Ext Day -21 to  
Ext Day -14 
Ext Day 1 
 
Ext Days 29, 57, 85, 113, 141, 169, 197,  
225, 253, 281, 309 (± 2) 
Ext 365 (± 3) or ET 28 (± 3) Days 
After Last Dose 
Week -3 to -2 
Week 0 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 
Week 52 
Screening 
Baselinea/Dosing 
Dosing 
End of Study/ET 
Urine pregnancy 
 
x 
x 
x 
Serum pregnancyj 
x 
 
 
 
Stool for ova and parasite 
x 
 
 
 
Physical examinationc 
xk 
xl 
xl 
xk 
Vital signsm 
x 
x 
x 
x 
Weight 
x 
x 
x 
x 
12-lead ECGn 
x 
 
 
x 
Adverse eventso 
 
x 
x 
x 
Table 9 Notes 
Ext: Extended 
a) Baseline is defined as up to 48 hours prior to first dose. 
b) AK002 will be administered as a single peripheral IV infusion at a dose of 0.3 mg/kg (Dose 1) on Extended Dosing Day 1. If well tolerated, the dose will be increased to 
1 mg/kg on Extended Dosing Days 29 (Dose 2) and 57 (Dose 3). The dose will be increased to 3 mg/kg for doses 4 through 12 The Investigator in consultation with the 
Medical Monitor can up dose to 3 mg earlier than dose 4 if needed. (Extended Dosing Days 85, 113, 141, 169, 197, 225, 253, 281, and 309, respectively) if the subject has a 
UCT score <12, and/or at the discretion of the Investigator in consultation with the Allakos Medical Monitor. If the UCT score is ≥12, and if the Investigator in consultation 
with the Medical Monitor feels that the subject has received adequate symptom improvement, the subject will remain at the 1 mg/kg dose. All doses will be administered over 
a period of approximately 4 hours, although the duration of infusion and the rate at which the infusion is given may be adjusted based on Investigator discretion. Please refer to 
the Pharmacy Manual for detailed instructions on preparations, administration, and infusion rate. The Investigator in consultation with the Medical Monitor may increase the 
dose to 6 mg/kg and then to 10 mg/kg if they think that the patient has not received benefit from the lower doses. 
c) During the physical exam the evaluating physician will also ask subjects to rate the intensity of their atopic disease on a scale of 0–10; 0 (no symptoms) to 10 (worst possible 
symptoms). 
d) Subjects should complete the 
 on a weekly basis. On weeks where a clinic visit is not scheduled, the 
 should be completed at home.  


Protocol AK002-006 
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Allakos, Inc. 
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e) Blood for CBC with differential, including absolute blood eosinophil and basophil counts, will be obtained just prior to each infusion, 1 hour after the end of each infusion, 
and on Extended Dosing Day 365 (or ET). 
f) 
If possible, blood for PK analysis should be obtained from the arm not used for study drug infusion. 
g) ADA will be obtained Visits 2, 3, 5, 8 and 10. An unscheduled ADA blood sample may be obtained if an immunogenicity-related AE is suspected. 
h) Serology at screening includes hepatitis B surface antigen, hepatitis C antibody, hepatitis B core antibody, and human immunodeficiency virus. 
i) 
At screening, include urine drug screening (alcohol, amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, 
methaqualone, opiates, phencyclidine) and urine cotinine tests. 
j) 
Blood for serum pregnancy test at Screening Visit. 
k) A complete PE will be performed by either the Investigator or designee as noted in Section 10.5.2. 
l) 
A symptom-directed PE, including assessments of possible infusion site reactions, will be performed by the Investigator or designee as needed. 
m) Vital signs, including supine systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate, will be taken after the subject has been in the supine position 
for ≥5 minutes and before any blood draw. On AK002 dosing days, vital signs will be measured pre-dose and at the end of infusion. 
n) 12 lead ECGs must be recorded after 10 minutes rest in the supine position. 
o) All AEs identified, whether serious or non-serious, will be recorded in the eCRF until Day 365 (± 3) or ET 28 (± 3) days after last dose 
 

SAP_001.pdf: 
An Open-Label, Pilot Study to Assess the Efficacy and Safety of AK002 (Siglec-8) in Subjects 
with Antihistamine-Resistant Chronic Urticaria 
NCT Number: NCT03436797 
Document Date: 13 February 2019 
 


 
 
Page 1 of 51 
Statistical Analysis Plan 
Protocol Title 
An Open-Label, Pilot Study to Assess the Efficacy and Safety of 
AK002 (Siglec-8) in Subjects with Antihistamine-Resistant 
Chronic Urticaria 
Protocol Number  
AK002-006  
Protocol Version 
Amendment 4/4.1 
Protocol Date 
11 January 2019 
Study Drug 
AK002 
Study Phase 
2a 
IND Number 
137491 
EUDRACT Number 
2017-002581-51 
Sponsor  
Allakos, Inc. 
975 Island Drive, Suite 201 
Redwood City, CA  94065 USA 
SAP Version 
1.1 
Date 
13 February 2019  
 
 






Protocol AK002-006 
Statistical Analysis Plan (Version 1.1) 
Date: 13 February 2019 
Allakos, Inc. 
Page 3 of 51 
Confidential 
Table of Contents 
Statistical Analysis Plan ................................................................................................................1 
Signature Page ................................................................................................................................2 
Table of Contents ...........................................................................................................................3 
List of Tables ..................................................................................................................................6 
List of Abbreviations .....................................................................................................................7 
Revision History .............................................................................................................................9 
1. 
Introduction ........................................................................................................................10 
2. 
Study Objectives .................................................................................................................10 
2.1 
Primary Objective ....................................................................................................10 
2.2 
Secondary Objectives ...............................................................................................10 
3. 
Study Design .......................................................................................................................10 
3.1 
General Description ..................................................................................................10 
3.2 
Study Treatment .......................................................................................................17 
3.2.1 
Treatment, Dose, and Mode of Administration .........................................17 
3.2.2 
Duration of Study .......................................................................................17 
3.3 
Methods of Assigning Subjects to Treatment Group ...............................................17 
3.4 
Blinding ....................................................................................................................18 
3.5 
Hypotheses ...............................................................................................................18 
3.6 
Determination of Sample Size ..................................................................................18 
3.7 
Changes to Analyses Planned in the Protocol ..........................................................18 
3.8 
Efficacy Assessments ...............................................................................................18 
3.8.1 
Urticaria Patient Daily Diary ..................... Error! Bookmark not defined. 
3.8.2 
Urticaria Control Test ................................................................................20 
3.8.3 
 .................................20 
3.8.4 
 .......................................21 
3.8.5 
 ...................21 
3.8.6 
 ...............................................21 
3.8.7 
 ................................................................21 
3.8.8 
 ............................................21 


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Statistical Analysis Plan (Version 1.1) 
Date: 13 February 2019 
Allakos, Inc. 
Page 4 of 51 
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3.8.9 
 ................................................................22 
3.8.10 
 .....................................................................................22 
3.8.11 
Additional Measures for Disease Activity and Functional Status .............22 
3.9 
Safety Assessments ..................................................................................................23 
3.9.1 
Physical Examination.................................................................................23 
3.9.2 
Vital Signs, Height and Weight .................................................................23 
3.9.3 
Laboratory Tests ........................................................................................23 
3.9.4 
Anti-Drug-Antibodies ................................................................................23 
3.9.5 
Electrocardiogram ......................................................................................23 
3.9.6 
Pregnancy Testing ......................................................................................23 
3.9.7 
Tolerability/Acceptability ..........................................................................23 
3.9.8 
Medical History and Adverse Events (AEs) ..............................................24 
3.9.9 
Prior, Concomitant, and Prohibited Medications .......................................24 
4. 
Definitions ...........................................................................................................................25 
5. 
Efficacy and Safety Variables ...........................................................................................25 
5.1 
Primary Endpoint .....................................................................................................25 
5.2 
Secondary Endpoints ................................................................................................26 
5.3 
Exploratory Endpoints ..............................................................................................26 
5.4 
PD Endpoint .............................................................................................................26 
5.5 
Pharmacokinetic Endpoint .......................................................................................26 
6. 
Statistical Methods .............................................................................................................26 
6.1 
General Methodology ...............................................................................................27 
6.2 
Visit Window and Unscheduled Assessments .........................................................28 
6.3 
Adjustment for Covariates .......................................................................................28 
6.4 
Handling of Dropouts, Missing Data, and Data Discrepancies ................................28 
6.5 
Interim Analysis .......................................................................................................28 
6.6 
Timing of Final Analyses .........................................................................................29 
6.7 
Multicenter Study .....................................................................................................29 
6.8 
Multiple Comparisons/Multiplicity Adjustment ......................................................29 
6.9 
Examination of Subgroups .......................................................................................29 


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Statistical Analysis Plan (Version 1.1) 
Date: 13 February 2019 
Allakos, Inc. 
Page 5 of 51 
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7. 
Statistical Analysis ..............................................................................................................29 
7.1 
Analysis Populations ................................................................................................29 
7.1.1 
Modified Intent-to-treat Population ...........................................................29 
7.1.2 
Safety Population .......................................................................................29 
7.1.3 
Per-Protocol Population .............................................................................29 
7.2 
Disposition of Subjects .............................................................................................30 
7.3 
Protocol Deviations ..................................................................................................30 
7.4 
Demographics and Baseline Subject Characteristics ...............................................30 
7.5 
Baseline Disease Characteristics ..............................................................................30 
7.6 
Treatments ................................................................................................................31 
7.6.1 
Treatment Compliance and Extent of Exposure ........................................31 
7.6.2 
Prior and Concomitant Medications ..........................................................31 
7.7 
Efficacy Analyses .....................................................................................................31 
7.7.1 
Primary Efficacy Analysis .........................................................................31 
7.7.1.1  Per Protocol Analysis ............................................................................. 32 
7.7.1.2  Subgroup Analysis .................................................................................. 32 
7.7.1.3  Secondary Efficacy Analyses ................................................................. 32 
7.7.2 
Exploratory Efficacy Analyses ..................................................................32 
7.8 
Pharmacodynamic Analysis .....................................................................................33 
7.9 
Pharmacokinetic Analysis ........................................................................................33 
7.10 
Safety Analyses ........................................................................................................33 
7.10.1 
Adverse Events ..........................................................................................33 
7.10.2 
Laboratory Test ..........................................................................................34 
7.10.3 
ECG............................................................................................................34 
7.10.4 
Vital Signs and other safety measures .......................................................35 
8. 
Validation ............................................................................................................................35 
9. 
References ...........................................................................................................................36 
10. 
Appendices ..........................................................................................................................37 
10.1 
Appendix A: Exclusion Criteria for the Per Protocol Populations ...........................37 
10.2 
Appendix B.1.1: Urticaria Patient Daily Diary for Patient with 
Cholinergic Urticaria ................................................................................................37 


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Allakos, Inc. 
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10.3 
Appendix B.1.2: Urticaria Patient Daily Diary for Patient with Urticaria Factitia ..38 
10.4 
Appendix B.1.3 Urticaria Patient Daily Diary for Patients with Chronic 
Spontaneous Urticaria ..............................................................................................39 
10.5 
Appendix B.2: Urticaria Control Test ......................................................................40 
10.6 
Appendix B.3 
 ...............................................41 
10.7 
Appendix B.4: 
 .............................43 
10.8 
Appendix B.5: 
 .........44 
10.9 
Appendix B.6: 
 ....................................46 
10.10  Appendix B.7: 
 .....................................................47 
10.11  Appendix B.8: 
 .............................................................49 
10.12  Appendix C: List of Tables, Listings, and Figures ..................................................50 
10.13  Appendix D: Table and Listing Shells .....................................................................51 
 
 
List of Tables 
Table 1 
Schedule of Assessments ............................................................................................11 
Table 2 
Patient-Reported Outcome Instruments for Efficacy Assessment ..............................20 
Table 3 
Terminology and Definition .......................................................................................25 
 


Protocol AK002-006 
Statistical Analysis Plan (Version 1.1) 
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Allakos, Inc. 
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List of Abbreviations  
AE 
Adverse event 
 
 
AH 
Antihistamine 
ATC 
Anatomical-Therapeutic-Chemical 
CholU 
Cholinergic Urticaria 
 
 
 
 
CI 
Confidence Interval 
CMR 
Clinically Meaningful Response 
CR 
Complete response 
CRF 
Case Report Form 
CSR 
Clinical study report 
CSU 
Chronic Spontaneous Urticaria 
CSU-XN 
Chronic Spontaneous Urticaria – Xolair Naïve 
CSU-XF 
Chronic Spontaneous Urticaria – Xolair Failure 
CU 
Chronic Urticaria 
 
 
DC 
Disease Control 
 
 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
FSH 
Follicle-Stimulating Hormone 
ICH 
International Conference on Harmonization 
ICF 
Informed Consent Form 
IgE 
Immunoglobulin E 
IRB 
Institutional Review Board 
IV 
Intravenous (ly) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MCIR 
Minimally Clinically Important Response 
MCID 
Minimally Clinically Important Difference 
PK 
Pharmacokinetics 
PP 
Per-Protocol population 
PR 
Partial response 
PT 
Preferred term 
p-value 
Probability value 
QoL 
Quality of Life 


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Statistical Analysis Plan (Version 1.1) 
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Allakos, Inc. 
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SAE 
Serious adverse event 
SD 
Standard deviation 
 
 
SAP 
Statistical Analysis Plan 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
TESAE 
Treatment-emergent serious adverse event 
UAS 
Urticaria Activity Score 
UAS7 
Weekly Urticaria Activity Score 
UCT 
Urticaria Control Test 
UF  
Urticaria Factitia 
UPDD 
Urticaria Patient Daily Diary 
WHO 
World Health Organization 
WHODD 
World Health Organization Drug Dictionary 
 
 


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Statistical Analysis Plan (Version 1.1) 
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Allakos, Inc. 
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Revision History 
Version Date 
Version Number 
Description 
31 Aug 2018 
1 
First version of the Statistical Analysis Plan 
13 Feb 2019 
1.1 
Add clarifications and incorporate changes needed per the protocol 
amendments 
 
 


Protocol AK002-006 
Statistical Analysis Plan (Version 1.1) 
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1. 
Introduction 
This statistical analysis plan (SAP) describes the rules and conventions to be used in the analysis 
and presentation of efficacy and safety data as planned for the clinical protocol. It describes, in 
detail, the data and variables to be summarized or analyzed, including specifications of the 
analytical methods to be performed. The statistical analysis plan presented in this document will 
supersede the statistical analysis methods described in the clinical protocol. 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). This SAP is based on 
the clinical study protocol AK002-006, Amendment 4/4.1, dated 11 Jan 2019 and its associated 
electronic case report forms (eCRF).  
2. 
Study Objectives  
2.1 
Primary Objective 
The primary objective is to assess the efficacy and safety of AK002 in subjects with Chronic 
Urticaria (CU). Efficacy will be assessed by the urticaria control test [UCT] score.  
2.2 
Secondary Objectives 
The secondary objectives of the study are to assess other measures of efficacy and 
pharmacodynamics of AK002. 
3. 
Study Design 
3.1 
General Description 
This is an open-label, pilot study to assess the efficacy and safety of AK002 in subjects with 
antihistamine-resistant chronic urticaria. The study comprises a screening period of 4 weeks, with 
daily oral intake of standard-dose (once daily) second-generation antihistamine (AH) (standard of 
care, with on-demand intake of up to 3 additional AH tablets per day). The treatment period 
comprises a daily oral intake of standard-dose second-generation AH and AK002 administered by 
IV infusion at Days 1, 29, 57, 85, 113, and 141. The primary and secondary endpoints will be 
evaluated at Week 10, 2 weeks after last dose, for subjects enrolled under Protocol Amendment 
2.1 and Week 22, 2 weeks after last dose, for all remaining subjects (i.e., those on study during 
Protocol Amendment 3), and then patients will be followed for an additional 4 weeks (Week 24). 
The study design is presented schematically in Table 1. 
 




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Statistical Analysis Plan (Version 1.1) 
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Table 1 
Scheduled of Assessments (continued) 
Description 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visits 5, 6, 7 
Visit 8 
Visit 9 
Visit 10 
Day -28 
 
Day 1 
 
Day 29 
(± 2) 
Day 57 
(± 2) 
Days 85, 113, 
and 141 (± 2) 
Day 155 
(± 2) 
Day 169 
(± 2) 
Day 197 
(± 2) 
Week -4 
Week 0 
Week 4 
Week 8 
Weeks 12, 16, 
and 20 
Week 22 
Week 24 
Week 28 
Screening 
Baseline/Dosing 
Dosing 
Dosing 
Dosingr 
Response 
Assessmentt 
Response 
Assessment 
End of Study/ 
Early Term. 
Anti-drug antibodiesf 
 
x 
x 
 
x 
x 
 
x 
PK analysisf 
 
x 
x 
 
x 
x 
 
x 
Blood safetyg 
x 
x 
x 
x 
x 
x 
x 
x 
Blood biomarkerso 
 
x 
x 
x 
x 
x 
x 
x 
Serologyh 
x 
 
 
 
 
 
 
 
Urinalysis 
xi 
x 
x 
x 
x 
x 
x 
x 
Urine pregnancy 
 
x 
x 
x 
x 
x 
x 
x 
Serum pregnancyj 
x 
 
 
 
 
 
 
 
Stool for ova and parasite 
x 
 
 
 
 
 
 
 
Physical examinations 
xk 
xl 
xl 
xl 
xl 
xl 
xl 
xl 
Vital signsm 
x 
x 
x 
x 
x 
x 
x 
x 
Weight 
x 
x 
x 
x 
x 
x 
x 
x 
12-lead ECGn 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events 
 
x 
x 
x 
x 
x 
x 
x 
Table 3 Notes 
a) 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 ID number and re-screened once. 
Subjects re-screened within 30 days of signing the initial consent will not need to sign a new ICF providing there have been no changes to the ICF. 
b) Baseline is defined as up to 48 hours prior to first dose. 
c) AK002 will be administered as a single peripheral IV infusion. Please refer to the Pharmacy Manual for detailed instructions on preparations, administration, and infusion rate. 
d) Subjects should complete the 
 on a weekly basis. On weeks where a clinic visit is not scheduled, the 
should be completed at home.  


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Statistical Analysis Plan (Version 1.1) 
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Table 3 Notes (continued) 
e) Subjects will be administered only the instruments that are relevant to their condition (see Error! Reference source not found.). FricTest will be assessed, if relevant, at every 
visit. The PCE can be performed at Visit 1 for diagnostic reasons and will be assessed at Visits 2 (at least 24 hours prior to dose), 8, and 10 only.  
f) 
ADA will be obtained Visits 2, 3, 5, 8 and 10. An unscheduled ADA blood sample may be obtained if an immunogenicity-related AE is suspected. PK will be analyzed 
retroactively using backup blood samples. 
g) Hematology, Chemistry and CBC with differential. 
h) Serology at Screening includes hepatitis B surface antigen (HBsAG), hepatitis C antibody, hepatitis B core antibody (anti-HBc), and human immunodeficiency virus (HIV). 
i) 
At Screening, include urine drug screening (alcohol, amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, 
methaqualone, opiates, phencyclidine) and urine cotinine tests. 
j) 
Blood for serum pregnancy tests at Screening Visit; blood for FSH is to be obtained only to confirm post-menopausal status. 
k) A complete PE will be performed by either the Investigator or designee as noted in Section Error! Reference source not found.. 
l) 
A symptom-directed PE, including assessments of possible infusion site reactions, will be performed by the Investigator or designee as needed. 
m) Vital signs, including supine systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate, will be taken after the patient has been in the supine position 
for ≥5 minutes and before any blood draw. On AK002 dosing days, vital signs will be measured pre-dose and at the end of infusion. 
n) 12 lead electrocardiograms (ECGs) must be recorded after 10 minutes rest in the supine position. 
o) Includes total IgE, absolute basophil and absolute blood eosinophil counts. Serum and plasma samples will be stored at -80°C for post hoc analysis of exploratory biomarkers. 
p) Skin biopsies are optional and will only be obtained the sites in Germany. 
q) 
 should be completed if the subject has a history of
 at Screening. 
r) 
Dose may be increased to 3 mg/kg at Dose 4, 5, and 6 at Day 85, 113, and 141 respectively if the UCT is <12, and/ or at the discretion of the Investigator in consultation with 
the Allakos Medical Monitor, but will stay at 1 mg/kg if UCT is ≥12 and if the Investigator in consultation with the medical monitor feels that the patient has received adequate 
symptom improvement.  
s) 
During the physical exam the evaluating physician will also ask patients to rate the intensity of their atopic disease on a scale of 0–10; 0 (no symptoms) to 10 (worst possible 
symptoms). 
 
 


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Statistical Analysis Plan (Version 1.1) 
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Table 2 
Schedule of Assessments for Extended Dosing 
Description 
Screening 
Period 
Treatment Period 
Follow-up Period 
Visit 1 
Visit 2 
Visits 3-13 
Visit 14 
Ext Day -21 to  
Ext Day -14 
Ext Day 1 
 
Ext Days 29, 57, 85, 113, 141, 169, 197,  
225, 253, 281, 309 (± 2) 
Ext 365 (± 3) or ET 28 (± 3) Days 
After Last Dose 
Week -3 to -2 
Week 0 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 
Week 52 
Screening 
Baselinea/Dosing 
Dosing 
End of Study/ET 
Informed consent 
x 
 
 
 
Eligibility assessment/ 
confirmation 
x 
x 
 
 
Demographic data 
x 
 
 
 
Medical history 
x 
 
 
 
Prior CU treatment 
x 
 
 
 
Prior/concomitant medication 
x 
x 
x 
x 
Rescue medication use 
 
x 
x 
x 
Study drug administrationb 
 
x 
x 
 
Patient diary 
x 
x 
x 
x 
 
 
x 
x 
x 
UCT 
 
x 
x 
x 
 
 
x 
x 
x 
 
 
x 
x 
x 
CBC with differentiale 
 
x (pre-dose) 
x 
x 
Blood chemistry 
 
x (pre-dose) 
x (pre-dose) 
x 
Blood sample for PKf 
 
x (pre-dose) 
 
x 
Blood sample for ADAg 
 
x (pre-dose) 
x (pre-dose) 
x 
Serologyh 
x 
 
 
 
Urinalysisi 
 
x 
 
x 


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Statistical Analysis Plan (Version 1.1) 
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Allakos, Inc. 
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Table 2 
Schedule of Assessments for Extended Dosing (continued) 
Description 
Screening 
Period 
Treatment Period 
Follow-up Period 
Visit 1 
Visit 2 
Visits 3-13 
Visit 14 
Ext Day -21 to  
Ext Day -14 
Ext Day 1 
 
Ext Days 29, 57, 85, 113, 141, 169, 197,  
225, 253, 281, 309 (± 2) 
Ext 365 (± 3) or ET 28 (± 3) Days 
After Last Dose 
Week -3 to -2 
Week 0 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 
Week 52 
Screening 
Baselinea/Dosing 
Dosing 
End of Study/ET 
Urine pregnancy 
 
x 
x 
x 
Serum pregnancyj 
x 
 
 
 
Stool for ova and parasite 
x 
 
 
 
Physical examinationc 
xk 
xl 
xl 
xk 
Vital signsm 
x 
x 
x 
x 
Weight 
x 
x 
x 
x 
12-lead ECGn 
x 
 
 
x 
Adverse eventso 
 
x 
x 
x 
Table 9 Notes 
Ext: Extended 
a) Baseline is defined as up to 48 hours prior to first dose. 
b) AK002 will be administered as a single peripheral IV infusion at a dose of 0.3 mg/kg (Dose 1) on Extended Dosing Day 1. If well tolerated, the dose will be increased to 1 mg/kg 
on Extended Dosing Days 29 (Dose 2) and 57 (Dose 3). The dose will be increased to 3 mg/kg for doses 4 through 12 The Investigator in consultation with the Medical Monitor 
can up dose to 3 mg earlier than dose 4 if needed. (Extended Dosing Days 85, 113, 141, 169, 197, 225, 253, 281, and 309, respectively) if the subject has a UCT score <12, 
and/or at the discretion of the Investigator in consultation with the Allakos Medical Monitor. If the UCT score is ≥12, and if the Investigator in consultation with the Medical 
Monitor feels that the subject has received adequate symptom improvement, the subject will remain at the 1 mg/kg dose. All doses will be administered over a period of 
approximately 4 hours, although the duration of infusion and the rate at which the infusion is given may be adjusted based on Investigator discretion. Please refer to the Pharmacy 
Manual for detailed instructions on preparations, administration, and infusion rate. The Investigator in consultation with the Medical Monitor may increase the dose to 6 mg/kg 
and then to 10 mg/kg if they think that the patient has not received benefit from the lower doses. 
c) During the physical exam the evaluating physician will also ask subjects to rate the intensity of their atopic disease on a scale of 0–10; 0 (no symptoms) to 10 (worst possible 
symptoms). 
d) Subjects should complete the 
on a weekly basis. On weeks where a clinic visit is not scheduled, the 
 should be completed at home.  


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e) Blood for CBC with differential, including absolute blood eosinophil and basophil counts, will be obtained just prior to each infusion, 1 hour after the end of each infusion, and 
on Extended Dosing Day 365 (or ET). 
f) 
If possible, blood for PK analysis should be obtained from the arm not used for study drug infusion. 
g) ADA will be obtained Visits 2, 3, 5, 8 and 10. An unscheduled ADA blood sample may be obtained if an immunogenicity-related AE is suspected. 
h) Serology at screening includes hepatitis B surface antigen, hepatitis C antibody, hepatitis B core antibody, and human immunodeficiency virus. 
i) 
At screening, include urine drug screening (alcohol, amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, 
methaqualone, opiates, phencyclidine) and urine cotinine tests. 
j) 
Blood for serum pregnancy test at Screening Visit. 
k) A complete PE will be performed by either the Investigator or designee as noted in Section Error! Reference source not found.. 
l) 
A symptom-directed PE, including assessments of possible infusion site reactions, will be performed by the Investigator or designee as needed. 
m) Vital signs, including supine systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate, will be taken after the subject has been in the supine position 
for ≥5 minutes and before any blood draw. On AK002 dosing days, vital signs will be measured pre-dose and at the end of infusion. 
n) 12 lead ECGs must be recorded after 10 minutes rest in the supine position. 
o) All AEs identified, whether serious or non-serious, will be recorded in the eCRF until Day 365 (± 3) or ET 28 (± 3) days after last dose. 
 


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3.2 
Study Treatment 
3.2.1 Treatment, Dose, and Mode of Administration 
AK002 will be administered as an intravenous (IV) infusion at a dose of 0.3 mg/kg on Study Day 
1. If well tolerated, the dose will be increased to 1 mg/kg on study Day 29 and Day 57 (±2 days). 
Dose will be increased to 3 mg/ kg on Days 85, 113 and 141 if the UCT score is <12 or at the 
discretion of the Investigator in consultation with the Allakos Medical Monitor and if the 1 mg/kg 
dose was well tolerated. If the UCT score is ≥12 and if the Investigator in consultation with the 
medical monitor feels that the patient has received adequate symptom improvement, then the 
patient will continue to receive 1 mg/kg dose. The amount of AK002 to be administered will be 
calculated based on the patient’s body weight determined within 24 hours of each infusion. 
Subjects in the CholU, UF, and CSU-XOLAIR® failure cohorts at the select sites will be alllowed 
to participate in the Extended Dosing part of the study if they meet the symptom criteria below: 
subjects must have a baseline (Day 1) UCT of ≤5 and a week 22 (Day 155) UCT of ≥12 (Complete 
Response). They must have a UCT of ≤5 between Day 155 and Day 309 (i.e., within 6 months 
from last dose). All subjects that decide to receive the extended dosing will start with a dose of 
0.3 mg/kg, followed by possible dose increases to 1 mg/kg and 3 mg/kg for subsequent infusions. 
The Investigator in consultation with the Medical Monitor may increase the dose to 6 mg/kg and 
then to 10 mg/kg if they think that the patient has not received benefit from the lower doses. 
3.2.2 Duration of Study  
Total subject duration on the main study is approximately 32 weeks. 
 Screening phase: 4 weeks  
 Treatment phase: 20 weeks  
 Follow up after Treatment phase: 8 weeks  
For subjects who participate in the Extended Dosing part (select sites) of the study, their total 
extended duration is up to 52 weeks. 
 Screening: 3 weeks 
 Treatment phase: up to 44 weeks (12 infusions) 
 Follow up phase: 8 weeks 
3.3 
Methods of Assigning Subjects to Treatment Group 
All subjects will receive the same treatments. Approximately 48 subjects who meet all of the 
inclusion but none of the exclusion criteria will be enrolled and assigned a patient ID number 
(PID). The PID is comprised of study number (first 3 digits), site number (second 3 digits), disease 


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cohort (the 7th digit), and order of enrollment (the last 2 digits). The disease cohorts and the 
approximate sample sizes are defined as follows. 
1 = Cholinergic Urticaria (CholU) (n=12) 
2 = Urticaria Factitia (UF) (n=12) 
3 = Chronic Spontaneous Urticaria  Xolair Naïve (CSU-XN) (n=12) 
4 = Chronic Spontaneous Urticaria Xolair Failure (CSU-XF) (n=12) 
3.4 
Blinding 
Not applicable, as the study is open label.  
3.5 
Hypotheses  
There are no formal tests of hypotheses in this study. 
3.6 
Determination of Sample Size 
The planned sample size of approximately 48 subjects is based on common practice in early phase, 
proof-of-concept studies. 
3.7 
Changes to Analyses Planned in the Protocol 
None. 
3.8 
Efficacy Assessments 
A number of cohort-specific efficacy variables, including patient-reported outcome (PRO) 
instrument, will be assessed during the study. Subjects will be administered only with the 
instruments relevant to their condition (see  
 


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Table 3).  
 
 


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Table 3 
Patient-Reported Outcome Instruments for Efficacy Assessment 
Patient Reported Outcome Instrument 
Disease Cohort 
CholU 
UF 
CSUs 
Urticaria Control Test (UCT) (monthly) 
x 
x 
x 
Urticaria Patient Daily Diary (UPDD) 
 
 UAS7 (itch and hives) 
 
x 
 
x 
 
x 
* 
x 
x 
x 
 
x 
x 
x 
* 
If applicable. All patients who have a history of 
 at Screening will complete the 
 
 and the 
 
3.8.1 Urticaria Control Test  
The Urticaria Control Test (UCT) (Appendix B.2) is a 4-item questionnaire for assessing CU 
disease activity retrospectively over the previous 4 weeks. Each item is rated on a Likert-scale (0 
= very often to 4 = not at all) and a total score (the sum of all item scores) is calculated (range, 0 
to 16; higher scores indicate better disease control; scores ≥12 are consistent with well-controlled 
disease). The UCT total score will not be calculated when ≥1 item within the questionnaire is 
missing.  
CR, CMR, and DC for UCT are defined in Section 4. 
3.8.2 
  
 (Appendix B.3) is a 
questionnaire for the last 2 weeks. It comprises 
 each that are 
scored from 
 relating to overall functioning (including work, physical well-being, leisure and 
social activities), sleep, itching/embarrassment, mental status, swelling/eating, and limits in look 
(limitations in choice of clothing or cosmetics used due to 
). Total scores range 
from 0 to 100, with higher scores indicating worse 
. The 
 total score will not be 
calculated when >14 items within the questionnaire are missing. The 
 domain scores 
as well as the total score are calculated by using the following formula:  
∑
Item Score Reported
௡௢௡௠௜௦௦௜௡௚ ௜௧௘௠௦
 
∑
Max Possible Item Score
௡௢௡௠௜௦௦௜௡௚ ௜௧௘௠௦
ൈ100 
 
 


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3.8.3 
  
 (Appendix B.4) is a questionnaire 
for the last 2 weeks. The total score is calculated from the 
 scores. Score will be calculated 
using the formula described in Section 3.8.2.  
3.8.4 
  
 (Appendix B.5) is a 
questionnaire for the last 7 days. It comprises 
 items. Total score will be calculated and converted 
to the scale of 0-100 using the formula described in Section 3.8.2.  
3.8.5 
  
 (Appendix B.6) is a questionnaire for 
the last 4 weeks. It comprises 
 items and will be grouped into  domains. The domain and total 
scores will be calculated and converted to the scale of 0-100 using the formula described in Section 
3.8.2. 
3.8.6 
  
 (Protocol Appendix B.7) is a questionnaire for the 
last 7 days. It is a 
-item 
-specific health-related quality of life measure. An overall 
score will be calculated as well as for the following domains: Symptoms and Feelings, Daily 
Activities, Leisure, Work and School, Personal Relationships, Treatment. The minimally 
important difference of the overall 
 score for patients with CSU has been estimated to be 
. The total score is the sum of all item scores, ranging from 
 with higher score 
for more impairment. The total score will not be calculated if >1 item score is missing. 
3.8.7 Urticaria Patient Daily Diary 
All patients were provided with a Urticaria Patient Daily Diary (UPDD) to complete daily. The 
UPDD has 3 separate versions; one for CholU patients (including itch, hives and elicitors) 
(Appendix B.1.1), one for UF patients (including redness, hives, and itch) (Appendix B.1.2), and 
one for CSU patients (including itch and hives) (Appendix B.1.3). Complete Response (CR) and 
Clinically Meaningful Response (CMR) are defined in Section 4.  
3.8.8 
  
 is a 7-day sum of 
 
, where 
 
 
 respectively, and 
 is the intensity of the 
 
 (Appendix B.1.1). The symptom score 
 ranges from 
 




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 The 
 and 
 scoring systems will 
be used to assess disease activity.  
3.8.11 Skin Biopsies (optional and only in certain sites) 
The assessments of the skin biopsies will include:  
 Haematoxylin and eosin (H&E) and giemsa stains to assess the number of MCs and 
eosinophils in the skin 
 Other potential post hoc analyses to investigate the mechanism of action of AK002  
3.9 
Safety Assessments 
3.9.1 Physical Examination 
Physical examinations will be conducted at Visits 1 to 7. Clinically significant findings will be 
reported as adverse events. 
3.9.2 Vital Signs, Height and Weight 
Vital signs are measured at all visits. It includes blood pressure (BP), body temperature, heart rate, 
and respiratory rate. Height (cm) and body weight (kg) are also measured at the same visits. 
3.9.3 Laboratory Tests 
Laboratory tests will be collected at all visits. The tests include hematology, chemistry and CBC 
with differential, and urinalysis panels. Laboratory values will be categorized according to the 
appropriate laboratory reference ranges. 
3.9.4 Anti-Drug-Antibodies 
Blood will be collected for the determination of anti-drug antibodies (ADA) before the first dose 
at Visit 2 and at all the following visits. An unscheduled blood sample for ADA may be obtained 
if a related adverse event suspected of being associated with immunogenicity occurs. 
3.9.5 Electrocardiogram  
Standard 12 lead electrocardiograms (ECGs) will be recorded at all visits.  
3.9.6 Pregnancy Testing 
Serum pregnancy test (post menopause FSH) will be done only at Baseline. Urine pregnancy (for 
all women of child-bearing potential) will be done at Visits 2 to 7.  
3.9.7 Tolerability/Acceptability 
Adverse events leading to study drug discontinuation will be collected.  


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3.9.8 Medical History and Adverse Events (AEs) 
AEs that occur on/after signing Informed Consent Form (ICF) will be recorded on the AE CRF. 
Medical history and AEs will be coded for preferred term (PT) and system organ class (SOC) using 
Medical Dictionary for Regulatory Activities (MedDRA) version 21.0. AEs are evaluated by the 
investigators for seriousness, causality, and severity.  
3.9.9 Prior, Concomitant, and Prohibited Medications  
Prior medications and concomitant medications will be extracted from the Prior/Concomitant 
Medication CRF. Medications taken prior to Study Day 1 will be considered as prior medications 
and medications taken on or after Study Day 1 will be considered as concomitant medications. 
Prior and concomitant medications will be coded using WHO Drug Dictionary (WHODD March 
2018 release) for Preferred Term (PT) and Anatomical Therapeutic Chemistry (ATC) 
classification.  
Prohibited medications include, but are not limited to, 
 Omalizumab  
 H2-antihistamines  
 Routine (daily or every other day during 5 or more consecutive days) doses of systemic 
corticosteroids  
 Routine (daily or every other day during 5 or more consecutive days) doses of systemic 
hydroxychloroquine  
 Routine (daily or every other day during 5 or more consecutive days) doses of 
methotrexate, cyclosporine A, cyclophosphamide, tacrolimus and mycophenolate 
mofetil  
 Intravenous immunoglobulin G  
 Plasmapheresis  
 Regular (daily or every other day) doxepin (oral)  
 Inactive vaccination  
 Live attenuated vaccine  
 Leukotriene Antagonists 
 




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are not available, they will be imputed with last observation carried forward method (LOCF). 
The data summary will include Week 10 and Week 22 derived from the available data and 
Week 10/LOCF and Week 22/LOCF derived from the available plus the imputed data. 
5.2 
Secondary Endpoints 
1) 
Proportion of subjects with CR, CMR, and DC based on UCT (all patients) at all time points. 
Section 4 provides the definition of CR, CMR, and DC.  
2) 
Change from baseline in disease activity as assessed by UAS7 at each week in CSU patients. 
If Week 10 or Week 22 measures are not available, they will be imputed with the last non-
missing weekly UAS7 (LOCF). The data summary will include Week 10 and Week 22 
derived from the available data and Week 10/LOCF and Week 22/LOCF from the available 
plus the imputed data. 
5.3 
Exploratory Endpoints 
1) 
Change in 
 assessed by 
 
 at all post-baseline scheduled visits. 
2) 
Proportion of CSU subjects with 
 each week.  
3) 
Proportion of CSU subjects with 
 from Baseline in 
 at each week. 
4) 
Proportion of CSU subjects with 
 from Baseline in 
 at each 
week. 
5) 
Change from baseline in 
 as assessed by 
 at each week in CholU 
patients.  
6) 
Change in weekly 
 over time. 
7) 
Change in 
 at all post-baseline scheduled visits. 
For weekly assessment, missing Week 10 and Week 22 scores will be imputed with LOCF. 
5.4 
PD Endpoint 
1) 
Peripheral blood eosinophils. 
5.5 
Pharmacokinetic Endpoint 
1) 
Blood samples will be analyzed for AK002 plasma concentrations and ADA. 
5.6 
Safety Endpoints 


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1) 
Safety endpoints include physical examination 
2) 
routine safety laboratory assessments 
3) 
vital signs 
4) 
electrocardiogram (ECG) 
5) 
urine safety, and  
6) 
adverse event reporting (Visits 2–7). 
6. 
Statistical Methods 
6.1 
General Methodology  
All statistical analyses will be conducted using SAS Version 9.4 or later on the Microsoft® 
Windows Operating System.  
Continuous data will be summarized using n (number of subjects with non-missing observations), 
mean, median, standard deviation (SD), minimum value, and maximum value. Categorical data 
will be summarized using the frequency count and percentage (n, %) of subjects in each category. 
Number of subjects with non-missing values and number of subjects with missing values (e.g., 
Not Done) will be presented, where appropriate. Subjects with missing values will not contribute 
to the denominator of percentage calculations. Counts of zero in any category will be presented 
without percentage.  
All endpoints will be summarized by the individual applicable cohorts (CholU, UF, CSU-XN or 
CSU-XF). Where appropriate, the summaries will also be carried out for all 4 cohorts combined. 
Two-sided 95% confidence interval (CI) may be presented for the mean or percentage.  
The precision rules for the presentation of summary statistics will be: 
 Sample size (n, N) and number of missing responses (if displayed) – Integer 
 Mean, CI – One more decimal place than reported/collected 
 Standard deviation – Two more decimal places than reported/collected 
 Median, other percentile, minimum, maximum – Same number of decimal places as 
reported/collected 
 Ratio – two decimal places 
 Percentage – one decimal place generally, or two decimal places for <0.1% 


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The data summaries will be accompanied by individual subject data listings. All data available 
from diary, questionnaires, eCRF, and external transfer (e.g., labs) will be listed and will include 
relevant and pertinent subject information, e.g. study day. The listings will be sorted in the order 
of Cohort and unique subject ID, and assessment name and assessment date/time.  
Dates will be presented in the ISO-8601 format YYYY-MM-DD. Times will be displayed in 
24-hour clock format. Numbering for tables, figures and listings will follow ICH E3 Guidelines 
(ICH, 1996). 
6.2 
Visit Window and Unscheduled Assessments 
There is no visit window for the by visit analysis. Data will be analyzed according to the visit they 
are associated with. 
6.3 
Adjustment for Covariates 
Not applicable  
6.4 
Handling of Dropouts, Missing Data, and Data Discrepancies 
Unless specified otherwise, in deriving the total (sum) score, the total score will be derived from 
all available item scores and scaled accordingly. For example, the total score of 7 items will be 
calculated as 7× (times) average of all available items score out of the 7 intended scores. In case 
the analysis week is extended to be >7 calendar days, the total score for the week will be calculated 
as 7 x average of all available daily scores for the analysis week. Also, scores will be set to missing 
when no scores are recorded for a given 7 day period. AEs with incomplete information for start 
or stop dates (i.e., either day or month is missing) will be considered treatment-emergent (TEAE) 
unless the partial start date or the stop date confirms the AE started or ended prior to Study Day 1 
(e.g., the day of the AE start date is unknown but the month and year indicate that the AE starts 
prior to Study Day 1). AEs with missing relationship to study drug will be included in the “Related” 
category for the summary tables. AEs with missing severity will not be included in the summary 
table but will be footnoted. 
When there is incomplete information regarding dosing dates for prior and concomitant 
medication, the medication will be considered as a concomitant medication unless it contradicts 
with the stop date. For example, a medication will be considered a prior medication if the month 
and year of the end date indicates a date before Study Day 1 even though the start date could be 
missing.  
6.5 
Interim Analysis 
No interim analysis is planned.  


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6.6 
Timing of Final Analyses 
Data summary and statistical analysis will commence after all subjects have completed study 
Visit 7 (or discontinued prior to Visit 7) and the study database is cleaned and locked. 
6.7 
Multicenter Study 
This is a multicenter study. The primary analysis will have all sites pooled. When appropriate, the 
by-country summaries may be presented. Response rates will be compared between the two 
participating countries, Germany and US. 
6.8 
Multiple Comparisons/Multiplicity Adjustment 
Not applicable because no formal statistical analysis and hypothesis tests are planned. 
6.9 
Examination of Subgroups 
If sample size allows, primary and key secondary efficacy variables may be summarized by 
subgroup to explore the heterogeneity of the treatment effect across subgroups. Subgroups that 
might be considered are: 
 Gender (Male, Female) 
 Age (<30, 30 to <55, 55+) 
7. 
Statistical Analysis 
7.1 
Analysis Populations 
The population of “all enrolled subjects” consists of all subjects who signed informed consent, met 
all eligibility criteria at Screening, and having received the first dose of the study drug. 
7.1.1 Modified Intent-to-treat Population  
The modified intent-to-treat (MITT) population will consist of all subjects who are enrolled, have 
received at least one dose of study drug and have at least one post-baseline assessment for the 
primary efficacy variable UCT. 
7.1.2 Safety Population 
The safety population will consist of all subjects who signed informed consent, met all eligibility 
criteria at Screening, and having received at least one dose of study drug. 
7.1.3 Per-Protocol Population 
The Per-Protocol (PP) population may be considered for the summary. The PP population will 
consist of all subjects from the MITT-population for whom no major protocol violations adversely 
affecting the data interpretation are reported. 


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7.2 
Disposition of Subjects 
Subjects (n and %) who completed or discontinued from the study will be tabulated by cohort and 
overall using all enrolled subjects. The primary reasons for study discontinuation will be included 
in the tabulation. The primary reasons may include any of the following: 
 Subject withdrew consent 
 Lost to follow-up 
 Administrative reason 
 Adverse event  
 Investigator decision 
 Failure to follow required study procedures 
 Other 
Subject disposition will be summarized for all Enrolled Subjects, MITT, Safety, and PP 
populations. A data listing will be presented for all enrolled subjects.  
7.3 
Protocol Deviations 
Protocol deviations will include, but are not limited to 
 Non-compliance with scheduled study visit  
 Non-compliance with study treatment  
 Prohibited medications  
 Non-compliance with study inclusion or exclusion criteria  
 Non-compliance with study assessment procedures  
Protocol deviations will be reviewed and classified as major or minor based on their effect on the 
integrity of the study. Subjects with major protocol deviations will be listed. The listing will 
include a brief description of the deviation, deviation category, and if applicable, study day when 
deviation occurred along with other pertinent information. 
7.4 
Demographics and Baseline Subject Characteristics 
Descriptive statistics of subject characteristics and baseline values will be presented by cohort and 
overall using the MITT and Safety populations. 
All demographic and baseline characteristics will be included in the subject data listing. 
7.5 
Baseline Disease Characteristics 
Summaries of baseline disease characteristics will be based on the Safety population. 


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Subject incidence (n and %) of medical history (and current medical condition present before 
signing the informed consent) will be tabulated by MedDRA System Organ Class (SOC) and 
Preferred Term (PT). Subject smoking habits will also be tabulated.  
All baseline disease characteristics will be listed. 
7.6 
Treatments 
7.6.1 Treatment Compliance and Extent of Exposure 
Summaries of treatment compliance and exposure for AK002 and second generation of 
H1-antihistamine will be based on the safety population. 
Duration of 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 Treatment exposure will be summarized using descriptive statistics (n, mean, standard 
deviation, median, minimum, and maximum).  
Subjects will be tabulated with n (%) by the number of doses they received. 
7.6.2 Prior and Concomitant Medications  
Prior and concomitant medications will be tabulated separately based on the Safety Population. 
Number (n and %) of subjects taking at least one medication and the number (%) of subjects taking 
each medication at the WHODD PT level will be tabulated by ATC4 and PT. Subjects taking the 
same PT medication twice will only be counted once. 
A subject data listing will be provided to include the reported medication name, the WHODD PT, 
ATC4, indication, route, and frequency, study day, and pertinent subject information. 
A separate data listing will include subjects who received prohibited medications. 
7.7 
Efficacy Analyses 
7.7.1 Primary Efficacy Analysis 
The primary efficacy variable is the change from baseline in UCT score for each population (CSU-
XN, CSU-XF, UF, and CholU). UCT score and its change from baseline will be summarized using 
descriptive statistics by study visit (Weeks 4, 8, 10, 12, 16 for subjects enrolled under Protocol 
Amendment 2.1 and Weeks 4, 8, 12, 16, 20, 22, 24, and 28 for subjects enrolled after Protocol 


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Amendment 3). A 95% CI for the mean change will be computed. The summaries will be provided 
for each cohort.  
 Per Protocol Analysis 
This analysis will be conducted by repeating the primary analysis on the per protocol population.  
 Subgroup Analysis 
The primary efficacy analysis will be conducted for the gender and age subgroups as defined in 
Section 6.9.  
 Secondary Efficacy Analyses 
All summaries will be provided for each cohort. 
1) 
Subjects achieving UCT CR and CMR will be tabulated with % of subjects for each visit. 
Subjects achieving a maximum of 0, 1, 2, 3, or 4 responses over the 8 post-baseline visits 
(subjects enrolled under Protocol Amendment 3) will also be tabulated. A 95% CI for the % 
responses will be calculated using the binomial distribution. Subjects achieving UCT DC will 
be similarly summarized. 
2) 
Changes from baseline in UAS7 in CSU patients will be summarized similarly for each week 
the diary is collected. A 95% CI for the mean change will be reported. This analysis will also 
be carried out in the subgroup of CSU-XN patients with baseline UAS7 ≥16. 
7.7.2 Exploratory Efficacy Analyses 
1) 
Change from baseline score in 
 along 
with the visit score will be summarized descriptively with 95% confidence interval for each 
of the 4 cohorts. Where applicable, both total and domain scores will be summarized. This 
summary will be performed for all visits scheduled for assessments. 
2) 
A cumulative distribution function (CDF) plot will be created by cohort for percent of patients 
who experience a maximum of no improvement, 1-point improvement, 2-point improvement, 
up to 30-point improvement in 
 total score. A table summarizing number and percent 
of patients will also be presented. 
3) 
CSU subjects achieving 
 will be tabulated with % of subjects for each 
study week. Similarly, subjects achieving 
 ≤6 and subjects achieving ≥10 point 
decrease from baseline will be tabulated for each week. 
4) 
CSU subjects achieving ≥5 point decrease from baseline in 
 and 
 will be tabulated 
with % of subjects for each study week. 


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5) 
Change from baseline in 
 subjects will be summarized descriptively at each week. 
6) 
The daily 
 will be summarized for each subject at each 
week. The weekly average scores will be listed for all subjects. 
7) 
Changes in 
 and 
 will be summarized at 
each study visit.  
7.8 
Pharmacodynamic Analysis 
Eosinophil count from peripheral blood collected pre-dosing will be summarized by visit. 
7.9 
Pharmacokinetic Analysis 
AK002 blood concentration will be summarized by the visit the samples are collected. 
7.10 
Safety Analyses 
7.10.1 Adverse Events 
Safety assessments will be based mainly on the nature, frequency, relationship, and severity of 
adverse events (AEs). AEs will be coded by primary system organ class (SOC) and preferred term 
(PT) according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.0. The 
treatment-emergent adverse events (TEAEs) will be summarized by the number and percentage (n 
and %) of subjects in each SOC and PT. For summaries by relationship to study drug, “possibly 
related” will be combined with “related”, and “unlikely/remotely related” will be combined with 
“not related.” When multiple AEs are reported with the same preferred term, the AE of the 
strongest relation will be included in the summary by relationship, and the AE of the most severe 
grade will be included in the summary by severity table. 
The following AE incidence tables will be presented.  
 Overview of TEAEs to include 
o Number (%) of subjects who reported at least one TEAE  
o Number (%) of subjects who reported at least one treatment-related TEAE 
o Number (%) of subjects who reported at least one severe TEAE 
o Number (%) of subjects who reported at least one serious TEAE  
o Number (%) of subjects who reported at least one TEAE leading to treatment 
discontinuation  
 TEAEs by PT sorted by decreasing order of subject incidence in the combined cohort 
 TEAEs by SOC and PT sorted alphabetically  
 Study Drug-Related TEAEs by SOC and PT 
 TEAEs Grade 2+ Severity by SOC and PT 


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 TESAEs by SOC and PT 
 TEAEs leading to study drug discontinuation by SOC and PT 
Select TEAEs of pain, tenderness, erythema/redness, induration/swelling, nausea/vomiting, 
diarrhea, headache, fatigue, and myalgia will be summarized with n and % by toxicity grade. 
All AEs will be listed with onset/stop day, relationship to study drug, severity, action taken, and 
outcome. Pertinent subject information including cohort and demographics will also be included. 
Separate listings will be provided for TEAEs leading to study discontinuation and Treatment-
emergent serious AEs (TESAEs).  
7.10.2 Laboratory Test 
Laboratory data will be summarized by presenting summary statistics of raw data and change from 
baseline values (means, medians, standard deviations, ranges) at each visit for sample collection. 
For quantitative laboratory parameters, both actual values and change from baseline values will be 
summarized. 
Shift tables will be presented, in which, lab test results at baseline and post-baseline 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 the summary and shift tables will only use the planned/scheduled tests. However, both 
scheduled and unscheduled/repeat tests will be included in the data listing. 
A complete laboratory data listing, including hematology, biochemistry, urinalysis, and anti-drug 
antibodies will be provided for all subjects.  
7.10.3 ECG 
The investigator overall evaluation of normal, abnormal not clinically significant, and abnormal 
clinically significant ECG findings will be tabulated with number and % of subjects for each 
assessment visit. 
Actual and change from baseline in PR, QRS, QT, RR, QTc, and HR will be summarized with 
descriptive statistics for each assessment visit. 
Data listings will be presented for ECG parameters by visit. QTc meeting the criteria of >450 but 
≤480, >480 but ≤500 or >500 msec for the actual value, or >30 msec or >60 msec increase from 
baseline will be identified. 


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7.10.4 Vital Signs and other safety measures 
Vital signs will be summarized by presenting summary statistics of raw data and change from 
baseline values (means, medians, standard deviations, ranges) for each scheduled visit and time 
point. A data listing will include vital signs from all visits.  
Other safety assessments will be listed.  
8. 
Analysis Plan for the Extension Part of the Study 
The extension part of the study will have the same conduct and data collection as for the main part 
of the study.  A few exceptions are that the extension part (1) enrolls only patients meeting entry 
criteria from certain sites, (2) provides patients longer and flexible treatment (see 3.23.2.1), 
(3) eliminates some data collections, e.g., QoL instruments (see Table 1 and Table 2 ). The analysis 
for the extension study will virtually be the same as for the main study with some adjustment for 
the visit schedules.  No separate analysis plan will be developed for this part of the study. 
9. 
Validation  
The Clinical Operations, Data Management and Biostatistics groups at Allakos will work with 
EDC/Data Management (DM) vendor to ensure that the data collected for the study are of the 
highest quality possible. The study monitor will be responsible for reviewing and verifying the 
accuracy of the data recorded on the electronic case report forms (eCRFs) direct from source 
documents at the investigative site. The DM vendor will be responsible for performing edit checks 
and reviewing all data entered into the electronic database to identify discrepant and/or inconsistent 
values and to send queries to the clinical sites. The Investigator will be responsible for answering 
queries about discrepant data and providing electronic signatures to confirm data integrity.  
The programming of Tables, Listings and Figures (TLFs) based on the clinical data is outsourced 
to Etera Solutions (Etera). Allakos seeks to ensure the quality of the reports provided by Etera in 
the form of TLFs passing a rigorous validation process involving the following processes:  
 Derived datasets will be independently reprogrammed by a second programmer. The 
separate datasets produced by the 2 programmers must match 100%.  
 Tables will be independently reprogrammed by a second programmer and the results 
from both programs must match.  
 Figures will be checked for consistency against corresponding tables and listings, or 
independently reprogrammed if there are no corresponding tables or listings.  
 Listings will be checked for consistency against corresponding tables, figures, and 
derived datasets.  


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The entire set of TLFs will be checked for completeness and consistency prior to its delivery to 
Allakos.  
10. 
References 
International Council for Harmonisation (ICH). Guideline for industry E3, structure and content 
of clinical study reports, July 1996.  
 


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11. 
Appendices 
11.1 
Appendix A: Exclusion Criteria for the Per Protocol Populations 
11.2 
Appendix B.1.1: Urticaria Patient Daily Diary for Patient with Cholinergic Urticaria  
11.3 
Appendix B.1.2: Urticaria Patient Daily Diary for Patient with Urticaria Factitia  
11.4 
Appendix B.1.3 Urticaria Patient Daily Diary for Patients with Chronic Spontaneous 
Urticaria 
11.5 
Appendix B.2: Urticaria Control Test 
11.6 
Appendix B.3 
  
11.7 
Appendix B.4: 
 
11.8 
Appendix B.5: 
  
11.9 
Appendix B.6: 
 
11.10 Appendix B.7: 
 
11.11 Appendix B.8: 
  
11.12 Appendix C: List of Tables, Listings, and Figures 
11.13 Appendix D: Table and Listing Shells 
11.1 
Appendix A: Exclusion Criteria for the Per Protocol Populations 
The following criteria will be used to further exclude subjects from the PP population: 
 Subject received incomplete dose of study drug. 
 Subject received prohibited medication that could potentially confound 
the efficacy outcome. 
11.2 
Appendix B.1.1: Urticaria Patient Daily Diary for Patient with 
Cholinergic Urticaria  
1) 
Did you do anything today that normally triggers symptoms? 
 
No 
 
Yes, with low intensity 
 
Yes, with moderate intensity 


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 
Yes, with high intensity 
o 
What exactly? 
2) 
Did you have hives today? 
 
No 
 
Yes, with low intensity 
 
Yes, with moderate intensity 
 
Yes, with high intensity 
3) 
Did you have any itching today? 
 
No 
 
Yes, with low intensity 
 
Yes, with moderate intensity 
 
Yes, with high intensity 
4) 
How would you rate your symptoms overall today? 
 
Mild, easy to tolerate 
 
Moderate, quite noticeable, certain limitations 
 
Very intense, very noticeable, considerable limitations 
5) 
Have you taken your daily tablet of antihistamines in the last 24 hours? 
 
No ______ 
Yes _____ 
6) 
Have you taken any rescue medication in the last 24 hours? 
 
No _____ 
Yes _____ 
 
How many 
 
1 tablet, 2 tablet, 3 tablet 
7) 
Have you taken any other medications besides your regular medications in the last 24 hours (for example, pain 
tablets, cortisone, …)? 
 
No _____ 
Yes _____ 
 
How many 
 
1, 2, …, 10 
 
Medication  
 
Drug taken: Today _____ 
Yesterday ______ 
Another Date__________ 
 
Medication name ______ 
Indication _______ 
Dosage (mg) __________  
How often during the study _______ 
11.3 
Appendix B.1.2: Urticaria Patient Daily Diary for Patient with Urticaria Factitia  
1) 
Were you free of your urticaria factitia symptoms today? 
 
No ___ 
Yes ____ 
2) 
Please rate your urticaria factitia symptoms in the last 24 hours. 
 
VAS (0 means no symptoms; 10 means maximum symptoms) 


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3) 
Please rate your symptoms of redness and hives in the last 24 hours. 
 
Redness VAS (0 means no symptoms; 10 means maximum symptoms.) 
 
Hives VAS (0 means no symptoms; 10 means maximum symptoms.) 
4) 
How severe was the average and maximum itching caused by the urticaria factitia in the last 24 hours? 
 
Average itching VAS (0 means no symptoms; 10 means maximum symptoms.) 
 
Maximum itching VAS (0 means no symptoms; 10 means maximum symptoms.) 
5) 
For how many hours did you have itching caused by urticaria factitia in the last 24 hours? 
 
<3 hours ____ 
3–12 hours ____ 
>12 hours ____ 
6) 
How much did the disease impair your quality of life in the last 24 hours? 
 
Not at all ___ 
Somewhat ____ 
Much ____ 
Very much ____ 
7) 
How often did you avoid stimuli in the last 24 hours that are knows to result in symptoms? 
 
Not at all ____ 
Somewhat ____ 
To a great extent ____ 
Completely ____ 
8) 
Have you taken your daily tablet of antihistamines in the last 24 hours? 
 
No ____ 
Yes ____ 
9) 
Have you taken rescue medication in the last 24 hours? 
 
No ____ 
Yes ____ 
How many 
 
1 tablet ____ 
2 tablet ____ 
3 tablet ____ 
10) 
Have you taken any other medications besides your regular medications in the last 24 hours (for example, pain 
tablets, cortisone, ….) 
 
No ____ 
Yes ____ 
How many 
 
1 __, 2__, …., 10 __ 
 
Drug taken: Today _____, Yesterday ______, Another Date_________ 
 
Medication name ______, Indication ______, Dosage (mg) _________,  
How often during the study _______ 
11) 
Please indicate if provocation test was performed 
 
Yes ___ 
No ___ 
Indicate if hives and/or redness occurred 10 minutes after provocation, and how severe your itching was. 
 
Hives: 
Yes ___ 
No ___ 
 
Redness: 
Yes ___ 
No ___ 
 
Itching: 
NRS: 0 (no itching), 1, 2, …, 10 (max itching imaginable) 
11.4 
Appendix B.1.3 Urticaria Patient Daily Diary for Patients with Chronic 
Spontaneous Urticaria 
Diary of Symptoms 
1) 
Symptoms and medication use in the last 24 hours 


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 Hives: 
None ___ 
<20 ____ 
20–50 ______ 
>50 _____ 
 Itching: None ___ 
Mild ___ 
Moderate ___ 
Severe ___ 
2) 
Did you use the daily antihistamine tablet in the last 24 hours? 
 No ___ 
Yes ___ 
3) 
Did you use any rescue medication in the last 24 hours 
 No ___ 
Yes ___ 
 
How many 
 1 tablet ___ 2 tablets ___ 3 tablets ___ 
4) 
Did you use any other medications in the last 24 hours 
 No ___ 
Yes ___ 
 
How many 
 1 __, 2 __, …, 10 
 Drug taken: Today _____, Yesterday ______, Another Date_________ 
 Medication name ______, Indication ______, Dosage (mg) _________  
 
How often during the study _______ 
 
11.5 
Appendix B.2: Urticaria Control Test 
The Urticaria Control Test (UCT) is a simple 4-item tool. A score between 0 and 4 is assigned to 
every answer option. Subsequently, the scores for all 4 questions are summed up. Accordingly, 
the minimum and maximum UCT scores are 0 and 16, with 16 points indicating complete 
disease control. UCT questions and the score for each answer option are as follows. 
1) 
How much have you suffered from the physical symptoms of the urticaria (itch, hives 
(welts) and/or swelling) in the last four weeks? 
 
 
O very much  
O much  
O somewhat  O a little  
O not at all 
 
 
(0 points)  
(1 point)  
(2 points)  
(3 points)  
(4 points) 
2) 
How much was your quality of life affected by the urticaria in the last 4 weeks? 
 
 
O very much  
O much  
O somewhat  O a little  
O not at all 
 
 
(0 points)  
(1 point)  
(2 points)  
(3 points)  
(4 points) 


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3) 
How often was the treatment for your urticaria in the last 4 weeks not enough to control 
your urticaria symptoms? 
 
 
O very much  
O much  
O somewhat  O a little  
O not at all 
 
 
(0 points)  
(1 point)  
(2 points)  
(3 points)  
(4 points) 
4) 
Overall, how well have you had your urticaria under control in the last 4 weeks? 
 
 
O very much  
O much  
O somewhat  O a little  
O not at all 
 
 
(0 points)  
(1 point)  
(2 points)  
(3 points)  
(4 points) 
Cut off-value of ≤11 is usually recommended (<12: poorly controlled urticaria, ≥12: well 
controlled urticaria). 
Reference: www.moxie-gmbh.de 
 
 
11.6 
Appendix B.3 
  


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11.8 
Appendix B.5: 
  


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11.11 Appendix B.8: 
  


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11.12 Appendix C: List of Tables, Listings, and Figures 
 
Table No. 
Title 
Population 
 
 
 
 
 


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Listing No. 
Title 
Population 
 
 
 
 
 
Figure No. 
Title 
Population 
 
 
 
 
11.13 Appendix D: Table and Listing Shells