Conditions: Nasal Polyposis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 40
Healthy volunteers: no

Brief summary:
This is a phase 2 study to evaluate multiple doses of AK001 across 2 active doses. Pharmacodynamic activity will also be evaluated.

Detailed description:
AK001 is a monoclonal antibody which may be useful in the treatment of patients with moderate to severe nasal polyposis

Arms:
arm 1: 25 mg AK001 will be administered as multiple doses arm 2: 250 mg AK001 will be administered as multiple doses arm 3: A placebo comparator consisting of inactive excipients will be administered as multiple doses

Interventions: intervention 1: AK001 low dose intervention 2: AK001 high dose intervention 3: Placebo
Intervention descriptions: intervention 1: 25 mg AK001 will be administered as multiple doses intervention 2: 250 mg AK001 will be administered as multiple doses intervention 3: Placebo will be administered as multiple doses

Protocol document:
Prot_000.pdf: 
Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 1 of 75 
 
ALLAKOS, INC  
Clinical Research Protocol  
A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
STUDY TO EVALUATE MULTIPLE DOSES OF AK001 IN PATIENTS WITH 
MODERATE TO SEVERE NASAL POLYPOSIS 
Protocol Number: 
AK001-002 
Protocol Amendment 2.3: 27OCT2016 
Protocol Amendment 1: 
27APR2016 
Original Protocol: 
19FEB2016 
Investigational Product: 
AK001 
EudraCT Number: 
2016-000460-42 
Study Phase: 
2 
Sponsor: 
Allakos, Inc. 
75 Shoreway Road, Suite A 
San Carlos, CA 94070 
Sponsor Medical 
Monitor: 
Name:  
Alejandro Dorenbaum, MD 
Telephone: 
415-328-9115 
E-mail: 
adorenbaum@allakos.com  
 
Approval: 
 
 
 
 
Sponsor Signature (Name and Title)  
 
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.  
Alejandro Dorenbaum, MD                                                        11-11-2016


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 2 of 75 
 
PROTOCOL AGREEMENT 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the patients enrolled under my supervision and providing 
Allakos, Inc. with complete and timely information, as outlined in the protocol. It is 
understood that all information pertaining to the study will be held strictly confidential 
and that this confidentiality requirement applies to all study staff at this investigational 
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 International Conference on 
Harmonisation Good Clinical Practice guidelines and to abide by the terms of this 
protocol. 
 
Protocol Number: AK001-002 
 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate Multiple 
Doses of AK001 in Patients With Moderate to Severe Nasal Polyposis 
 
Protocol Amendment 2.3  
Date: 27OCT2016 
 
 
 
 
Investigator Signature  
 
Date 
 
Print Name and Title 
Site # 
 
 
Site Name 
 
Address 
 
 
 
Phone Number 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 3 of 75 
 
TABLE OF CONTENTS 
 
1 
BACKGROUND ........................................................................................................... 21 
1.1 
Overview of Nonclinical Studies ............................................................................. 21 
1.2 
Overview of Clinical Studies ................................................................................... 22 
2 
RATIONALE FOR STUDY AND DOSE SELECTION ........................................ 23 
3 
STUDY OBJECTIVES ................................................................................................ 24 
3.1 
Primary Objective..................................................................................................... 24 
3.2 
Secondary Objectives ............................................................................................... 24 
3.3 
Exploratory Objectives ............................................................................................ 24 
4 
STUDY DESIGN ........................................................................................................... 25 
4.1 
Study Overview ......................................................................................................... 25 
4.2 
Schedule of Events .................................................................................................... 27 
5 
CRITERIA FOR EVALUATION .............................................................................. 32 
5.1 
Safety Endpoints ....................................................................................................... 32 
5.2 
Pharmacokinetic Endpoints .................................................................................... 32 
5.3 
Efficacy Endpoints .................................................................................................... 32 
5.4 
Exploratory Biomarkers .......................................................................................... 33 
6 
PATIENT SELECTION .............................................................................................. 33 
6.1 
Study Population ....................................................................................................... 33 
6.2 
Inclusion Criteria ...................................................................................................... 33 
6.3 
Exclusion Criteria ..................................................................................................... 34 
7 
PRIOR AND CONCURRENT MEDICATIONS .................................................... 36 
7.1 
Prohibited Medications ............................................................................................ 36 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 4 of 75 
 
7.2 
Allowed Medications ................................................................................................ 36 
8 
STUDY TREATMENTS.............................................................................................. 36 
8.1 
Method of Assigning Patients to Treatment Groups ........................................... 36 
8.2 
Intranasal Steroid Adjustment ............................................................................... 37 
8.3 
Blinding....................................................................................................................... 37 
8.4 
Formulation of Test and Control Products .......................................................... 38 
8.4.1 Formulation of Test Product .................................................................................. 38 
8.4.2 Formulation of Control Product ............................................................................. 38 
8.4.3 Packaging and Labeling ......................................................................................... 38 
8.5 
Supply of Study Drug at the Site ............................................................................ 38 
8.5.1 Dosage/Dosage Regimen ....................................................................................... 38 
8.5.2 Preparation .............................................................................................................. 38 
8.5.3 Administration Instructions .................................................................................... 39 
8.6 
Supply of Study Drug at the Site ............................................................................ 39 
8.6.1 Storage ..................................................................................................................... 39 
8.7 
Study Drug Accountability ...................................................................................... 40 
8.8 
Measures of Treatment Compliance ...................................................................... 40 
9 
STUDY PROCEDURES AND GUIDELINES ......................................................... 40 
9.1 
Dietary and Lifestyle Restrictions .......................................................................... 40 
9.2 
Clinical Assessments ................................................................................................. 40 
9.2.1 Prior and Concomitant Medications ...................................................................... 40 
9.2.2 Demographics ......................................................................................................... 40 
9.2.3 Medical History ...................................................................................................... 41 
9.2.4 Physical Examination ............................................................................................. 41 
9.2.5 Vital Signs ............................................................................................................... 41 
9.2.6 Electrocardiogram ................................................................................................... 41 
9.2.7 Fecal Collection ...................................................................................................... 41 
9.2.8 Adverse Events ....................................................................................................... 41 
9.3 
Clinical Safety Laboratory Measurements ........................................................... 42 
9.3.1 Serology ................................................................................................................... 42 
9.3.2 Hematology ............................................................................................................. 42 
9.3.3 Blood Chemistry Profile ......................................................................................... 42 
9.3.4 Pregnancy and Follicle-Stimulating Hormone Tests ............................................ 42 
9.3.5 Urinalysis................................................................................................................. 43 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 5 of 75 
 
9.4 
Anti-drug Antibodies ................................................................................................ 43 
9.5 
Pharmacokinetic Measurements ............................................................................ 43 
9.6 
Efficacy Measurements ............................................................................................ 43 
9.6.1 Serum Samples for Total Immunoglobulin E ....................................................... 43 
9.6.2 Serum Samples for ImmunoCAP .......................................................................... 43 
9.6.3 Total Polyp Score.................................................................................................... 43 
9.6.4 Nasal Endoscopy ..................................................................................................... 44 
9.6.5 Computed Tomography Scan ................................................................................. 44 
9.6.6 Peak Nasal Inspiratory Flow .................................................................................. 44 
9.6.7 University of Pennsylvania Smell Identification Test™ ...................................... 44 
9.6.8 Sino-nasal Outcome Test-22 .................................................................................. 44 
9.6.9 Visual Analogue Scale and Clinical Symptoms Improvement Scale .................. 44 
9.6.10 
36-Item Short Form Health Survey ................................................................... 44 
9.6.11 
Spirometry ........................................................................................................... 44 
9.6.12 
Asthma Control Test™ ...................................................................................... 45 
9.6.13 
Exploratory Biomarkers ..................................................................................... 45 
10 
EVALUATIONS BY VISIT ........................................................................................ 45 
11 
ADVERSE EVENT REPORTING AND DOCUMENTATION ........................... 45 
11.1 
Adverse Events .......................................................................................................... 45 
11.2 
Serious Adverse Events ............................................................................................ 47 
11.3 
Procedures .................................................................................................................. 48 
11.3.1 
All Adverse Events ............................................................................................. 48 
11.3.2 
Serious Adverse Event Reporting...................................................................... 48 
11.3.3 
Pregnancy ............................................................................................................ 49 
11.4 
Anaphylaxis................................................................................................................ 49 
11.5 
Medical Monitoring .................................................................................................. 49 
12 
DISCONTINUATION AND REPLACEMENT OF PATIENTS ......................... 50 
12.1 
Early Discontinuation of Study Drug .................................................................... 50 
12.2 
Withdrawal of Patients from the Study ................................................................ 50 
12.3 
Replacement of Patients ........................................................................................... 51 
13 
PROTOCOL VIOLATIONS ...................................................................................... 51 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 6 of 75 
 
14 
DATA SAFETY MONITORING ............................................................................... 52 
14.1 
General Safety Monitoring ...................................................................................... 52 
14.2 
Data Monitoring Committee ................................................................................... 52 
14.3 
Study Stopping Rules ............................................................................................... 52 
15 
STATISTICAL METHODS AND CONSIDERATIONS....................................... 53 
15.1 
Analysis Populations ................................................................................................. 53 
15.1.1 
Safety Population ................................................................................................ 53 
15.1.2 
Pharmacokinetics Population ............................................................................. 53 
15.1.3 
Efficacy Populations........................................................................................... 53 
15.2 
Demographic and Baseline Characteristics .......................................................... 53 
15.3 
Analysis of Primary Endpoint ................................................................................ 53 
15.4 
Analysis of Secondary Endpoints ........................................................................... 54 
15.5 
Analysis of Exploratory Endpoints ........................................................................ 54 
15.6 
Safety Analysis........................................................................................................... 55 
15.7 
Sample Size and Randomization ............................................................................ 56 
15.8 
Interim Monitoring ................................................................................................... 57 
16 
DATA COLLECTION, RETENTION, AND MONITORING ............................. 57 
16.1 
Data Collection Instruments ................................................................................... 57 
16.2 
Data Management Procedures ................................................................................ 57 
16.3 
Data Quality Control and Reporting ..................................................................... 57 
16.4 
Archiving of Data ...................................................................................................... 57 
16.5 
Availability and Retention of Investigational Records ....................................... 57 
16.6 
Monitoring ................................................................................................................. 58 
16.7 
Patient Confidentiality ............................................................................................. 58 
17 
ADMINISTRATIVE, ETHICAL, AND REGULATORY CONSIDERATIONS
 
58 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 7 of 75 
 
17.1 
Protocol Amendments .............................................................................................. 59 
17.2 
Institutional Review Boards and Independent Ethics Committees .................. 59 
17.3 
Informed Consent Form .......................................................................................... 60 
17.4 
Publications ................................................................................................................ 60 
17.5 
Clinical Trial Registration ....................................................................................... 60 
18 
REFERENCES .............................................................................................................. 61 
19 
APPENDICES ............................................................................................................... 62 
19.1 
Appendix 1: Contraception Guidelines ................................................................. 63 
19.2 
Appendix 2: Polyp Scoring System ........................................................................ 64 
19.3 
Appendix 3: Lund-Mackay Scoring System ......................................................... 65 
19.4 
Appendix 4: University of Pennsylvania Smell Identification Test™ .............. 66 
19.5 
Appendix 5: Sino-nasal Outcome Test-22 ............................................................. 67 
19.6 
Appendix 6: Visual Analogue Scales for Symptoms of Rhinosinusitis and 
Clinical Symptoms Improvement Scale ............................................................................. 68 
19.7 
Appendix 7: 36-Item Short Form Health Survey ................................................ 70 
19.8 
Appendix 8: Asthma Control Test™ ..................................................................... 75 
 
LIST OF TABLES 
 
Table 1 Schedule of Events ................................................................................................ 27 
Table 2 Adverse Event Severity Grading ........................................................................ 46 
Table 3 Adverse Event Relationship to Study Drug ...................................................... 47 
 
LIST OF FIGURES 
 
Figure 1 
Study Schema .................................................................................................... 26 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 8 of 75 
 
LIST OF ABBREVIATIONS 
ACT 
Asthma Control Test™ 
ADA 
Anti-drug antibody 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ANOVA 
Analysis of variance  
ATC 
Anatomical Therapeutic Chemical  
AUC(inf) 
Area under the plasma concentration-time curve from zero hours 
to infinity 
AUC(0-t) 
Area under the plasma concentration-time curve from zero hours 
to time (t)  
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
Cmax 
Maximum plasma concentration  
CRS 
Chronic rhinosinusitis 
CRSsNP 
Chronic rhinosinusitis without nasal polyposis 
CRSwNP 
Chronic rhinosinusitis with nasal polyposis  
CT 
Computed tomography 
DMC 
Data Monitoring Committee 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
ELISA 
Enzyme-linked immunosorbent assay 
ET 
Early Termination 
EU 
European Union 
FDA 
Food and Drug Administration 
FEF 
Forced expiratory flow  
FEV1 
Forced expiratory volume in 1 second 
FSH 
Follicle-stimulating hormone 
FVC 
Forced vital capacity 
GCP 
Good Clinical Practice 
gMean 
Geometric mean 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human immunodeficiency virus 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 9 of 75 
 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IgE 
Immunoglobulin E 
IgG4 
Immunoglobulin G4 
IL 
Interleukin 
IEC 
Independent Ethics Committee 
INS 
Intranasal steroid 
IRB 
Institutional Review Board 
IXRS 
interactive voice or web response system 
IV 
Intravenous(ly) 
MAb 
Monoclonal antibody 
MC 
Mast cells 
MedDRA 
Medical Dictionary for Regulatory Activities 
PE 
Physical examination 
PGD2 
Prostaglandin D2  
PK 
Pharmacokinetic(s) 
PNIF 
Peak nasal inspiratory flow 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SF-36 
36-Item Short Form Health Survey 
Siglec 
Sialic acid-binding, immunoglobulin-like lectin 
SNOT-22 
Sino-nasal Outcome Test-22 
SOC 
System organ class 
t1/2 
Terminal elimination half-life 
TEAE 
Treatment-emergent adverse event 
TPS 
Total Polyp Score  
ULN 
Upper limit of normal 
UPSIT 
University of Pennsylvania Smell Identification Test™ 
VAS 
Visual Analogue Scale 
Vz 
Volume of distribution 
WBC 
White blood cell 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 10 of 75 
 
PROTOCOL SYNOPSIS  
TITLE 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 
Study to Evaluate Multiple Doses of AK001 in Patients With 
Moderate to Severe Nasal Polyposis 
SPONSOR 
Allakos, Inc. 
NUMBER OF SITES 
Approximately 14 investigational sites in the European Union 
and the United States 
RATIONALE 
Nasal polyps are benign edematous masses that can cause nasal 
obstruction, rhinorrhea, facial pressure, postnasal drip, and loss 
of smell. It is estimated that nasal polyps affect 1% to 4% of the 
general population with a 2:1 male to female preponderance. 
The incidence increases with age, with peak incidence between 
40 and 60 years of age. Although the etiology of nasal polyposis 
(recurrent, multiple polyps) is unknown, various comorbidities, 
such as chronic inflammation of the mucous membranes in the 
nose and paranasal sinuses, allergic rhinitis, atopy, and asthma 
have been proposed as factors in the genesis of nasal polyposis. 
Phenotypically, chronic rhinosinusitis (CRS) can be classified 
as either without nasal polyposis (CRSsNP) or with nasal 
polyposis (CRSwNP), which comprises the majority of cases of 
nasal polyposis. The more common CRSwNP is often 
characterized by eosinophilic inflammation with high levels of 
eosinophil cationic protein; interleukins (IL)-4, IL-5, and IL-13; 
and tissue immunoglobulin E (IgE). 
Treatment options for nasal polyposis range from topical and/or 
systemic corticosteroids to functional endoscopic sinus surgery. 
Patients with CRSwNP and comorbid asthma, in particular, 
have a poor therapeutic response and high polyp recurrence rate, 
and their diseases are more difficult to treat. Both diseases have 
an adverse effect on quality of life and confer a large economic 
burden.  
AK001 is a humanized immunoglobulin G4 (IgG4) monoclonal 
antibody directed against Siglec-8, a member of the 
CD33-related family of sialic acid-binding, 
immunoglobulin-like lectins (siglecs). No close homolog has 
been found in other animal or primate species apart from great 
apes and baboons. Consequently, AK001 has been studied in 
Siglec-8 humanized and transgenic mouse models and with 
human blood and tissue cells. Siglec-8 has a restricted tissue 
distribution and is expressed selectively on the surface of 
mature eosinophils, mast cells (MCs), and at lower levels on 
basophils but not in early precursors of these cell populations or 
other blood cells. Crosslinking of Siglec-8 by AK001 can 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 11 of 75 
 
induce apoptosis of eosinophils previously activated by certain 
cytokines. The antibody does not induce apoptosis in MCs, but 
inhibits histamine release and de novo synthesis of 
prostaglandin D2 (PGD2) induced by IgE receptor activation.  
High levels of eosinophils and of MCs (up to 8% of isolated 
cells) are evident in nasal polyps. Mast cells and eosinophils 
isolated from nasal polyps have been shown by flow cytometry 
to express surface Siglec-8. 
Single doses of AK001, ranging from 0.01 mg/kg to 10 mg/kg, 
were evaluated in a Phase 1, double-blind, placebo-controlled, 
dose-escalation clinical trial (AK001-001) in healthy volunteers 
and patients with atopic disease. Of the 34 subjects who were 
enrolled in the study, a total of 26 received AK001 and 8 
received placebo. In this study, AK001 was well tolerated. 
There were no infusion-related reactions or clinically relevant 
changes in vital signs, electrocardiograms (ECGs), or safety 
laboratory tests. Following infusion of AK001, values of 
markers of MC degranulation (serum tryptase and urine 
histamine/prostaglandin metabolites) remained in the normal 
ranges for all subjects. Eosinophil granule protein values 
remained in or close to the normal range in all subjects. 
Excluding the 2 subjects who received AK001 at a dose of 
0.01 mg/kg or 0.1 mg/kg for whom there were no reported 
adverse events (AEs), 4 of 8 subjects (50%) in the placebo 
group and 7 of 24 subjects (29.2%) in the AK001 groups had 
treatment-emergent adverse events (TEAE). One subject 
(12.5%) in the placebo group and 3 subjects (12.5%) in the 
AK001 groups had single incidences of upper or viral 
respiratory infection. Similarly, 1 subject (12.5%) in the placebo 
group and 3 subjects (12.5%) in the AK001 groups had single 
incidences of skin and subcutaneous tissue disorders, including 
alopecia, dermatitis, contact dermatitis, and pruritus and rash at 
the site of skin testing. Two subjects, 1 in the placebo group and 
1 in the AK001 groups, had AEs of urticaria. A single AE of 
rash that occurred on Day 2 after dosing, which was mild in 
severity and resolved without intervention, was considered 
possibly related to study drug. All other AEs were considered 
not related to study drug. No dose-limiting toxicities were 
observed, and no subject was discontinued from the study due to 
an AE. 
By reducing activated eosinophils and blocking mast-cell 
histamine and PGD2 release, AK001 may be useful in the 
treatment of patients with moderate to severe chronic nasal 
polyposis with predominant eosinophilic and MC inflammation 
and whose symptoms are resistant to treatment with intranasal 
steroids (INSs). 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 12 of 75 
 
STUDY DESIGN 
This is a Phase 2, randomized, double-blind, placebo-controlled 
study of the safety and tolerability of AK001 compared with 
placebo in patients with moderate to severe chronic nasal 
polyposis and whose symptoms are resistant to treatment with 
INSs. At least 50% of patients enrolled will have comorbid 
asthma. 
The study will comprise an up to 4-week Screening period and a 
4-week Run-in period followed by randomization and dosing 
with AK001 or placebo for 7 weeks followed by a 17-week 
observation (Post-treatment) period. There will be 10 scheduled 
study visits. The total duration of the study will be up to 
approximately 32 weeks.  
After the Screening period, approximately 70 eligible patients 
will be enrolled and enter a Run-in period of 4 weeks to achieve 
a stable regimen with a common intranasal topical steroid 
(NASONEX [mometasone furoate monohydrate] 2 sprays in 
each nostril twice a day) and discontinue any other intranasal 
topical steroid. Patients will return to the clinic at the end of the 
Run-in period prior to dosing with study drug for pre-dose 
evaluations. Patients who continue to meet the eligibility criteria 
for the study will be randomized, will continue to use 
NASONEX until the end of the study, and will also receive 
either 25 mg of AK001 (n=25), 250 mg of AK001 (n=25), or a 
corresponding placebo (n=20) on Days 0, 21, and 49. The 
randomization will be stratified based on presence or absence of 
asthma. Patients will be required to maintain their Baseline 
treatments for nasal polyposis unchanged throughout 
participation in this trial.  
Enrollment will be staggered; no more than 1 patient will be 
randomized every 4 weeks at each site. 
If there are any safety concerns, enrollment will be put on hold, 
and a safety review meeting will occur. 
A Data Monitoring Committee will be convened periodically to 
monitor the safety of patients over the course of the study.  
PRIMARY 
OBJECTIVE 
To evaluate the effect of 2 different dose levels of AK001 in 
combination with an INS versus the INS alone on the reduction 
in size of nasal polyps as evaluated by the change from Baseline 
to Week 12 after the start of treatment in Total Polyp Score 
(TPS) 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 13 of 75 
 
SECONDARY 
OBJECTIVES 
1. 
To evaluate the effect of 2 different dose levels of 
AK001 in combination with an INS versus the INS alone 
on changes from Baseline to Week 12 after the start of 
treatment in:  
a) 
Size of polyps as evaluated by Lund-Mackay 
score at selected Investigator sites by computed 
tomography (CT) scan  
b) 
Nasal airway patency as evaluated by peak nasal 
inspiratory flow (PNIF) 
c) 
Ability to smell (University of Pennsylvania 
Smell Identification Test™ [UPSIT]) 
d) 
Patient-reported symptoms of sinusitis 
(Sino-nasal Outcome Test-22 [SNOT-22] and 
Visual Analogue Scales [VASs])  
e) 
Clinical symptoms improvement scale  
f) 
Quality of life (36-Item Short Form Health 
Survey [SF-36]) 
2. 
To evaluate the time to first response in TPS 
3. 
To evaluate the change in TPS, UPSIT, and 
patient-reported symptoms of sinusitis over time 
4. 
To evaluate the safety and tolerability of 2 different dose 
levels of AK001 in combination with an INS during 
7 weeks of study drug in patients with moderate to 
severe nasal polyps and whose symptoms are resistant to 
INSs 
EXPLORATORY 
OBJECTIVES 
In all patients, to:  
1. 
Potentially explore markers of MCs and eosinophils and 
inflammatory response in blood 
In patients with comorbid asthma, to explore the effect of 
2 different dose levels of AK001 in combination with an INS 
versus the INS alone on changes from Baseline to Week 12 after 
the start of treatment in: 
1. 
TPS 
2. 
Pulmonary function (forced expiratory volume in 
1 second [FEV1], forced vital capacity [FVC], and 
forced expiratory flow [FEF]) assessed using spirometry 
3. 
Asthma-related symptoms (Asthma Control Test™ 
[ACT]) 
4. 
Use of asthma rescue therapy  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 14 of 75 
 
NUMBER OF 
PATIENTS 
Approximately 70 patients randomized to receive 25 mg of 
AK001 (n=25), 250 mg of AK001 (n=25), or a corresponding 
placebo (n=20) 
PATIENT 
SELECTION 
CRITERIA 
Inclusion Criteria: 
Patients are eligible for the study if all of the following criteria 
are met: 
1. 
Written informed consent  
2. 
Male and female patients aged ≥18 and ≤75 years at the 
time of Screening 
3. 
SNOT-22 ≥30 
4. 
At Screening, TPS of ≥5 for both nostrils with presence 
on endoscopy of nasal polyps of grade ≥2 in each nostril 
according to the polyp grading scale  
Polyp grading scale for each nostril:  
0=no nasal polyps 
1=small polyps in the middle meatus not 
reaching below the inferior border of the middle 
turbinate 
2=polyps reaching below the lower border of the 
middle turbinate 
3=large polyps reaching the lower border of the 
inferior turbinate or polyps medial to the middle 
turbinate 
4=large polyps causing complete obstruction of 
the inferior nasal cavity 
5. 
History of at least 2 of the following symptoms for more 
than 4 weeks prior to Screening: 
a) 
Anterior nasal discharge 
b) 
Posterior nasal discharge 
c) 
Nasal congestion, blockade, or 
obstruction 
d) 
Decreased sense of smell 
e) 
Facial pain or pressure 
6. 
Received continuous topical nasal steroids and/or 
leukotriene receptor antagonists for at least 8 weeks 
prior to Screening unless failure or no effect of prior 
nasal steroid or leukotriene receptor antagonist therapy 
is documented 
7. 
At randomization, received ≥80% of doses of 
NASONEX scheduled during the Run-in period  
8. 
At randomization, TPS of ≥5 for both nostrils with 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 15 of 75 
 
presence on endoscopy of nasal polyps of grade ≥2 in 
each nostril according to the polyp grading scale (see 
Inclusion Criterion #4) and despite prior INS treatment 
during the Run-in period 
9. 
Female patients must be post-menopausal for ≥1 year 
with documented follicle-stimulating hormone (FSH) 
>30 IU/L, surgically sterile (tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 
3 months, or, if of child-bearing potential, willing to use 
a highly effective method of contraception from 
Screening until at least 17 weeks after the last dose of 
the study drug is administered, which corresponds to 
approximately 5 half-lives of AK001 
10. 
Male patients with female partners of childbearing 
potential must agree to use a highly effective method of 
contraception from Screening until at least 17 weeks 
after the last dose of the study drug is administered, 
which corresponds to approximately 5 half-lives of 
AK001. 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. 
11. 
Negative Screening ova and parasite test  
12. 
No clinically significant Screening 12-lead ECG, vital 
sign, hematology, chemistry, or urinalysis findings  
13. 
Able to comply with all study procedures including 
recording scores of symptoms (i.e., anterior nasal 
discharge; posterior nasal discharge, nasal congestion, 
blockade, or obstruction; decreased sense of smell; facial 
pain or pressure) at clinic visits 
Exclusion Criteria: 
Patients are ineligible for the study if any of the following 
criteria are met: 
1. 
Use of systemic corticosteroids within 6 weeks prior to 
Screening (or 5 half-lives, whichever is longer) or 
scheduled to receive systemic corticosteroids 
2. 
Chronic use of antibiotic therapy within 3 months prior 
to Screening  
3. 
Receipt of short-term antibiotic therapy within 14 days 
prior to Screening or use of antibiotics during the 
Screening period  
4. 
Acute infection that requires antibiotic, antiviral, or 
antifungal therapy within 30 days prior to Screening 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 16 of 75 
 
5. 
Nasal surgery (including polypectomy) within 6 months 
prior to Screening 
6. 
Significant mechanical nasal airway obstruction due to 
septal deviation based on Investigator assessment 
7. 
Use of investigational drugs or participation in another 
clinical trial within 30 days or 5 half-lives, whichever is 
longer, prior to Screening 
8. 
Use of any medications that may interfere with the 
study, such as immunosuppressive drugs during the 
2 weeks before Screening, or expected to require such 
medications through Day 168 
9. 
Receipt of any live attenuated vaccines within 30 days 
or 5 half-lives, whichever is longer, prior to initiation of 
treatment in the study or expected to receive such a 
vaccine during the treatment period 
10. 
Pregnancy or lactation in women 
11. 
In patients with comorbid asthma, either of the 
following: 
a) 
A FEV1 ≤60% at Screening 
b) 
An asthma exacerbation requiring 
systemic (oral and/or parenteral) steroid 
treatment or hospitalization for 
>24 hours for treatment of asthma within 
30 days prior to Screening 
12. 
History of human immunodeficiency virus infection 
(HIV) or other severe immunosuppressive disease or 
positive HIV test at Screening 
13. 
Current diagnosis or prior history of allergic fungal 
sinusitis, cystic fibrosis, ciliary dyskinesia, Wegener’s 
Granulomatosis, or Churg-Strauss syndrome 
14. 
Current diagnosis or prior history of any other condition 
likely to present with non-eosinophilic nasal polyps  
15. 
History of hepatitis or active/chronic liver disease of any 
genesis or positive serology for hepatitis B virus (HBV) 
surface antigen, hepatitis C virus (HCV) antibody at 
Screening 
16. 
Current diagnosis or history of cancer 
17. 
A helminthic parasitic infestation, even if treated, within 
6 months prior to Screening 
18. 
History of or suspected history of cytokine release 
syndrome 
19. 
Any disease or condition (medical or surgical) which, in 
the opinion of the Investigator, might compromise the 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 17 of 75 
 
hematologic, cardiovascular, pulmonary, renal, 
endocrine, autoimmune, gastrointestinal, hepatic, 
skeletal, or central nervous systems; other conditions 
that might interfere with the absorption, distribution, 
metabolism or excretion of AK001 or would place the 
patient at increased risk (including any condition, such 
as diabetes, that would make it unsafe for the patient to 
fast as required by the study) 
20. 
Known hypersensitivity to any constituent of the product 
21. 
Legally institutionalized 
TEST PRODUCT, 
DOSE, AND ROUTE 
OF 
ADMINISTRATION 
AK001 25 mg or 250 mg, to be administered intravenously (IV) 
over approximately 1 hour on Days 0, 21, and 49 
CONTROL 
PRODUCT, DOSE 
AND ROUTE OF 
ADMINISTRATION 
Placebo, to be administered IV over approximately 1 hour on 
Days 0, 21, and 49 
DURATION OF 
PATIENT 
PARTICIPATION 
AND DURATION OF 
STUDY 
Patients will participate in the study for up to approximately 
32 weeks as follows: 
• Screening period: up to 4 weeks 
• Run-in period: 4 weeks 
• Treatment period: 7 weeks 
• Observation (Post-treatment period): 17 weeks 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 18 of 75 
 
SAFETY 
EVALUATIONS 
The safety and tolerability of 2 different dose levels of AK001 
will be assessed by determining the incidence, relationship to 
study drug, and severity of TEAEs, withdrawals due to AEs, 
and changes in vital signs, laboratory test (including anti-drug 
antibody [ADA]) findings, concomitant medication use, and 
physical examination (PE) findings. Safety results in patients 
dosed with 2 different dose levels of AK001 will be compared 
with those in patients dosed with placebo (INS alone).  
Each patient will remain at the Investigator site for a safety 
observation period of at least 8 hours following the end of each 
infusion. At the discretion of the Investigator, a longer 
monitoring period, if needed, may be implemented before the 
patient is discharged. Follow-up telephone calls will be made to 
the patient at 12 and 24 hours following the end of each 
infusion. Patients will be informed that, from discharge to the 
24 hour telephone contact, they must be accompanied by 
another adult at all times, not travel alone or travel during bad 
weather, remain close to the location of the site, and have access 
to a telephone and transportation. 
DRUG LEVEL 
EVALUATIONS 
Blood samples will be obtained at pre-defined intervals for 
assessment of serum concentrations of AK001 using a validated 
enzyme-linked immunosorbent assay (ELISA) method. 
EFFICACY 
EVALUATIONS 
The following specific efficacy evaluations will be conducted in 
all patients: 
• TPS of nasal endoscopy (blinded centralized evaluation) 
• Size of polyps as evaluated by Lund-Mackay score at 
selected Investigator sites by CT scan  
• Nasal airway patency as evaluated by PNIF 
• Ability to smell (UPSIT) 
• SNOT-22 (patient-reported symptoms) 
• VASs (patient-reported symptoms) 
• Clinical symptoms improvement scale 
• SF-36 (quality of life) 
• Blood eosinophil and basophil absolute counts 
• Potentially explore markers of MCs and eosinophils and 
inflammatory response in blood  
The following specific additional efficacy evaluations will be 
conducted in asthmatic patients: 
• TPS of nasal endoscopy (blinded centralized evaluation) 
• Pulmonary function (FEV1, FVC, and FEF) assessed 
using spirometry 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 19 of 75 
 
• ACT 
• Use of asthma rescue therapy  
STATISTICS 
Sample Size 
This study will evaluate the effect of 2 different dose levels of 
AK001 in combination with an INS versus the INS plus placebo 
on the reduction in size of nasal polyps. Assuming equal 
efficacy effect of the 2 active treatment arms, a sample size of 
approximately 70 patients (25 mg of AK001 [n=25], 250 mg of 
AK001 [n=25], and a corresponding placebo (n=20]) will 
ensure at least 80% power to detect a difference in mean nasal 
polyp scores between the placebo group (Mean= -0.3; standard 
deviation [SD] ≤1.128) and each of the AK001 groups 
(Mean= -1.9; SD ≤2.064) with an alpha of 0.05.  
Safety 
All safety analyses will be performed in the Safety Population, 
defined as all patients who were randomized and received at 
least 1 dose of the study drug. Patients will be analyzed 
according to the study drug they received. 
Safety measures including AEs, clinical safety laboratory tests 
(including ADA), vital signs, PEs, and concomitant medication 
usage) will be summarized descriptively. For quantitative 
variables, descriptive statistics including number of 
observations, mean, median, SD, and range will be provided for 
the values themselves as well as for the changes from Baseline 
by treatment group at each study visit. Qualitative variables will 
be summarized using counts and percentages in each treatment 
group at each study visit.   
Drug Level Analysis 
Pharmacokinetic analysis of AK001 will be carried out for 
patients with the serum concentration data obtained at 
pre-defined time points. 
Efficacy 
The main population for efficacy will be the Modified 
Intention-to-Treat Population, defined as all patients 
randomized who receive at least 1 dose of study drug and have a 
valid Baseline measurement and at least 1 post-baseline efficacy 
assessment. Patients will be analyzed for efficacy according to 
the group to which they were randomized.   
In addition, the primary efficacy analysis will also be performed 
for the Per-Protocol Population, defined as patients who have a 
Week 12 visit and valid efficacy measurements.  
The effect of 2 different dose levels of AK001 in combination 
with an INS versus the INS alone on the reduction in size of 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 20 of 75 
 
nasal polyps as evaluated by the change from Baseline to Week 
12 after the start of treatment in TPS will be displayed for each 
treatment group by study visit, using summary statistics 
including the number of observations, the mean, median, SD, 
and range. Each active treatment group will be compared 
separately with the placebo group for change from Baseline in 
TPS by utilizing a mixed effect repeated measures analysis of 
variance (ANOVA) model with specific contrast statement for 
Week 12 and for each comparison separately. Adjustment in 
alpha for multiple comparison will be controlled according to 
the Hochberg method, in which, if the efficacy comparison of 
the high active arm versus placebo is statistically significant at 
the 0.05 level, no penalty will be assessed to the comparison of 
low active arm versus placebo. Otherwise, the low active arm 
versus placebo will be compared at the 0.025 level. 
Additional efficacy measures will be analyzed in support of the 
primary efficacy endpoint results.  
In addition to change from Baseline in TPS, absolute values and 
percentage changes from Baseline will be analyzed separately 
using the same repeated measures model described above. A 
responder analysis will also be considered.  
Examination of treatment effect over time for TPS, UPSIT, and 
patient-reported symptoms of sinusitis (SNOT-22) will be 
examined using appropriate similar repeated measures ANOVA. 
The stratification factor, presence or absence of asthma, may be 
included in the model.  
Size of polyps as evaluated by Lund-Mackay score at selected 
Investigator sites by CT scan (the CT scans are optional and will 
only be done at Investigator sites at which appropriate and 
timely regulatory approval or authorization can be granted); 
PNIF; UPSIT; and patient-reported SNOT-22, VAS, clinical 
symptoms improvement scale, and SF-36 scores will be 
compared between each of the 2 active treatment groups and the 
placebo group using a repeated measure ANOVA with contrast 
statements for comparison at Week 12 as well as at other time 
points in the study. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 21 of 75 
 
1 
BACKGROUND 
Nasal polyps are benign edematous masses that can cause nasal obstruction, rhinorrhea, 
facial pressure, postnasal drip, and loss of smell. It is estimated that nasal polyps affect 
1% to 4% of the general population with a 2:1 male to female preponderance. The 
incidence increases with age, with peak incidence between 40 and 60 years of age.1,2 
Although the etiology of nasal polyposis (recurrent, multiple polyps)2 is unknown, various 
comorbidities, such as chronic inflammation of the mucous membranes in the nose and 
paranasal sinuses, allergic rhinitis, atopy, and asthma, have been proposed as factors in the 
genesis of nasal polyposis.3,4  
Phenotypically, chronic rhinosinusitis (CRS) can be classified as either without nasal 
polyposis (CRSsNP) or with nasal polyposis (CRSwNP), which comprises the majority of 
cases of nasal polyposis. The more common CRSwNP is characterized by eosinophilic 
inflammation with high levels of eosinophil cationic protein; interleukin (IL)-4, IL-5, and 
IL-13; and tissue immunoglobulin E (IgE).2,5  
Treatment options for nasal polyposis range from topical and/or systemic corticosteroids 
to functional endoscopic sinus surgery.5 Patients with CRSwNP and comorbid asthma, in 
particular, have a poor therapeutic response and high recurrence rate, and their diseases 
are more difficult to treat. Both diseases have an adverse effect on quality of life and 
confer a large economic burden.3  
AK001 is a humanized immunoglobulin G4 (IgG4) monoclonal antibody (MAb) directed 
against Siglec-8, a member of the CD33-related family of sialic acid-binding, 
immunoglobulin-like lectins (siglecs). No close homolog has been found in other animal 
or primate species apart from great apes and baboons. Consequently, AK001 has been 
studied in Siglec-8 humanized and transgenic mouse models and with human blood and 
tissue cells. Siglec-8 has a restricted tissue distribution and is expressed selectively on the 
surface of mature eosinophils, mast cells (MCs), and at lower levels on basophils but not 
in early precursors of these cell populations or other blood cells. Crosslinking of Siglec-8 
by AK001 can induce apoptosis of eosinophils previously activated by certain cytokines. 
The antibody does not induce apoptosis in MCs, but inhibits histamine release and de 
novo synthesis of prostaglandin D2 (PGD2) induced by IgE-receptor activation.  
High levels of eosinophils and of MCs (up to 8% of isolated cells) are evident in nasal 
polyps. Mast cells and eosinophils isolated from nasal polyps have been shown by flow 
cytometry to express surface Siglec-8.6  
By reducing activated eosinophils and blocking mast-cell histamine and PGD2 release, 
AK001 may be useful in the treatment of patients with moderate to severe chronic nasal 
polyposis with predominant eosinophilic and MC inflammation and whose symptoms are 
resistant to treatment with intranasal steroids (INSs). 
1.1 
Overview of Nonclinical Studies 
Siglec-8 is expressed only in humans and other high-level primates. However, AK001 has 
been evaluated in 2 in vivo murine models: a humanized mouse containing abundant 
human MCs and eosinophils and a Siglec-8 transgenic mouse model in which, similar to 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 22 of 75 
 
humans, functional human Siglec-8 is expressed selectively on MCs, eosinophils, and 
basophils and not in other cells.  
In the humanized mouse model engrafted with human hematopoietic stem cells in which 
human eosinophils and enhanced numbers of human MCs are present, anti-Siglec-8 
antibodies reduce IL-5–induced eosinophilia and prevent an IgE-mediated ear swelling 
response (Type I hypersensitivity reaction known as passive cutaneous anaphylaxis). 
AK001 also prevents Type 1 hypersensitivity reactions known as passive cutaneous 
anaphylaxis mediated by human MCs when administered either before or after 
sensitization of the mice with specific IgE.   
In the transgenic mouse model, AK001 binding to Siglec-8 leads to inhibition of 
IgE-mediated MC histamine release as is seen in vitro in cultured human MCs. AK001 
also inhibits IgE-mediated release of MC protease-1 from mucosal MCs in Siglec-8 
transgenic mice without significantly affecting the number of MCs in these mice, 
consistent with the inhibition of MC degranulation and lack of apoptosis shown by 
AK001 on human MCs in vitro. The in vivo demonstration of activity of AK001 in 
Siglec-8 transgenic mice is consistent with the in vitro effects on human MCs and 
eosinophils, which indicates that AK001 is pharmacologically active in this model and 
supports the use of this mouse strain as a relevant species for safety testing. 
No adverse effects on body weight or clinical signs of AK001 treatment have been 
observed in preliminary studies in Siglec-8 transgenic mice receiving up to 4 doses of 
AK001 at a 5-mg/kg dose at 3-day intervals, weekly doses of 100 mg/kg for 12 weeks, or 
a single 5-mg/kg dose in a passive systemic anaphylaxis model, a dose that is 
pharmacologically active in this model.  
For toxicity testing, Siglec-8 transgenic mice received a single intravenous (IV) bolus of 
AK001 at 2 dose levels, 50 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. At both 
dose levels, there were no adverse AK001-related effects on survival, body weights, 
clinical observations, clinical pathology, or anatomic pathology. The 
no-observed-adverse-effect level following a single IV administration of AK001 to 
transgenic mice was 100 mg/kg.  
1.2 
Overview of Clinical Studies 
AK001 was evaluated in a Phase I, double-blind, placebo-controlled, dose escalation 
clinical trial (AK001-001) in healthy volunteers and patients with atopic disease. In this 
study, subjects received single doses of AK001 ranging from 0.01 mg/kg to 10 mg/kg.  
Of the 34 subjects who were enrolled in the study, a total of 26 received AK001 and 
8 received placebo. The mean age (standard deviation [SD]) at enrollment was 
39.6 ±11.89 years (range, 22 to 62); 62% of subjects were males and 38% of subjects 
were females. The majority of subjects were White (53%), 21% of subjects were Asian, 
18% of subjects were Black or African American, and the rest of the subjects were 
Hawaiian, Pacific Islander or had races designated as “Other.” There were no major 
imbalances in age, sex, race, or ethnicity among the treatment groups. 
AK001 was well tolerated in this study. There were no infusion-related reactions. 
Following infusion of AK001, values of markers of MC degranulation (serum tryptase and 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 23 of 75 
 
urine histamine/prostaglandin metabolites) remained in the normal ranges for all subjects. 
Eosinophil granule protein values remained in or close to the normal range in all subjects. 
Excluding the 2 subjects who received AK001 at a dose of 0.01 mg/kg or of 0.1 mg/kg for 
whom there were no reported adverse events (AEs), 4 of 8 subjects (50%) in the placebo 
group and 7 of 24 subjects (29.2%) in the AK001 groups had treatment-emergent adverse 
events (TEAE). One subject (12.5%) in the placebo group and 3 subjects (12.5%) in the 
AK001 groups had single incidences of upper or viral respiratory infection. Similarly, 
1 subject (12.5%) in the placebo group and 3 subjects (12.5%) in the AK001 groups had 
single incidences of skin and subcutaneous tissue disorders, including alopecia, dermatitis, 
contact dermatitis, and pruritus and rash at the site of skin testing. Two subjects, 1 in the 
placebo group and 1 in the AK001 groups, had AEs of urticaria. A single AE of rash that 
occurred on Day 2 after dosing, which was mild in severity and resolved without 
intervention, was considered possibly related to study drug. All other AEs were 
considered not related to study drug. There were no clinically relevant changes in vital 
signs, electrocardiograms (ECGs), or safety laboratory tests, including serum chemistries, 
hematology, and urinalysis. No dose-limiting toxicities were observed, and no subject was 
discontinued from the study due to an AE. 
2 
RATIONALE FOR STUDY AND DOSE SELECTION 
The present study is a Phase 2, randomized, double-blind, placebo-controlled study of the 
safety and tolerability of 2 different dose levels of AK001 compared with placebo in 
patients with moderate to severe chronic nasal polyposis and whose symptoms are 
resistant to treatment with INSs.  
In Study AK001-001, dose-related pharmacokinetic (PK) parameters, including maximum 
plasma concentration (Cmax), area under the plasma concentration-time curve from zero 
hours to time (t) (AUC[0-t]), and area under the plasma concentration-time curve from zero 
hours to infinity (AUC[inf]), increased in a dose-proportional manner. The geometric mean 
(gMean) terminal elimination half-life (t1/2) was in the range of 20 to 27 days, which is 
typical for a MAb. The gMean clearance ranged from 4.85 to 6.86 mL/hour and did not 
appear to be a function of body weight or body mass index (BMI). The gMean volume of 
distribution (Vz) was 0.060 L/kg, also typical for a MAb.  
Siglec-8 internalization was durable and persisted as long as AK001 was present in serum. 
Siglec-8 internalization was not observed at Day 28 in the lowest dose cohort, 0.01 mg/kg, 
consistent with the undetectable levels of serum AK001 at Day 28. In all other dose 
cohorts, Siglec-8 internalization was maintained through Day 28.   
The recommended Phase 2 doses of 25 mg and 250 mg administered IV every 3 to 
4 weeks were calculated on the basis of nonclinical PK and pharmacodynamic data and on 
the PK and safety data collected in the Phase 1 study. These doses are expected to 
maintain 60% to 80% engagement and internalization of the Siglec-8 receptor; 60% to 
80% internalization of the Siglec-8 receptor is associated with substantial inhibition of 
MCs and killing of activated eosinophils in in vitro experiments. 
For additional information, please see the Investigator’s Brochure (IB). 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 24 of 75 
 
3 
STUDY OBJECTIVES 
3.1 
Primary Objective 
The primary objective is to evaluate the effect of 2 different dose levels of AK001 in 
combination with an INS versus the INS alone on the reduction in size of nasal polyps as 
evaluated by the change from Baseline to Week 12 after the start of treatment in Total 
Polyp Score (TPS) (Appendix 2 Section 19.2).  
3.2 
Secondary Objectives 
The secondary objectives are: 
1. 
To evaluate the effect of 2 different dose levels of AK001 in combination with 
an INS versus the INS alone on changes from Baseline to Week 12 after the 
start of treatment in:  
a) Size of polyps as evaluated by Lund-Mackay score (Appendix 3 Section 
19.3) at selected Investigator sites by computed tomography (CT) scan 
b) Nasal airway patency as evaluated by peak nasal inspiratory flow (PNIF) 
c) Ability to smell by the University of Pennsylvania Smell Identification 
Test™ (UPSIT) (Appendix 4 Section 19.4) 
d) Patient-reported symptoms of sinusitis (Sino-nasal Outcome Test-22 
[SNOT-22] [Appendix 5 Section 19.5] and Visual Analogue Scales [VASs] 
[Appendix 6 Section 19.6]) 
e) Clinical symptoms improvement scale3 (Appendix 6 Section 19.6) 
f) Quality of life (36-Item Short Form Health Survey [SF-36] Appendix 7 
Section 19.7) 
2. 
To evaluate the time to first response in TPS (Appendix 2 Section 19.2)  
3. 
To evaluate the change in TPS (Appendix 2 Section 19.2), UPSIT (Appendix 4 
Section 19.4), and patient-reported symptoms of sinusitis (Appendix 4 Section 
19.6) over time 
4. 
To evaluate the safety and tolerability of 2 different dose levels of AK001 in 
combination with an INS during 7 weeks of study drug in patients with 
moderate to severe nasal polyps and whose symptoms are resistant to INSs 
3.3 
Exploratory Objectives 
The exploratory objectives are to:  
1. 
Potentially explore markers of MCs and eosinophils and inflammatory 
response in blood  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 25 of 75 
 
In addition, in patients with comorbid asthma, the exploratory objectives are to explore the 
effect of 2 different dose levels of AK001 in combination with an INS versus the INS 
alone on changes from Baseline to Week 12 after the start of treatment in: 
1. 
TPS (Appendix 2 Section 19.2)  
2. 
Pulmonary function (forced expiratory volume in 1 second [FEV1], forced 
vital capacity [FVC], and forced expiratory flow [FEF]) assessed using 
spirometry 
3. 
Asthma-related symptoms (Asthma Control Test™ [ACT] Appendix 8 Section 
19.8) 
4. 
Use of asthma rescue therapy  
4 
STUDY DESIGN 
4.1 
Study Overview 
This is a Phase 2, randomized, double-blind, placebo-controlled study of the safety and 
tolerability of 2 different dose levels of AK001 compared with placebo in combination 
with an INS in patients with moderate to severe chronic nasal polyposis and whose 
symptoms are resistant to treatment with INSs. At least 50% of patients enrolled will have 
comorbid asthma. 
As presented in Figure 1, the study will comprise an up to 4-week Screening period and a 
4-week Run-in period followed by randomization and dosing with AK001 or placebo for 
7 weeks followed by a 17-week observation (Post-treatment) period. There will be 
10 scheduled study visits. The total duration of the study will be up to approximately 
32 weeks.  
After the Screening period, which will last up to 4 weeks, approximately 70 eligible 
patients will be enrolled and enter a Run-in period of 4 weeks to achieve a stable regimen 
with a common intranasal topical steroid (NASONEX; [mometasone furoate 
monohydrate] 2 sprays in each nostril twice a day) and discontinue any other intranasal 
topical steroid. Patients will return to the clinic at the end of the Run-in period prior to 
dosing with study drug for pre-dose evaluations. Patients who continue to meet the 
eligibility criteria for the study will be randomized, will continue to use NASONEX until 
the end of the study, and will also receive 25 mg of AK001 (n=25), 250 mg of AK001 
(n=25), or a corresponding placebo (n=20) on Days 0, 21, and 49. Patients will be 
required to maintain their Baseline treatments for nasal polyposis unchanged throughout 
participation in this trial. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 26 of 75 
 
Figure 1 
Study Schema 
 
 
A Data Monitoring Committee (DMC) will be convened periodically to monitor the safety 
of patients over the course of the study. Members of the DMC can request the identities of 
patients’ study drugs if needed. Additional information about the DMC can be found in 
the DMC charter.  
Enrollment will be staggered; no more than 1 patient will be randomized every 4 weeks at 
each site. 
If there are any safety concerns, enrollment will be put on hold, and a safety review 
meeting will occur. 
The schedule of the required evaluations is provided in Table 1. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
Final 
Date: 27OCT2016 
Page 27 of 75 
 
4.2 
Schedule of Events 
Table 1 
Schedule of Events 
Procedure 
Screening 
Period 
Run-in 
Period1 
Treatment Period 
Post-treatment 
Period 
Visits 
Screening 
Run-
in2 
Day 
-3 
Day 0 
Day 
1 
Day 
14 
Day 21 
Day 
22 
Day 49 
Day 
50 
Day 
84 
Day 
112 
Day 
168/ 
ET 
Days 
-56 to 
-293 
-284 
-3±2 
0  
(Pre- 
dose 
0  
1 
14±2 
21±2 
(Pre-
dose) 
21±2  
22±2 
49±2 
(Pre-
dose) 
49±2  
50±2 
84±4 
112±
4 
168±
7 
(or 
ET) 
Weeks 
-8 to -5 
-45 
-1 
0 
0 
0 
2 
3 
3 
3 
7 
7 
7 
12 
16 
24 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
assessment 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
X6 
 
 
 
 
 
 
 
 
 
 
 
 
Intranasal steroid 
adjustment7 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study drug8 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
 
 
Medical history9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete PE10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom-directed 
PE11 
 
 
 
X 
X 
 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
Follow-up telephone 
call12 
 
 
 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
Final 
Date: 27OCT2016 
Page 28 of 75 
 
Procedure 
Screening 
Period 
Run-in 
Period1 
Treatment Period 
Post-treatment 
Period 
Visits 
Screening 
Run-
in2 
Day 
-3 
Day 0 
Day 
1 
Day 
14 
Day 21 
Day 
22 
Day 49 
Day 
50 
Day 
84 
Day 
112 
Day 
168/ 
ET 
Days 
-56 to 
-293 
-284 
-3±2 
0  
(Pre- 
dose 
0  
1 
14±2 
21±2 
(Pre-
dose) 
21±2  
22±2 
49±2 
(Pre-
dose) 
49±2  
50±2 
84±4 
112±
4 
168±
7 
(or 
ET) 
Weeks 
-8 to -5 
-45 
-1 
0 
0 
0 
2 
3 
3 
3 
7 
7 
7 
12 
16 
24 
Body weight and 
height13  
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Vital signs14 
X 
 
X 
X15 
X15 
 
X 
X15 
X15 
 
X15 
X15 
 
X 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy 
test and FSH (if 
indicated)16 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
 
 
 
X 
Fecal sample for ova 
and parasites  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HBV surface 
antigen, HCV 
antibody  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology17 
X 
 
X 
 
 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
Chemistry17 
X 
 
X 
 
 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
Urinalysis 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
X 
X 
Nasal endoscopy18 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
 
CT scan  
 
 
X19 
 
 
 
 
 
 
 
 
 
 
X19 
 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
Final 
Date: 27OCT2016 
Page 29 of 75 
 
Procedure 
Screening 
Period 
Run-in 
Period1 
Treatment Period 
Post-treatment 
Period 
Visits 
Screening 
Run-
in2 
Day 
-3 
Day 0 
Day 
1 
Day 
14 
Day 21 
Day 
22 
Day 49 
Day 
50 
Day 
84 
Day 
112 
Day 
168/ 
ET 
Days 
-56 to 
-293 
-284 
-3±2 
0  
(Pre- 
dose 
0  
1 
14±2 
21±2 
(Pre-
dose) 
21±2  
22±2 
49±2 
(Pre-
dose) 
49±2  
50±2 
84±4 
112±
4 
168±
7 
(or 
ET) 
Weeks 
-8 to -5 
-45 
-1 
0 
0 
0 
2 
3 
3 
3 
7 
7 
7 
12 
16 
24 
PNIF 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
 
UPSIT 
 
 
 
X 
 
 
X 
X 
 
 
X 
 
 
X 
X 
 
SNOT-22  
X 
 
 
X 
 
 
X 
X 
 
 
X 
 
 
X 
X20 
 
VASs and clinical 
symptoms 
improvement scale21 
X 
X 
X 
X 
 
 
X 
X 
 
 
X 
 
 
X 
X20 
 
SF-36  
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
X 
 
Spirometry22 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
ACT23 
X 
 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
X20 
 
Blood for PK 
 
 
X24 
 
 
X 
X24 
 
 
X24 
 
 
X 
X 
X 
ADA25 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Blood for potential 
exploratory 
biomarker analysis26 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
 
 
Total serum IgE  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ImmunoCAP test 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
Final 
Date: 27OCT2016 
Page 30 of 75 
 
Procedure 
Screening 
Period 
Run-in 
Period1 
Treatment Period 
Post-treatment 
Period 
Visits 
Screening 
Run-
in2 
Day 
-3 
Day 0 
Day 
1 
Day 
14 
Day 21 
Day 
22 
Day 49 
Day 
50 
Day 
84 
Day 
112 
Day 
168/ 
ET 
Days 
-56 to 
-293 
-284 
-3±2 
0  
(Pre- 
dose 
0  
1 
14±2 
21±2 
(Pre-
dose) 
21±2  
22±2 
49±2 
(Pre-
dose) 
49±2  
50±2 
84±4 
112±
4 
168±
7 
(or 
ET) 
Weeks 
-8 to -5 
-45 
-1 
0 
0 
0 
2 
3 
3 
3 
7 
7 
7 
12 
16 
24 
Prior27/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
AEs 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SAEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ACT = Asthma Control Test™; ADA = anti-drug antibody; AE = adverse event; BMI = body mass index; CBC = complete blood count; CT = computed tomography; 
ECG = electrocardiogram; ET = Early Termination; FEF = forced expiratory flow; FEV1 = forced expiratory volume in 1 second; FSH = follicle-stimulating hormone; 
FVC = forced vital capacity; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IgE = immunoglobulin E; IV = intravenous; 
IXRS = interactive voice or web response system; PE = physical examination; PNIF = peak nasal inspiratory flow; PK = pharmacokinetic(s); SAE = serious adverse event; 
SF-36 = 36-Item Short Form Health Survey; SNOT-22 = Sino-nasal Outcome Test-22; TPS = Total Polyp Score; UPSIT = University of Pennsylvania Smell Identification 
Test™; VAS = Visual Analogue Scale. 
1. The Run-in period is from Day -28 (or Day -29 or Day -30) through Day -1. 
2. The Run-in clinic visit at Day -28 (or Day -29 or Day -30) may be replaced by telephone contact at the Investigator’s discretion for selected patients. If so, 
the patient will have been provided with NASONEX and copies of the VASs and clinical symptoms improvement scale at Screening and will be contacted 
by phone on Day -28 (or Day -29 or Day -30) and instructed to begin NASONEX, complete the scales, and bring the completed scales to the next (Day -3) 
clinic visit. 
3. The Screening period is from Day -56 through Day -29 (or, if Run-in starts on Day -29 or Day -30, on Day -30, or Day -31, respectively). 
4. The Run-in clinic visit or telephone contact will occur at Day -28 (or Day -29 or Day -30). The Day -28 visit may occur as soon as the day after Screening. 
Inclusion and exclusion criteria may continue to be assessed while the patient is in the Run-in period. 
5. The Run-in period will start during Week -5 if the Run-in clinic visit or telephone contact occurs at Day -29 or Day -30. 
6. Randomization will occur via IXRS after confirmation that the patient meets all inclusion and no exclusion criteria.  
7. All patients will use NASONEX (2 nasal inhalations in each nostril twice a day) and discontinue any other intranasal topical steroid from the start of the 
Run-in period through the end of the study.  


Protocol AK001-002 Amendment 2.3 
          Confidential 
Final 
Date: 27OCT2016 
Page 31 of 75 
 
8. Study Drug (AK001 or placebo) will be administered as a single IV infusion through a peripheral vein per additional specific instructions provided in the 
pharmacy manual. Each patient will remain at the Investigator site for a safety observation period of at least 8 hours following the end of each infusion. At 
the discretion of the Investigator, a longer monitoring period, if needed, before the patient is discharged may be implemented. Patients will be informed that, 
from discharge to the 24-hour telephone contact, they must be accompanied by another adult at all times, not travel alone or travel during bad weather, 
remain close to the location of the site, and have access to a telephone and transportation. If there are any safety concerns, enrollment will be put on hold.  
9. The medical history will include all relevant medical history for the 5 years before Screening (e.g., history of current disease, other pertinent respiratory 
history, and information regarding aspirin sensitivity [obtained in response to a specific question] and underlying diseases). 
10. A complete PE will be performed by either the Investigator or a qualified Sub-investigator and include the following body system or organ assessments: 
skin; head, eyes, ears, nose and throat; thyroid; lungs; cardiovascular; abdomen; extremities; lymph nodes; and a brief neurological examination. 
11. A symptom-directed PE, including assessments of possible infusion site reactions, will be performed by either the Investigator or a qualified 
Sub-investigator pre-dose (and post-dose as indicated) on Days 0, 21, and 49 and on Days 14, 84, 112, and 168 or ET. 
12. Follow-up telephone calls will be made to the patient at 12 and 24 hours following the end of each infusion.  
13. At Screening, height (in cm) and weight (in kg) will be recorded and BMI will be calculated. Pre-dose on Day 0 and on Day 112 and Day 168 or ET, weight 
(in kg) only will be recorded. 
14. Vital signs, including supine systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate, will be measured after the patient has been 
in the supine position for ≥5 minutes. 
15. On Days 0, 21 and 49, vital signs will be measured pre-dose, every 15 minutes after the start of infusion, and immediately following the end of infusion. 
16. For all female patients, blood will be obtained for a serum pregnancy test at Screening, and blood or urine is to be obtained for pregnancy tests on Day -3, 
pre-dose on Days 21 and 49, and on Day 168 or ET. Blood for FSH is to be obtained only at Screening to confirm postmenopausal status (FSH level 
>30 IU/L).  
17. Patients will refrain from alcohol and strenuous exercise (e.g., heavy lifting, weight training, aerobics) for at least 48 hours and fast overnight (8 hours) from 
food and beverages other than water prior to each blood collection for clinical safety laboratory tests as detailed in Section 9.3.3.   
18. Nasal endoscopies (blinded centralized evaluation) will be performed at Screening, on Day -3, pre-dose on Days 21 and 49, and on Days 84, and 112 or ET 
for efficacy analyses.  
19. CT scans will be performed at selected Investigator sites on Day -3 and on Day 84 or ET. CT scans are optional and will only be done at Investigator sites at 
which appropriate and timely regulatory approval or authorization can be granted. 
20. These evaluations will be performed only at ET if not obtained on Day 112. 
21. Patients will complete VASs and the clinical symptoms improvement scale at Screening; at start of Run-in; on Day -3; pre-dose on Days 0, 21, and 49; and 
on Days 14, 84, and 112 or ET. The VASs and clinical symptoms improvement scale will be completed at clinic visits; however, if the Run-in clinic visit is 
replaced by telephone contact, the patient will complete the scales at home and bring them to the next (Day -3) clinic visit. 
22. Spirometry will be performed at Screening and pre-dose on Days 21 and 49 to assess FEV1, FVC, and FEF. 
23. The ACT will be performed only in patients with comorbid asthma.  
24. Blood samples for PK on Days 0, 21, and 49 will be obtained pre-dose. 
25. Blood samples for ADA will be collected pre-dose on Day 0 and, should a related AE suspected of being associated with immunogenicity occur, post-dose, 
as well as on Day 112 and Day 168 or ET.  
26. Blood samples (5 mL serum, 5 mL plasma, and 5 mL RNAlater solution) will be obtained on Day -3, pre-dose on Days 21 and 49, and on Day 84 and stored. 
27. All prior medications, including both prescribed and over-the-counter medications, started within the 30 days before Screening will be recorded. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 32 of 75 
 
 
5 
CRITERIA FOR EVALUATION 
5.1 
Safety Endpoints 
The primary safety endpoints of this study are: 
• TEAEs 
• Withdrawals from study due to AEs 
• Vital sign findings 
• Laboratory test (including anti-drug antibody [ADA]) findings 
• Concomitant medication use 
• Physical examination (PE) findings 
5.2 
Pharmacokinetic Endpoints 
Blood samples will be obtained pre-dose on Days 0, 21, and 49 and on Days 14, 84, 112, 
and 168 for PK analyses. 
Serum concentrations of AK001 will be measured using a validated enzyme-linked 
immunosorbent assay (ELISA) method. 
5.3 
Efficacy Endpoints  
The following specific efficacy endpoints will be evaluated: 
• TPS (Appendix 2 Section 19.2) by blinded centralized evaluation of endoscopy 
• Size of polyps as evaluated by Lund-Mackay score (Appendix 3 Section 19.3) at 
selected Investigator sites by CT scan 
• Nasal airway patency as evaluated by PNIF 
• UPSIT (Appendix 4 Section 19.4) 
• SNOT-22 (patient-reported symptoms) (Appendix 5 Section 19.5) 
• VASs (patient-reported symptoms) (Appendix 6 Section 19.6) 
• Clinical symptoms improvement scale3 (Appendix 6 Section 19.6) 
• SF-36 (quality of life) (Appendix 7 Section 19.7) 
• Blood eosinophil and basophil absolute counts 
The following specific additional efficacy endpoints will be evaluated in patients with 
comorbid asthma: 
• TPS (Appendix 2 Section 19.2) by blinded centralized evaluation of endoscopy 
• Pulmonary function (FEV1, FVC, and FEF) assessed using spirometry 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 33 of 75 
 
 
• ACT (Appendix 8 Section 19.8) 
• Use of asthma rescue therapy  
5.4 
Exploratory Biomarkers 
Blood samples (5 mL serum, 5 mL plasma, 5 mL RNAlater solution) will be obtained on 
Day -3, pre-dose on Days 21and 49, and on Day 84. The samples will be stored per 
instructions in a separate manual for potential exploratory analysis of markers of MCs and 
eosinophils and of inflammatory response in blood. In the event that a patient does not 
provide consent for future analyses or storage of these samples, they will be destroyed 
according to the country-specific informed consent form (ICF). 
6 
PATIENT SELECTION 
6.1 
Study Population 
Male and female patients, aged >18 and <75 years, with moderate to severe chronic nasal 
polyposis and whose symptoms are resistant to treatment with INSs who fulfill the 
inclusion criteria and none of the exclusion criteria specified below.  
6.2 
Inclusion Criteria 
Patients are eligible for the study if all of the following criteria are met: 
1. 
Written informed consent  
2. 
Male and female patients aged ≥18 and ≤75 years at the time of Screening 
3. 
SNOT-22 (Appendix 5 Section 19.5) ≥30 
4. 
At Screening, TPS of ≥5 for both nostrils with presence on endoscopy of nasal 
polyps of grade ≥2 in each nostril according to the polyp grading scale 
(Appendix 2 Section 19.2)  
Polyp grading scale for each nostril:  
0=no nasal polyps 
1=small polyps in the middle meatus not reaching below the inferior border of 
the middle turbinate 
2=polyps reaching below the lower border of the middle turbinate 
3=large polyps reaching the lower border of the inferior turbinate or polyps 
medial to the middle turbinate 
4=large polyps causing complete obstruction of the inferior nasal cavity 
5. 
History of at least 2 of the following symptoms for 4 weeks prior to Screening: 
a) Anterior nasal discharge 
b) Posterior nasal discharge 
c) Nasal congestion, blockade, or obstruction  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 34 of 75 
 
 
d) Decreased sense of smell 
e) Facial pain or pressure 
6. 
Received continuous topical nasal steroids and/or leukotriene receptor 
antagonists for at least 8 weeks prior to Screening unless failure or no effect of 
prior nasal steroid or leukotriene receptor antagonist therapy is documented 
7. 
At randomization, received ≥80% of doses of NASONEX scheduled during the 
Run-in period  
8. 
At randomization, TPS of ≥5 for both nostrils with presence on endoscopy of 
nasal polyps of grade ≥2 in each nostril according to the polyp grading scale 
(see Inclusion Criterion #4 and Appendix 2 Section 19.2) and despite prior INS 
treatment during the Run-in period 
9. 
Female patients must be post-menopausal for ≥1 year with documented 
follicle-stimulating hormone (FSH) >30 IU/L, surgically sterile (tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 3 months, or, if of 
child-bearing potential, willing to use a highly effective method of 
contraception (Appendix 1 Section 19.1) from Screening until at least 17 weeks 
after the last dose of the study drug is administered, which corresponds to 
approximately 5 half-lives of AK001 
10. 
Male patients with female partners of childbearing potential must agree to use a 
highly effective method of contraception (Appendix 1 Section 19.1) from 
Screening until at least 17 weeks after the last dose of the study drug is 
administered, which corresponds to approximately 5 half-lives of AK001. 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. 
11. 
Negative Screening ova and parasite test  
12. 
No clinically significant Screening 12-lead ECG, vital sign, hematology, 
chemistry, or urinalysis findings  
13. 
Able to comply with all study procedures including recording scores of 
symptoms (i.e., anterior nasal discharge; posterior nasal discharge, nasal 
congestion, blockade, or obstruction; decreased sense of smell; facial pain or 
pressure) at clinic visits 
6.3 
Exclusion Criteria 
Patients are ineligible for the study if any of the following criteria are met: 
1. Use of systemic corticosteroids within 6 weeks prior to Screening (or 5 half-lives, 
whichever is longer) or scheduled to receive systemic corticosteroids 
2. Chronic use of antibiotic therapy within 3 months prior to Screening  
3. Receipt of short-term antibiotic therapy within 14 days prior to Screening or use of 
antibiotics during the Screening period 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 35 of 75 
 
 
4. Acute infection that requires antibiotic, antiviral, or antifungal therapy within 
30 days prior to Screening 
5. Nasal surgery (including polypectomy) within 6 months prior to Screening 
6. Significant mechanical nasal airway obstruction due to septal deviation based on 
Investigator assessment 
7. Use of investigational drugs or participation in another clinical trial within 30 days 
or 5 half-lives, whichever is longer, prior to Screening 
8. Use of any medications that may interfere with the study, such as 
immunosuppressive drugs during the 2 weeks before Screening, or expected to 
require such medications through Day 168 
9. Receipt of any live attenuated vaccines within 30 days or 5 half-lives, whichever is 
longer, prior to initiation of treatment in the study or expected to receive such a 
vaccine during the treatment period 
10. Pregnancy or lactation in women 
11. In patients with comorbid asthma, either of the following: 
a) A FEV1 ≤60% at Screening 
b) An asthma exacerbation requiring systemic (oral and/or parenteral) steroid 
treatment or hospitalization for >24 hours for treatment of asthma within 
30 days prior to Screening 
12. History of human immunodeficiency virus (HIV) infection or other severe 
immunosuppressive disease, or positive HIV test at Screening 
13. Current diagnosis or prior history of allergic fungal sinusitis, cystic fibrosis, ciliary 
dyskinesia, Wegener’s Granulomatosis, or Churg-Strauss syndrome 
14. Current diagnosis or prior history of any other condition likely to present with 
non-eosinophilic nasal polyps 
15. History of hepatitis or active/chronic liver disease of any genesis or positive 
serology for hepatitis B virus (HBV) surface antigen or hepatitis C virus (HCV) 
antibody at Screening 
16. Current diagnosis or history of cancer 
17. A helminthic parasitic infestation, even if treated, within 6 months prior to 
Screening 
18. History of or suspected history of cytokine release syndrome 
19. Any disease or condition (medical or surgical) which, in the opinion of the 
Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, 
endocrine, autoimmune, gastrointestinal, hepatic, skeletal, or central nervous 
system; other conditions that might interfere with the absorption, distribution, 
metabolism or excretion of AK001 or would place the patient at increased risk 
(including any condition, such as diabetes, that would make it unsafe for the patient 
to fast as required by the study) 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 36 of 75 
 
 
20. Known hypersensitivity to any constituent of the product 
21. Legally institutionalized  
7 
PRIOR AND CONCURRENT MEDICATIONS 
Prior and concomitant medications include both prescribed and over-the-counter 
medications. The Investigator is to record the use of all prior medications started within the 
30 days before Screening and of all concomitant medications during the study in the 
Electronic Case Report Form (eCRF). Continuous topical nasal steroids and/or leukotriene 
receptor antagonists are to have been received for at least 8 weeks prior to Screening 
(Inclusion Criterion #6). 
No medications as specified in Exclusion Criteria #1, #2, #3, #4, #7, #8, #9, and #11b are 
to have been received. On Day 0 before randomization, investigational site personnel 
should ensure that patients meet none of the exclusion criteria pertaining to medications. 
Patients should be advised against taking any new medication, both prescribed and over the 
counter, without consulting the Investigator, unless the new medication is required for 
emergency use. 
7.1 
Prohibited Medications  
All medications taken during the conduct of this study must be documented on the eCRF. 
The use of immunosuppressive drugs is prohibited during the 2 weeks before Screening 
and systemic corticosteroids is prohibited during the 6 weeks before Screening (or 
5 half-lives, whichever is longer) and during the study, except as necessary to treat AEs 
under the direction of the Investigator.  
7.2 
Allowed Medications 
Medications (other than those that are prohibited [Section 7.1]), such as asthma 
medications, are allowed during the study and, unless dose changes are required due to 
unforeseen medical necessities, doses are to remain stable. All medication use will be 
documented in the eCRF. 
If a patient experiences an infusion-related reaction that is considered mild to moderate 
(e.g., itching or a localized rash), an antihistamine, acetaminophen, and, if needed, a 
glucocorticoid (e.g., IV methylprednisolone 125 mg) may be administered. If a patient 
experiences signs or symptoms of anaphylaxis, the patient will be treated with 
standard-of-care medications, such as diphenhydramine, acetaminophen, 
methylprednisolone, epinephrine, and other supportive measures along with cessation of 
the infusion.   
8 
STUDY TREATMENTS 
8.1 
Method of Assigning Patients to Treatment Groups 
Each patient who provides informed consent will be assigned a Screening number that 
uniquely identifies him or her.  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 37 of 75 
 
 
Approximately 70 patients who complete the Screening and Run-in periods of the study 
will be randomized in a double-blind fashion to receive 1 of the following treatments: 
• Arm A: AK001 25 mg (n=25) 
• Arm B: AK001 250 mg (n=25) 
• Arm C: Matching placebo (n=20) 
The randomization will be stratified by the presence of comorbid asthma. Enrollment will 
be staggered; no more than 1 patient will be randomized every 4 weeks at each site. 
Randomization will occur on Day 0 via interactive voice or web response system (IXRS) 
after confirmation that the patient meets all inclusion and no exclusion criteria. An 
unblinded non-study statistician will produce the randomization schedule with a fixed 
reproducible random seed for use in the IXRS.  
8.2 
Intranasal Steroid Adjustment 
After the patient has completed the Screening procedures, the patient will enter a 4-week 
Run-in period to achieve a stable regimen with a common intranasal topical steroid 
(NASONEX [mometasone furoate monohydrate]) and discontinue any other intranasal 
topical steroids. The Day -28 visit may occur as soon as the day after Screening. Patients 
will be instructed to self-administer 2 NASONEX nasal inhalations in each nostril twice a 
day from the start of the Run-in period through the end of the study. The patient will record 
the date and time of each dose taken in a dosing diary. Inclusion and exclusion criteria may 
continue to be assessed while the patient is in the Run-in period. 
Patients must have received ≥80% of doses of NASONEX scheduled for the Run-in period 
to be randomized.  
8.3 
Blinding 
The identity of test and control treatments will not be known to Investigators, research 
staff, patients, or the study monitor. Members of the DMC can request the identity of 
treatments if needed. The following study procedures will be in place to ensure 
double-blind administration of study treatments: 
• Access to the randomization codes will be strictly controlled via IXRS  
• Throughout the study, the blind should remain unbroken except and only for an 
emergency when knowledge of the patient’s study medication is necessary for 
further patient management or if required for regulatory reporting. When possible, 
the Investigator should discuss the emergency with the Medical Monitor prior to 
unblinding.  
• The prepared test and control IV infusion solutions will be identical in appearance 
Other than under the conditions described above, the study blind will be broken on 
completion of the study after the study database has been locked. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 38 of 75 
 
 
8.4 
Formulation of Test and Control Products 
8.4.1 Formulation of Test Product 
AK001 is a humanized IgG4 MAb directed against Siglec-8. AK001 Drug Product is 
supplied as a sterile liquid in a single-use 10R glass vial with a fill volume of not less than 
10 mL. The product is stored at 2 to 8°C. The AK001 formulation is 15 ±1.5 mg/mL 
AK001 in 125 mM arginine, 80 mM sodium chloride, 20 mM succinate and 0.025% 
polysorbate 80 (w/v), pH 6.0, in sterile water for injection. 
AK001 is administered by IV infusion. Dose preparation and administration details are 
provided in the study pharmacy manual. 
8.4.2 Formulation of Control Product 
The placebo is supplied as a sterile liquid in a single-use 10R glass vial with a fill volume 
of not less than 10 mL. The placebo contains 125 mM arginine, 80 mM sodium chloride, 
20 mM succinate and 0.025% polysorbate 80 (w/v), pH 6.0, in sterile water for injection. 
The vial is indistinguishable from the AK001 active product. The placebo is stored at 2 to 
8°C. 
8.4.3 Packaging and Labeling 
AK001 Drug Product and placebo are supplied as a sterile liquid in a single-use 10R glass 
vials with a fill volume of at least 10 mL. Each vial will be labeled with information 
required by the Food and Drug Administration (FDA) and according to pertinent European 
Union (EU) and national regulations, as appropriate for the country in which the study drug 
is being used. 
Each carton (kit) of study drug will be labeled with the required FDA investigational use 
statement, a lot number, name of the Sponsor, and directions for storage.  
8.5 
Supply of Study Drug at the Site 
The Sponsor (or designee) will ship study drug to the investigational sites. The initial 
shipment will occur after site activation (i.e., all required regulatory documentation has 
been received by the Sponsor and a contract has been executed).  
8.5.1 Dosage/Dosage Regimen 
AK001 25 mg and 250 mg and placebo will each be administered as a single IV infusion of 
over approximately 1 hour through a peripheral vein. 
8.5.2 Preparation 
Using the IXRS, the unblinded study pharmacist will prepare the AK001 or placebo for IV 
administration to each patient on Days 0, 21, and 49. Preparation of individual solutions for 
IV administration will be performed at the investigational site by the designated unblinded 
study pharmacist using the randomization code provided. Each vial is assigned a kit 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 39 of 75 
 
 
number that can be associated with a treatment assignment in the system by a list accessible 
to an unblinded monitor, independent of the study. The diluted IV solution container will 
be identified with the patient identifier, but will not indicate the treatment assignment. 
Appropriate aseptic technique will be used, and the drug will be prepared according to the 
pharmacy manual for AK001.  
8.5.3 Administration Instructions  
Specific instructions for study drug administration are detailed in the pharmacy manual. In 
general, AK001 and placebo will be infused over approximately 1 hour through a 
peripheral vein. The IV will be kept open before and after the infusion with sufficient 
quantities of 0.9% saline to assure it remains patent.  
Each patient will remain at the Investigator site for a safety observation period of at least 
8 hours following the end of each infusion. At the discretion of the Investigator, a longer 
monitoring period, if needed, before the patient is discharged, may be implemented. 
Follow-up telephone calls will be made to the patient at 12 and 24 hours following the end 
of each infusion. Patients will be informed that, from discharge to the 24-hour telephone 
contact, they must be accompanied by another adult at all times, not travel alone or travel 
during bad weather, remain close to the location of the site, and have access to a telephone 
and transportation. If there are any safety concerns, enrollment will be put on hold, and a 
safety review meeting will occur.  
The IV infusion may be interrupted for 5 to 30 minutes and the rate may be reduced and 
gradually increased in 15-minute intervals if a patient experiences infusion-related 
reactions. Acetaminophen and, if needed, a glucocorticoid (e.g., 125 mg 
methylprednisolone IV) may be administered to the patient if the patient experiences 
reactions that is considered mild to moderate (e.g., itching or a localized rash). If a patient 
experiences signs or symptoms of anaphylaxis, the patient will be treated with 
standard-of-care medications, such as diphenhydramine, acetaminophen, 
methylprednisolone, epinephrine, and other supportive measures along with cessation of 
the infusion. Administration will be discontinued if, in the opinion of the Investigator, the 
infusion cannot be restarted after 30 minutes for safety reasons. 
8.6 
Supply of Study Drug at the Site 
AK001 (15 mg/mL) and placebo will be provided by the Sponsor in 10R single-use vials. 
Study drug may be prepared on the morning of Day 0. Any patient who is randomized but 
not treated will be replaced by another patient and new study drug will be prepared for the 
alternate patient.  
8.6.1 Storage 
AK001 and placebo will be stored by the investigational site at 2ºC to 8ºC under lock at 
each site’s pharmacy room, 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 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 40 of 75 
 
 
below this range, this will be reported to the Sponsor or designee and considered a 
deviation, and study drug should be quarantined until further notice from Sponsor.   
8.7 
Study Drug Accountability 
The unblinded study pharmacist will keep accurate and current accounting of the 
preparation and dose of study drug for each patient, with sources and quantities of study 
drug received, quantities of study drug dispensed for and used by each individual patient 
specified, and quantities of study drug returned, if applicable. A drug dispensing and 
accountability log will be maintained by the unblinded study pharmacist.  
8.8 
Measures of Treatment Compliance 
The study drug will be administered under supervision of the Investigator or designee. The 
calendar date and 24-hour clock times each infusion is initiated and concluded and, as 
necessary, interrupted and resumed will be documented in the eCRF.  
9 
STUDY PROCEDURES AND GUIDELINES 
A Schedule of Events depicting the required procedures to be performed for the duration of 
the study is provided in Table 1. 
Prior to conducting any study-related activities, the ICF and any other required 
country-specific documents must be signed and dated by the patient. 
9.1 
Dietary and Lifestyle Restrictions 
Patients will refrain from alcohol and strenuous exercise (e.g., heavy lifting, weight 
training, aerobics) for at least 48 hours prior to each blood collection for clinical safety 
laboratory tests. 
Patients will be required to fast overnight (8 hours) from food and beverages other than 
water before blood is drawn for clinical safety laboratory tests. The duration of the fast 
should be no longer than the typical overnight sleeping period for the patient. 
9.2 
Clinical Assessments 
9.2.1 Prior and Concomitant Medications 
All prior medication and therapies received between 30 days before Screening and start of 
study drug will be documented at Screening and at Days -3, and pre-dose on Day 0. 
All concomitant medication and concurrent therapies will be documented post-dose on 
Day 0 and on Days 14, 21, 49, 84, 112, and 168 or at Early Termination (ET). Dose, route, 
unit, frequency of administration, indication for administration, and dates of each 
medication will be recorded.  
9.2.2 Demographics  
Demographic information (date of birth, gender, and race) will be recorded at Screening. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 41 of 75 
 
 
9.2.3 Medical History  
A medical history will be obtained at Screening and include all relevant medical history 
information (e.g., history of current disease, other pertinent respiratory system history, 
information regarding aspirin sensitivity [obtained in response to specific question(s) about 
aspirin sensitivity], and underlying diseases) for the 5 years before Screening. 
9.2.4 Physical Examination 
A complete PE will be performed by either the Principal Investigator or a qualified 
Sub-investigator at Screening. A complete PE will include the following body system or 
organ assessments: skin; head, eyes, ears, nose, and throat (HEENT); thyroid; lungs; 
cardiovascular system; abdomen; extremities; lymph nodes; and a brief neurological 
examination. Height (in cm) and weight (in kg) will be measured at Screening, and BMI 
will be calculated. Weight only will be measured on Day 0, Day 112, and Day 168 or ET. 
A symptom-directed PE, including assessments of possible infusion site reactions, will be 
performed by either the Investigator or a qualified Sub-investigator pre-dose (and post-dose 
as indicated) on Days 0, 21, and 49 and on Days 14, 84, 112, and 168 or ET. New abnormal 
PE findings must be documented and will be followed by the Investigator or qualified 
Sub-investigator at the next scheduled visit. 
9.2.5 Vital Signs 
Body temperature, supine systolic and diastolic blood pressure, pulse, and respiratory rate 
will be measured at Screening and on Days -3, 0, 14, 21, 49, 84, 112, and 168 or ET. On 
Days 0, 21, and 49, vital signs will be measured pre-dose, every 15 minutes after the start 
of infusion, and immediately following the end of infusion. All vital signs will be measured 
after the patient has been in the supine position for ≥5 minutes.  
9.2.6 Electrocardiogram 
A 12-lead ECG will be performed at Screening.  
9.2.7 Fecal Collection  
Fecal samples will be collected at Screening for ova and parasite tests.  
9.2.8 Adverse Events 
Information regarding AEs will be obtained from the time of the first study drug 
administration until completion of the last study-related procedure (Day 168 or ET). 
Information regarding serious adverse events (SAEs) will be obtained from the time the 
patient signs an ICF until completion of the last study-related procedure (Day 168 or ET). 
Duration (start and stop dates and times), severity, outcome, treatment, and relation to 
study drug will be recorded on the eCRF. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 42 of 75 
 
 
9.3 
Clinical Safety Laboratory Measurements  
Blood and urine samples will be obtained for clinical safety laboratory tests (hematology, 
chemistries, and urinalyses) and for ADA as specified in Table 1 and Sections 9.3.2, 9.3.3, 
and 9.3.5. Blood for clinical safety laboratory tests will be collected following an overnight 
fast (8 hours) from food and beverages other than water. The duration of the fast should be 
no longer than the typical overnight sleeping period for the patient. 
Certified laboratories will be used to process and provide results for the clinical safety 
laboratory tests. The Baseline laboratory test result will be defined as the last measurement 
prior to the first infusion of study drug. 
For any laboratory test value outside the reference range that the Investigator considers 
clinically significant, the Investigator will: 
• Repeat the test to verify the out-of-range value 
• Follow the out-of-range value to a satisfactory clinical resolution 
The Investigator will record as an AE any laboratory test value that (1) is confirmed and the 
Investigator considers clinically significant, (2) that requires a patient to be discontinued 
from the study, or (3) that requires a patient to receive treatment. 
9.3.1 Serology 
Blood will be obtained at Screening for HIV, HBV surface antigen, and HCV antibody 
testing. 
9.3.2 Hematology 
Blood will be obtained at Screening; on Day -3; pre-dose on Days 21 and 49, and on 
Days 14, 84, 112, and 168 or ET for a complete blood count (CBC) with differential: 
hemoglobin, hematocrit, red blood cell count, white blood cell (WBC) count, WBC 
differential, and platelet count. 
9.3.3 Blood Chemistry Profile 
Blood will be obtained at Screening; on Day -3; pre-dose on Days 21 and 49; and on 
Days 14, 84, 112, and 168 or ET for determination of serum sodium, potassium, chloride, 
bicarbonate, glucose, blood urea nitrogen, creatinine, creatinine kinase, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total 
bilirubin, direct bilirubin, gamma-glutamyl transferase, albumin, and lactate 
dehydrogenase.  
9.3.4 Pregnancy and Follicle-Stimulating Hormone Tests 
For all female patients, blood will be obtained for a serum pregnancy test at Screening, and 
blood or urine is to be obtained for pregnancy tests on Day -3, pre-dose on Days 21 and 49, 
and on Day 168 or ET. Blood for FSH is to be obtained only at Screening to confirm 
postmenopausal status (FSH level >30 IU/L).  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 43 of 75 
 
 
9.3.5 Urinalysis 
Urine will be obtained at Screening; pre-dose on Days -3 and 49; and on Days 14, 84, 112, 
and 168 or ET for determination of color, specific gravity, pH, protein, glucose, ketones, 
and blood. 
9.4 
Anti-drug Antibodies 
Blood will be collected for determination of ADA pre-dose on Day 0 and, should a related 
AE suspected of being associated with immunogenicity occur, post-dose, and on Days 112 
and 168 or ET. 
9.5 
Pharmacokinetic Measurements 
Blood samples for serum concentrations of AK001 will be obtained pre-dose on Days 0, 
21, and 49 and on Days 14, 84, 112, and 168 or ET for PK analyses. AK001 concentrations 
will be determined by a central laboratory using an ELISA method. Specific information on 
PK collection, processing, storage, and shipment will be provided in a separate manual. 
9.6 
Efficacy Measurements 
Specific information on the collection, processing storage, and shipment of samples will be 
provided in a separate manual. 
9.6.1 Serum Samples for Total Immunoglobulin E 
Blood will be collected for the testing of total IgE on Day -3.  
9.6.2 Serum Samples for ImmunoCAP  
Blood will be collected for the determination of allergen specific IgE on Day -3. Allergens 
to be used in testing are house dust mites (Dermatophagoides farina and 
Dermatophagoides pteronyssinus), birch, timothy grass (Phleum pretense), mugwort 
(Artemisia vulgarism), cat, orchard, and ragweed. 
9.6.3 Total Polyp Score 
Polyps will be evaluated in each nostril by means of nasal endoscopy and graded based on 
polyp size, resulting in scores of 0 to 4 (Appendix 2 Section 19.2). The TPS is the sum of 
the left and right nostril scores. The TPS values for efficacy analyses will be determined 
from blinded central evaluations of nasal endoscopies performed at Screening, on Day -3, 
pre-dose on Days 21 and 49, and on Days 84, and 112 or ET. Videos of the endoscopies 
will be evaluated by independent blinded reviewer. The primary endpoint of this study is 
the reduction in TPS values from Baseline to Week 12 after the start of treatment.  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 44 of 75 
 
 
9.6.4 Nasal Endoscopy 
Nasal endoscopies (blinded centralized evaluation) will be performed at Screening, on 
Day -3, pre-dose on Days 21 and 49, and on Days 84 and 112 or ET for efficacy analyses. 
Videos of the endoscopy will be evaluated by independent blinded reviewer. 
9.6.5 Computed Tomography Scan 
At selected Investigator sites, CT scans will be performed at Days -3 and 84 or ET to assess 
size of nasal polyps based on Lund-Mackay score (Appendix 3 Section 19.3). The CT 
scans are optional and will only be done at Investigator sites at which appropriate and 
timely regulatory approval or authorization can be granted. 
9.6.6 Peak Nasal Inspiratory Flow 
Peak nasal inspiratory flow will be performed pre-dose on Days 0 and 21 and on Day 84 
and 112 or ET to assess the extent of nasal airway patency. 
9.6.7 University of Pennsylvania Smell Identification Test™ 
The UPSIT (Appendix 4 Section 19.4) will be self-administered by patients pre-dose on 
Days 0, 21, and 49 and on Days 14, 84, and 112 or ET to assess ability to smell.  
9.6.8 Sino-nasal Outcome Test-22 
The SNOT-22 (Appendix 5 Section 19.5) will be completed by patients at Screening; 
pre-dose on Days 0, 21, and 49, and on Days 14, 84, and 112 or ET to assess rhinosinusitis 
symptoms.  
9.6.9 Visual Analogue Scale and Clinical Symptoms Improvement Scale 
Visual analogue scales and the clinical symptoms improvement scale3 (Appendix 6 Section 
19.6) will be completed by patients at Screening; at start of Run-in; on Day -3, pre-dose on 
Days 0, 21, and 49; and on Days 14, 84, and 112 or ET to assess rhinosinusitis symptom 
severity. The VASs and clinical symptoms improvement scale3 will be completed at clinic 
visits; however, if the Run-in clinic visit is replaced by telephone contact, the patient will 
complete the scales at home and bring them to the next (Day -3) clinic visit. 
9.6.10 36-Item Short Form Health Survey  
The SF-36 (Appendix 7 Section 19.7) will be completed by patients pre-dose on Days 0, 
21, and 49 and on Days 84 and 112 or ET to assess quality of life. 
9.6.11 Spirometry 
Spirometry will be performed at Screening and pre-dose on Days 21 and 49 to assess 
FEV1, FVC, and FEF. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 45 of 75 
 
 
9.6.12 Asthma Control Test™ 
In patients with comorbid asthma, the ACT (Appendix 8 Section 19.8) will be completed 
by patients at Screening; pre-dose on Days 0, 21, and 49; and on Days 84, and 112 or ET to 
assess the frequency of shortness of breath and general asthma symptoms, use of asthma 
rescue medications, the effect of asthma on daily functioning, and overall asthma control. 
9.6.13 Exploratory Biomarkers 
Blood samples (5 mL serum, 5 mL plasma, and 5 mL RNAlater solution) will be obtained 
on Day -3, pre-dose on Days 21 and 49, and on Day 84 and stored for potential analyses of 
markers of MCs and eosinophils and of inflammatory response in blood. In the event that a 
patient does not provide consent for future analyses or storage of these samples, they will 
be destroyed according to the country-specific ICF. 
Specific details of sampling and sample storage and processing procedures will be 
documented in a separate manual to be filed in the trial master file. The results of the 
analyses will be reported in an appendix to the clinical study report. 
10 
EVALUATIONS BY VISIT 
Evaluations and procedures by visit are depicted in Table 1. 
11 ADVERSE EVENT REPORTING AND DOCUMENTATION 
11.1 
Adverse Events 
In accordance with 21 Code of Federal Regulations (CFR) 312.32(b), 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 frequency in the current 
IB or of greater severity or frequency than expected based on the information in the IB. 
AE Recording: 
At each evaluation, the Investigator will determine whether any AEs have occurred. The 
assessment of an AE will be done pursuant to definitions set forth by International 
Conference on Harmonisation (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).  
The Investigator or designee will be notified if any patient experiences an AE. Any initial 
information discovered by the Investigator or designee (i.e., complaint[s] and known 
start/end dates and times) will be documented on the patient’s AE form. The Investigator or 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 46 of 75 
 
 
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. 
In the event that the Investigator is not available, the assigned staff will page the 
Sub-investigator on‐call and have the AE documented by telephone contact. The 
medication dispensed will be documented on an Investigator order form, and the phone call 
will be documented on the same form (if applicable). The patient will be seen by the 
Investigator as soon as possible. 
Action taken will be categorized as “none,” “study drug discontinued,” “dose modified,” 
“required concomitant medication,” “required procedure,” 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.”  
AE Severity: 
Adverse events are to be recorded on the AE page of the eCRF. Severity will be graded 
according to the definitions, based on the Common Terminology Criteria for Adverse 
Events, Version 4.0,7 listed in Table 2. It should be pointed out that the term “severe” is a 
measure of intensity and that a severe AE is not necessarily serious. 
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., having distinct onset dates). 
Table 2 
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 for which the outcome is death. 
 
Adverse Event Relationship to Study Drug: 
The relationship of an AE to the study drug should be assessed using the following the 
guidelines in Table 3. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 47 of 75 
 
 
Table 3 
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. 
 
11.2 
Serious Adverse Events  
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. 
• 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 require intervention to prevent 1 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. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 48 of 75 
 
 
11.3 
Procedures 
11.3.1 All Adverse Events 
In the event that a patient completes a study with an ongoing AE, investigational site 
personnel will continue to follow-up with the patient until AE resolution is reached and 
documented. If, after 30 days from the study completion date, the AE is still continuing but 
not assessed as serious, the outcome will be recorded as “not recovered,” and no further 
follow-up will be necessary.  
All AEs identified will be recorded in the eCRF from the time of study drug administration 
until completion of the last study-related procedure (Day 168 or ET). All SAEs will be 
reported from the time the patient signs an ICF until completion of the last study-related 
procedure (Day 168 or ET). 
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 and urinary nitrites should be reported as a urinary tract 
infection). Investigators must record their opinions concerning the relationship of the AE to 
the investigational product in the eCRF. 
Patients (or their designees, if appropriate) may be provided with a “study card” indicating 
the name of the investigational product, the study number, the Investigator’s name, a 
24-hour emergency contact number, and, if applicable, excluded concomitant medications. 
11.3.2 Serious Adverse Event Reporting 
In the event of any SAE reported or observed during the study (whether or not attributable 
to the study drug), investigational site personnel will report it immediately (within 24 hours 
of becoming aware of the SAE) by telephone call, fax, or email to Allakos, Inc.  
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. 
The Investigator will notify the Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC) according to its guidelines. All SAE 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. 
If additional visits are required, the patient will be asked to return to the clinic for further 
follow‐up. 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: 
• The event resolves 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 49 of 75 
 
 
• 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 refuses to provide additional information, patient is lost to 
follow-up after demonstration of due diligence with follow-up efforts) 
11.3.3 Pregnancy 
Female patients must inform the study 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 further treatment with study drug. An uncomplicated pregnancy will not 
be considered an AE or SAE, but all pregnancies will be followed through term. 
Pregnancies are reported if they occur in female patients or in the sexual partners of male 
patients from the time the patient is first exposed to the investigational product until 
Day 168 or ET. 
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. 
11.4 Anaphylaxis 
Signs or symptoms of anaphylaxis will be carefully monitored and treated according to 
standard of care. Emergency crash cart equipment will be available at all times during the 
conduct of the study.  
11.5 
Medical Monitoring 
The regional Medical Monitor will be the primary point of contact to report medical 
concerns or questions regarding study eligibility or patient safety. 
EU Regional Medical Monitor: 
Name:  
 
Edgar J. Fenzl, MD 
Mobile: 
 
+49-172-673 8556 
Email:  
 
edgar.fenzl@fgk-cro.com 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 50 of 75 
 
 
Sponsor and US Regional Medical Monitor: 
Name:  
 
Alejandro Dorenbaum, MD 
Mobile: 
 
1-415-328-9115 
Email:  
 
adorenbaum@allakos.com 
12 DISCONTINUATION AND REPLACEMENT OF PATIENTS 
12.1 
Early Discontinuation of Study Drug  
A patient may be discontinued from study treatment at any time if the patient, the 
Investigator, or the Sponsor feels that it is not in the patient’s best interest to continue. The 
following is a list of possible reasons for study treatment discontinuation:  
• Patient’s withdrawal of consent 
• Patient is not compliant with study procedures 
• AE that, in the opinion of the Investigator, results in it being in the best interest of 
the patient to discontinue study treatment 
• Protocol violation requiring discontinuation of study treatment 
• Loss to follow-up 
• Sponsor’s request for ET of study 
• Positive pregnancy test (females) 
If a patient is withdrawn from treatment due to an AE, the patient will be followed and 
treated by the Investigator until the abnormal parameter or symptom has resolved or 
stabilized.  
All patients who discontinue study treatment should come in for an ET visit as soon as 
possible. 
All patients 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 a reason for patient 
withdrawals. The reason for the patient’s withdrawal from the study will be specified in the 
patient’s source documents. Refer to Table 1 for ET procedures. 
12.2 Withdrawal of Patients from the Study 
Participation of a patient will be discontinued in the event that:  
• An AE or SAE that, in the judgment of the Investigator, requires treatment 
withdrawal due to its nature, severity, or required treatment, regardless of the causal 
relationship to treatment 
• Protocol violations, including non-compliance, loss to follow-up 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 51 of 75 
 
 
• Occurrence of an exclusion criterion that is clinically relevant and affects the 
patient’s safety, if discontinuation is considered necessary by the Investigator 
and/or Sponsor  
• Serum transaminases (ALT and/or AST) >3 × upper limit of normal (ULN) AND 
total bilirubin >2 × ULN (confirmed by subsequent repeat) without an alternative 
explanation 
• Elevation of ALT or AST >3 × ULN (confirmed by repeat) 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 drug, as defined in Section 7.1  
• Withdrawal of the patient’s consent 
• Participation in any other trial during the duration of this trial 
• Loss of ability to freely provide consent through imprisonment or involuntary 
incarceration for treatment of either a psychiatric or physical (e.g., infectious 
disease) illness 
• Discretion of the Investigator 
All patients 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 a reason for patient 
withdrawals. The reason for the patient’s withdrawal from the study will be specified in the 
patient’s source documents. As noted above, patients who discontinue study treatment early 
(i.e., they withdraw prior to Day 168) should have an ET visit. Refer to Table 1 for ET 
procedures. Patients who withdraw after Day 84 but prior to Day 168 should be encouraged 
to come in for a final visit.  
12.3 
Replacement of Patients 
Patients who do not meet all eligibility criteria at Screening or who qualify at Screening but 
do not enter the Run-in period within 6 weeks may be rescreened once and assigned a new 
Screening number.  
Patients who withdraw prematurely from the study will not be replaced.  
13 PROTOCOL VIOLATIONS 
A protocol violation occurs when the patient, Investigator, or Allakos, Inc., fails to adhere 
to protocol requirements affecting the inclusion or exclusion criteria, patient safety, or 
primary endpoint. Protocol violations for this study include, but are not limited to, the 
following: 
• Failure to meet inclusion/exclusion criteria 
• Use of a prohibited concomitant medication 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 52 of 75 
 
 
• Failure to comply with GCP guidelines will also result in a protocol violation  
Allakos, Inc., will determine if a protocol violation will result in withdrawal of a patient. 
When a protocol violation occurs, it will be discussed with the Investigator and a Protocol 
Violation Form detailing the violation will be generated. This form will be signed by a 
Sponsor representative and the Investigator. A copy of the form will be filed in the 
investigational site’s regulatory binder and in the Sponsor’s files. 
14 DATA SAFETY MONITORING 
14.1 
General Safety Monitoring 
The Sponsor’s Medical Monitor will review data relating to safety and to the conduct of the 
study as it becomes available. 
14.2 Data Monitoring Committee 
A DMC will be convened periodically to monitor the safety of patients over the course of 
the study. Members of the DMC can request the identities of patients’ study drugs if 
needed. Other information about the DMC can be found in the DMC charter.  
14.3 
Study Stopping Rules 
The trial must be discontinued prematurely in the event of any of the following:  
• A life-threatening adverse event that is possibly or probably related to treatment 
• A fatal adverse event that is possibly or probably related to treatment 
• New information leading to unfavorable risk-benefit judgment of the study drug, 
e.g., occurrence of significant previously unknown adverse reactions, unexpectedly 
high intensity or incidence of known adverse reactions, or other unfavorable safety 
findings 
• >25% of patients 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 patients making completion of the trial within an acceptable 
time frame unlikely 
• Discontinuation of development of the Sponsor’s study drug 
Regulatory Authorities and IRBs/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 Regulatory Authorities. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 53 of 75 
 
 
15 STATISTICAL METHODS AND CONSIDERATIONS 
This section outlines the nature and rationale for the statistical methods to be used for the 
analysis of the data from the study. Baseline will be defined as the last measurement before 
the patient is randomized. All data will be included in data listings. A separate Statistical 
Analysis Plan (SAP), which must be documented as completed prior to unblinding the 
study, will describe data handling and statistical techniques in full detail, except missing 
PK data handling and PK analysis methods will be described in the PK report. The SAP 
will contain any modifications to the analysis plan described below in this section.  
15.1 
Analysis Populations 
15.1.1 Safety Population 
All safety analyses will be performed in the Safety Population, defined as all patients who 
were randomized and received at least 1 dose of the study drug. Patients will be analyzed 
according to the study drug they received. 
15.1.2 Pharmacokinetics Population 
The PK analysis of AK001 will be performed in the PK Population, defined as patients 
with serum concentration data obtained at pre-defined time points.  
15.1.3 Efficacy Populations 
The main population for efficacy will be the Modified Intention-to-Treat Population, 
defined as all patients randomized who receive at least 1 dose of study drug and have a 
valid Baseline measurement and at least 1 post-baseline efficacy assessment. Patients will 
be analyzed for efficacy according to the group to which they were randomized.   
In addition, the primary efficacy analyses will also be performed for the Per-Protocol 
Population, defined as patients who have a Week 12 visit and valid efficacy measurements. 
15.2 
Demographic and Baseline Characteristics 
Demographic and Baseline variables that will be summarized by treatment and dose group 
include: 
• Demographics 
• Medical history 
• Complete PE 
• Safety variables including vital signs and laboratory tests (including chemistries, 
hematology, and urinalysis) obtained at Screening, and ADA obtained on Day 0 
pre-dose 
15.3 
Analysis of Primary Endpoint 
The effect of 2 different dose levels of AK001 in combination with an INS versus the INS 
alone on the reduction in size of nasal polyps as evaluated by the change from Baseline to 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 54 of 75 
 
 
Week 12 after the start of treatment in TPS (Appendix 2 Section 19.2) will be displayed for 
each treatment group by study visit using summary statistics, including the number of 
observations, the mean, median, standard deviation (SD), and range. Each active treatment 
group will be compared separately with the placebo group for change from Baseline in TPS 
by using a mixed effect repeated measures analysis of variance (ANOVA) model with 
specific contrast statement for Week 12 and for each comparison separately. Adjustment in 
alpha for multiple comparisons will be controlled according to the Hochberg method, in 
which, if the efficacy comparison of the high active arm versus placebo is statistically 
significant at the 0.05 level, no penalty will be assessed to the comparison of the low active 
arm versus the placebo arm. Otherwise, the low active arm versus the placebo arm will be 
compared at the 0.025 level. 
Missing values for the primary endpoint will be imputed by 2 methods: last observation 
carried forward and worst observation carried forward. Imputations will be done on the 
total score level and not on the individual item level. Due to the sample size, no multiple 
imputation technique is intended.  
15.4 
Analysis of Secondary Endpoints  
Additional efficacy measures will be analyzed in support of the primary efficacy endpoint 
results.  
In addition to change from Baseline in TPS (Appendix 2 Section 19.2), absolute values and 
percentage changes from Baseline will be analyzed separately using the same repeated 
measures model described above. A responder analysis will also be considered. The 
response definition and its appropriate analysis methodology will be presented in the SAP. 
The numbers (percentages) of patients who are responders and time to first response for 
each active treatment group will be compared separately with the placebo group, if feasible. 
Examination of the treatment effect over time for TPS (Appendix 2 Section 19.2), UPSIT 
(Appendix 4 Section 19.4), and patient-reported symptoms of sinusitis (SNOT-22) 
(Appendix 5 Section 19.5) will be examined using an appropriate similar repeated 
measures ANOVA. The stratification factor, presence or absence of asthma, may be 
included in the model. The details of the analytical methods will be presented in the SAP.  
Size of polyps as evaluated by Lund-Mackay score (Appendix 3 Section 19.3) at selected 
Investigator sites by CT scan (CT scans are optional and will only be done at Investigator 
sites at which appropriate and timely regulatory approval or authorization can be granted); 
PNIF; UPSIT (Appendix 4 Section 19.4); and patient-reported SNOT-22 (Appendix 5 
Section 19.5), VAS (Appendix 6 Section 19.6), clinical symptoms improvement scale3 
(Appendix 6 Section 19.6), and SF-36 (Appendix 7 Section 19.7) scores for each active 
treatment group will be compared separately with the placebo group using a repeated 
measure ANOVA with contrast statements for comparison at Week 12 as well as other time 
points in the study. 
15.5 
Analysis of Exploratory Endpoints 
The exploratory analyses are not powered for statistical significance.  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 55 of 75 
 
 
Potentially, markers of MCs and eosinophils and inflammatory response in blood for each 
active treatment group will be compared separately with the placebo group, with suitable 
analyses that will be described in the SAP. 
Enrollment in this study is designed for presence or absence of asthma as a stratification 
factor; thus, asthma will be equally distributed among the 3 groups. This stratification 
factor may be used in the analyses of the primary and secondary analyses described above. 
Additional exploratory analyses are planned to explore any possible trend in favor of 
AK001 in the subgroup of asthmatic patients.  
In patients with comorbid asthma, use of asthma rescue therapy will be summarized by 
number and percentage. Changes from Baseline; percentage changes from Baseline; 
absolute TPS (Appendix 2 Section 19.2); pulmonary function (assessed using spirometry) 
as evaluated by FEV1, FVC, FEF; and ACT (Appendix 8 Section 19.8) for each active 
treatment group will be compared separately with the placebo group using the same 
repeated measures model described above, to detect any potential trend at Week 12 and at 
other visits. 
15.6 
Safety Analysis 
Safety and tolerability will be assessed throughout the study by monitoring and evaluating 
TEAEs, including any complications resulting from the IV infusion, and changes in vital 
signs and in clinical safety laboratory test (including ADA) and PE findings. All safety and 
tolerability endpoints will be summarized by treatment. Baseline for all safety endpoints 
will be defined as the last recorded observation before the administration of the IV infusion 
of study drug. Safety measures, including AEs, clinical safety laboratory tests (including 
ADA), vital signs, PEs, and concomitant medication usage, will be summarized 
descriptively. For quantitative variables, descriptive statistics, including number of 
observations, means, medians, SDs, and ranges, will be provided for the values themselves 
as well as for the changes from Baseline by treatment group at each study visit. Qualitative 
variables will be summarized using counts and percentages in each treatment group at each 
study visit.  
Adverse Events: 
All AEs will be coded using the latest version of the Medical Dictionary for Regulatory 
Activities (MedDRA) and will be classified by MedDRA system organ class (SOC) and 
preferred term. The summaries of AEs will be based on TEAEs. A TEAE is defined as an 
AE reported in the clinical database with a date of onset (or worsening) on or after the start 
date of study drug through the end of the study.  
The following information will be presented for AEs: 
• TEAEs by SOC and preferred term 
• TEAEs by maximum severity, SOC, and preferred term 
• Drug-related TEAEs by SOC and preferred term 
• TEAEs leading to withdrawal by SOC and preferred term 
• Serious TEAEs by SOC and preferred term 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 56 of 75 
 
 
All AEs will be collected starting from the first study drug administration through Day 168 
or ET. Severity will be assessed by the Investigator using the protocol-defined grading 
scales (Section 11.1). All AEs will also be judged by the Investigator as to whether they are 
clinically significant and related to study drug.  
Vital Signs: 
Body temperature, supine systolic and diastolic blood pressure, pulse, and respiratory rate 
will be measured at Screening and on Days -3, 0, 14, 21, 49, 84, 112, and 168 or ET. On 
Days 0, 21, and 49, vital signs will be measured pre-dose, every 15 minutes after the start 
of infusion, and immediately following the end of infusion. All vital signs will be measured 
after the patient has been in the supine position for ≥5 minutes.  
Descriptive statistics will be used to summarize vital signs at Baseline, each visit and time 
point, and the change from Baseline for each visit and time point.  
Laboratory Assessments: 
Samples will be obtained for the clinical safety laboratory tests (hematology, chemistry, 
urinalysis) and for ADA specified in Table 1 and Sections 9.3.2, 9.3.3, 9.3.5, and 9.4.  
Descriptive statistics will be used to summarize laboratory results at Baseline, each visit, 
and the change from Baseline for each visit. In addition, shift tables will summarize the 
laboratory results relative to normal reference ranges at Baseline and each post-baseline 
time point. 
Physical Examinations: 
A complete PE will be performed at Screening, and symptom-directed PEs will be 
performed pre-dose (and post-dose as indicated) on Days 0, 21, and 49 and on Days 14, 21, 
84, 112, and 168 or ET. Shift tables will summarize the examination results as normal or 
abnormal at Baseline and at the end of study. 
Prior and Concomitant Medications: 
All medications (prior and current) will be coded using the latest version of the World 
Health Organization Anatomical Therapeutic Chemical (ATC) Classification System. 
Concomitant medications will be summarized by ATC Class 1, ATC Class 3, and preferred 
term. 
15.7 
Sample Size and Randomization 
The study will be conducted at approximately 14 investigational sites in the European 
Union and the United States, and approximately 70 patients will be enrolled. 
This study will evaluate the effect of 2 different dose levels of AK001 in combination with 
an INS versus the INS plus placebo on the reduction in size of nasal polyps. Assuming 
equal efficacy effect of the 2 active treatment arms, a planned sample size of approximately 
70 patients (25 mg of AK001 [n=25], 250 mg of AK001 [n=25], and a corresponding 
placebo (n=20]) will ensure at least 80% power to detect a difference in mean nasal polyp 
scores between the placebo group (Mean= -0.3; SD ≤1.128) and each of the AK001 groups 
(Mean= -1.9; SD ≤2.064) with an alpha of 0.05. PASS 11, Version 11.0.10, was used for 
this power analysis. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 57 of 75 
 
 
15.8 
Interim Monitoring 
No interim analyses are planned for evaluating efficacy. However interim safety 
monitoring will be performed according to the DMC charter. 
16 DATA COLLECTION, RETENTION, AND MONITORING 
16.1 
Data Collection Instruments 
All staff at each investigational site will adhere to Good Documentation Practices. Data 
will be entered into eCRFs using source document data. Source documents may include, 
but are not limited to, laboratory data, recorded data from automated instruments, medical 
progress notes, and email correspondence.  
16.2 
Data Management Procedures 
The data will be entered into a validated database. The Data Management group will be 
responsible for data processing in accordance with procedural documentation. Database 
lock will occur once quality assurance procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good 
computing practices that meet FDA and local applicable authority guidelines for the 
handling and analysis of data for clinical trials. 
16.3 
Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data 
validation checks will be implemented and applied to the database on a regular basis. 
Queries are entered, tracked, and resolved through the electronic data capture system 
directly. The study database will be updated in accordance with the resolved queries. All 
changes to the study database will be documented. 
16.4 
Archiving of Data 
The database is safeguarded against unauthorized access by established security 
procedures; appropriate backup copies of the database and related software files will be 
maintained. Databases are backed up by the database administrator in conjunction with any 
updates or changes to the database.  
At critical junctures of the protocol (e.g., production of interim reports and final reports), 
data for analysis is locked and cleaned per established procedures. 
16.5 
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, the 
investigational sites will retain a copy of all study records in a limited-access storage room 
for a minimum of 2 years after notification that the investigations have been discontinued 
and the FDA has been notified or for 2 years after all marketing applications have been 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 58 of 75 
 
 
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 sub-categories: 
• Financial agreements 
• Regulatory documents 
• IRB/IEC documents 
• Drug accountability 
• Correspondence 
• Medical reports 
• Patient data 
• Monitoring visit reports 
• Sample eCRFs and eCRF guidelines 
16.6 
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. 
16.7 
Patient Confidentiality 
Only the patient’s number and demographics will be recorded in the eCRF. If the patient’s 
name appears on any other source document collected (e.g., hospital discharge summary), 
it must be removed from the document before the document is transcribed to the eCRF. All 
study findings will be stored in electronic databases. The patients will give explicit written 
permission for representatives of the Sponsor, Regulatory Authorities, and the IRB/IEC to 
inspect their medical records to verify the information collected about them. Patients will 
be informed that all personal information made available for inspection will kept 
confidential to the extent permitted by all applicable state, local, and federal data 
protection/privacy laws and/or regulations and will not be made publically available. If the 
results of the trial are published, the patient’s identity will remain confidential.  
Patients will be advised not to share their study information with other patients.  
17 ADMINISTRATIVE, ETHICAL, AND REGULATORY CONSIDERATIONS 
The study will be conducted in a manner consistent with all applicable Regulatory 
Authority and IRB/IEC regulations (e.g., ICH Guideline for Good Clinical Practice [GCP, 
CPMP/ICH/135/95], the Declaration of Helsinki [in its currently acknowledged version], 
Institutional Review Boards [21 CFR 56], and Obligations of Clinical Investigators 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 59 of 75 
 
 
[21 CFR 312]) as well as in keeping with applicable local law(s) and regulation(s). This 
may include audits by the Sponsor and the Sponsor representatives, respectively, and/or 
inspections by Regulatory Authority representatives at any time. The Investigator must also 
comply with all applicable privacy regulations (e.g., Health Insurance Portability and 
Accountability Act of 1996 [HIPAA], European Union Data Protection Directive 
95/46/EC). In addition, the Investigator must agree to the inspection/audit of study-related 
records by the Regulatory Authority/Sponsor and Sponsor representatives and must allow 
direct access to source documents to the Regulatory Authority/Sponsor and Sponsor 
representatives. 
17.1 
Protocol Amendments 
Protocol amendments cannot be implemented without prior written IRB/IEC approval 
except as necessary to eliminate immediate safety hazards to patients. Written approval of a 
protocol amendment is not required prior to implementation of changes to the protocol that 
eliminate immediate hazard to the patient; however, approval must be obtained as soon as 
possible thereafter. Any agreed amendments must also be signed by the Investigator. 
17.2 
Institutional Review Boards and Independent Ethics Committees 
The protocol and ICF will be reviewed and approved by the IRB/IEC of each participating 
center prior to study initiation. Serious adverse events, regardless of causality, will be 
reported to the IRB/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 the 
protocol; protocol amendments; the IB; ICFs; information concerning patient recruitment, 
payment, and compensation procedures; and other pertinent information) will be submitted 
to the IRB/IEC. The IRB’s/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’s/IEC’s unconditional approval statement will be transmitted by the Investigator to 
Allakos, Inc., prior to the shipment of study supplies to the investigational 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. 
Protocol and/or informed consent changes may not be initiated without prior written 
IRB/IEC approval except when necessary to eliminate immediate hazards to the patients or 
when the change(s) involves only logistical or administrative aspects of the study. Such 
changes 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 patients of the conduct of the study, 
annual updates and/or requests for re-approval, and completion of the study. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 60 of 75 
 
 
17.3 
Informed Consent Form  
Prior to undergoing any study-related procedures, all patients must consent to participate in 
the study.  
In accordance with ICH GCP Guidelines 4.3.3, the Investigator must inform the patient’s 
primary physician about the patient’s participation in the trial if the patient has a primary 
physician and if the patient agrees to the primary physician being informed. 
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 ICF and review must be 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 undergo any study-related procedures. The patient will 
receive a copy of the signed and dated ICF, and the original will be retained in the 
investigational 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. 
17.4 
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 between 
Allakos and each investigational site. The publication or presentation of any study results 
shall comply with all applicable privacy laws, for example, the HIPAA.  
17.5 
Clinical Trial Registration 
This clinical trial will be registered in the US on the “clinicaltrials.gov” clinical trial 
registry website, as required by 121 STAT. 823, and on EudraCT in Europe, as necessary. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 61 of 75 
 
 
18 
REFERENCES 
1. 
Hedman J, Kaprio J, Poussa T, Nieminen MM. Prevalence of asthma, aspirin 
intolerance, nasal polyposis and chronic obstructive pulmonary disease in a 
population-based study. Int J Epidemiol 1999;28(4):717-22. 
2. 
Mygind N, Dahl R, Bachert C. Nasal polyposis, eosinophil dominated 
inflammation, and allergy. Thorax 2000;55 Suppl 2:S79-83. 
3. 
Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European 
Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl 2012(23):3 p 
preceding table of contents, 1-298. 
4. 
Pearlman AN, Chandra RK, Conley DB, Kern RC. Epidemiology of nasal polyps. 
In: Nasal Polyposis, eds. T.M. Onerci and B.J. Ferguson. Springer-Verlag: Berlin 
Heidelberg 2010. In. 
5. 
Bachert C, Gevaert P, Holtappels G, Johansson SG, van Cauwenberge P. Total and 
specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy 
Clin Immunol 2001;107(4):607-14. 
6. 
Kiwamoto T, Kawasaki N, Paulson JC, Bochner BS. Siglec-8 as a drugable target to 
treat eosinophil and mast cell-associated conditions. Pharmacol Ther 
2012;135(3):327-36. 
7. 
US Department of Health and Human Services. Common Terminology Criteria for 
Adverse Events Version 4.0. 28May2009. Available from: 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf. Accessed 01Feb2016. 
 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 62 of 75 
 
 
19 APPENDICES 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 63 of 75 
 
 
19.1 Appendix 1: Contraception Guidelines 
Contraception guidelines vary by location; local guidelines will be followed.  
Female patients must be post-menopausal for at least 1 year with documented 
follicle-stimulating hormone (FSH) >30 IU/L, surgically sterile (tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 3 months, or, if of child-bearing 
potential, willing to use a highly effective method of contraception from Screening until at 
least 17 weeks after the last dose of the study drug is administered, which corresponds to 
approximately 5 half-lives of AK001. 
Male patients with female partners of childbearing potential must agree to use a highly 
effective method of contraception from Screening until at least 17 weeks after the last dose 
of the study drug was administered, which corresponds to approximately 5 half-lives of 
AK001. 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. 
Highly effective methods of contraception include the following practices:  
a) Complete abstinence (acceptable only if it is established before the patient 
participates in the trial that this is the preferred and usual lifestyle of the patient) 
b) Prescription hormonal contraceptives (oral, injected, or implanted) for 2 or more 
menstrual cycles prior to Screening 
c) Intrauterine device 
d) Surgical sterilization for male patients with female partners 
i. 
Tubal ligation/hysterectomy/bilateral oophorectomy or  
ii. 
Vasectomy 
The double barrier method of contraception (e.g., condom with cap, diaphragm, or sponge 
with spermicide) alone is not considered a highly effective method but may be used in 
conjunction with 1 of the above methods. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 64 of 75 
 
 
19.2 Appendix 2: Polyp Scoring System  
Polyp Scoring System Used to Evaluate Polyp Size in Each Nostril by Nasal Endoscopy 
Polyp Score 
Polyp Size 
0 
No polyps 
1 
Small polyps in the middle meatus not reaching below the inferior border of the middle 
turbinate 
2 
Polyps reaching below the lower border of the middle turbinate 
3 
Large polyps reaching the lower border of the inferior turbinate or polyps medial to the 
middle turbinate 
4 
Large polyps causing complete obstruction of the inferior nasal cavity 
Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Omalizumab is effective in allergic and 
nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol 2013;131(1):110-6 e1. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 65 of 75 
 
 
19.3 Appendix 3: Lund-Mackay Scoring System 
The Lund-Mackay scoring system as presented in the table below will be used to measure 
the polyp size in each nostril by computed tomography (CT) at selected Investigative sites. 
The CT scans are optional and will only be done at Investigator sites at which appropriate 
and timely regulatory approval or authorization can be granted. 
Lund-Mackay Scoring System 
 
Possible Scores1 
Maxillary  
0-2 
Anterior ethmoid  
0-2 
Posterior ethmoid  
0-2 
Sphenoid  
0-2 
Frontal  
0-2 
Osteomeatal complex  
0 or 2 
Total 
 
1. Scale: 0 = absence; 1 = partial opacification; 2 = complete opacification. 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 66 of 75 
 
 
19.4 Appendix 4: University of Pennsylvania Smell Identification Test™ 
The University of Pennsylvania Smell Identification Test consists of 4 booklets, each 
containing 10 odorants with 1 odorant per page. The stimuli are embedded in plastic 
microcapsules on brown strips at the bottom of each page. Above each odorant strip is a 
multiple-choice question with 4 alternative words to describe the odor as in the model of a 
test page below. The patient is asked to release the odorant by rubbing the brown-strip with 
the tip of a pencil and to indicate which of 4 words best describes the odor. Thus, each 
subject receives a score out of 40 possible correct answers (Scadding G, Hellings P, Alobid 
I, Bachert C, Fokkens W, van Wijk RG, et al. Diagnostic tools in Rhinology EAACI 
position paper. Clin Transl Allergy 2011;1[1]:2). 
 
 
Fornazieri MA, Pinna Fde R, Bezerra TF, Antunes MB, Voegels RL. Applicability of the University of Pennsylvania 
Smell Identification Test (SIT) in Brazilians: pilot study. Braz J Otorhinolaryngol 2010;76(6):695-9. 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 67 of 75 
 
 
19.5 Appendix 5: Sino-nasal Outcome Test-22 
 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 68 of 75 
 
 
19.6 Appendix 6: Visual Analogue Scales for Symptoms of Rhinosinusitis and 
Clinical Symptoms Improvement Scale 
 
The VASs rank symptoms from 0 (not troublesome) to 10 (most troublesome) on 
10 cm-long scales as below. 
 
How troublesome are each of your following symptoms of rhinosinusitus? 
 
a) 
Anterior nasal discharge 
 
Not troublesome 
 
 
 
 
 
Most troublesome 
 
b) 
Posterior nasal discharge 
 
Not troublesome 
 
 
 
 
 
Most troublesome 
 
c) 
Nasal congestion, blockade, or obstruction 
 
Not troublesome 
 
 
 
 
 
Most troublesome 
 
d) 
Decreased sense of smell 
 
Not troublesome 
 
 
 
 
 
Most troublesome 
 
e) 
Facial pain or pressure 
 
Not troublesome 
 
 
 
 
 
Most troublesome 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 69 of 75 
 
 
The clinical symptoms improvement scale* ranks symptom troublesomeness from 0 (not 
troublesome) to 10 (worst thinkable troublesome) on a 10 cm-long scale as below. 
 
How troublesome are your symptoms of rhinosinusitis? 
 
Not troublesome 
 
 
 
 
 
Worst thinkable troublesome 
 
The symptomatology or symptom troublesomeness can be divided into “mild,” “moderate,” 
and “severe” categories based on total score: 
• 
Mild=0 through 3 
• 
Moderate= >3 through 7 
• 
Severe= >7 through 10 
 
 
*Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European Position Paper on 
Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl 2012(23):3 p preceding table of contents, 1-298. 
 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 70 of 75 
 
19.7 Appendix 7: 36-Item Short Form Health Survey 
 
SF-36v2 Health Survey Single-Item Presentation Text Standard, United States (English) 
Note: Item SF36v2_BP1 (Item #21) has 6 answers, not 5 answers; see entry for item at end of sheet for more detail. 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
 
Your Health and Well-Being 
 
 
 
 
 
 
 
 
This survey asks for your views about your 
health.  This information will help keep track of 
how you feel and how well you are able to do 
your usual activities. Thank you for completing 
this survey! 
 
For each of the following questions, please 
select the one box that best describes your 
answer. 
 
 
 
 
 
SF36v2_GH1 
None 
In general, would you say your health is: 
Excellent 
Very good 
Good 
Fair 
Poor 
SF36v2_HT 
None 
Compared to one year ago, how would you 
rate your health in general now? 
Much 
better 
now than 
one year 
ago 
Somewhat 
better now 
than one 
year ago 
About the 
same as 
one year 
ago 
Somewhat 
worse 
now than 
one year 
ago 
Much 
worse 
now than 
one year 
ago 
SF36v2_PF01 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in vigorous 
activities, such as running, lifting heavy 
objects, participating in strenuous sports?  If 
so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF02 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in moderate 
activities, such as moving a table, pushing a 
vacuum cleaner, bowling, or playing golf?  If 
so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF03 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in lifting or 
carrying groceries?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF04 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in climbing 
several flights of stairs?  If so, how much? 
Yes, 
limited a 
Yes, 
limited a 
No, not 
limited at 
  
  


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 71 of 75 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
lot 
little 
all 
SF36v2_PF05 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in climbing one 
flight of stairs?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF06 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in bending, 
kneeling, or stooping?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF07 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in walking more 
than a mile?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF08 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in walking 
several hundred yards?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF09 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in walking one 
hundred yards?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF10 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in bathing or 
dressing yourself?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_RP1 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities?  
Cut down on the amount of time you spent on 
work or other activities as a result of your 
physical health 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RP2 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Accomplished less than you would like as a 
result of your physical health 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RP3 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities?  
Were limited in the kind of work or other 
activities as a result of your physical health 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RP4 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Had difficulty performing the work or other 
activities as a result of your physical health (for 
example, it took extra effort) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 72 of 75 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
SF36v2_RE1 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Cut down on the amount of time you spent on 
work or other activities as a result of any 
emotional problems (such as feeling 
depressed or anxious) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RE2 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities?  
Accomplished less than you would like as a 
result of any emotional problems (such as 
feeling depressed or anxious) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RE3 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Did work or other activities less carefully than 
usual as a result of any emotional problems 
(such as feeling depressed or anxious) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_SF1 
None 
During the past 4 weeks, to what extent has 
your physical health or emotional problems 
interfered with your normal social activities with 
family, friends, neighbors, or groups? 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
SF36v2_BP1 
None 
How much bodily pain have you had during the 
past 4 weeks? 
See end of document for answers #1-#6 
SF36v2_BP2 
None 
During the past 4 weeks, how much did pain 
interfere with your normal work (including both 
work outside the home and housework)? 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
SF36v2_VT1 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you feel full of life? 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH1 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you been very nervous?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH2 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you felt so down in the dumps that 
nothing could cheer you up?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 73 of 75 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
SF36v2_MH3 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you felt calm and peaceful?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_VT2 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you have a lot of energy?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH4 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you felt downhearted and depressed?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_VT3 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you feel worn out?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH5 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you been happy?  
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_VT4 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you feel tired?  
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_SF2 
None 
During the past 4 weeks, how much of the time 
has your physical health or emotional 
problems interfered with your social activities 
(like visiting with friends, relatives, etc.)? 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
 SF36v2_GH2 
How TRUE or FALSE is the following 
statement for you? 
I seem to get sick a little easier than other 
people. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 
SF36v2_GH3 
How TRUE or FALSE is the following 
statement for you? 
I am as healthy as anybody I know. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 74 of 75 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
SF36v2_GH4 
How TRUE or FALSE is the following 
statement for you? 
I expect my health to get worse. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 
SF36v2_GH5 
How TRUE or FALSE is the following 
statement for you? 
My health is excellent. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 
SF-36v2® Health Survey  1992, 1996, 2000, 2010 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)). 
 
Data for item SF36v2_BP1 (item #21 in the survey template) 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
Answer 
Text 6 
SF36v2_BP1 
None 
How much bodily pain have you had during the 
past 4 weeks? 
None 
Very mild 
Mild 
Moderate 
Severe 
Very severe 
SF-36v2® Health Survey Ó 1992, 1996, 2000, 2010 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Single-Item Presentation Text Standard, United States (English)). 
 


Protocol AK001-002 Amendment 2.3 
          Confidential 
 
Final 
Date: 27OCT2016 
Page 75 of 75 
 
19.8 Appendix 8: Asthma Control Test™ 
 
Asthma Control Test™ Single-Item Presentation Text, United States (English) 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
 
Asthma Control Test™ 
 
 
 
 
 
 
 
This survey was designed to help you 
describe your asthma and how your asthma 
affects how you feel and what you are able 
to do.  For each of the following questions, 
please select the one box that best 
describes your answer. 
 
 
 
 
 
 
ACT1 
None 
In the past 4 weeks, how much of the time did your 
asthma keep you from getting as much done at 
work, school or at home? 
All of the 
time 
Most of the 
time 
Some of 
the time 
A little of 
the time 
None of 
the time 
ACT2 
None 
During the past 4 weeks, how often have you had 
shortness of breath? 
More than  
once a 
day 
Once a 
day 
3 to 6 
times a 
week 
Once or 
twice 
a week 
Not at all 
ACT3 
None 
During the past 4 weeks, how often did your 
asthma symptoms (wheezing, coughing, shortness 
of breath, chest tightness or pain) wake you up at 
night or earlier than usual in the morning? 
4 or more 
nights a 
week 
2 to 3 
nights a 
week 
Once a 
week 
Once or 
Twice 
Not at all 
ACT4 
None 
During the past 4 weeks, how often have you used 
your rescue inhaler or nebulizer medication (such 
as Albuterol, Ventolin®, Proventil®, or Maxair®)? 
3 or more 
times per 
day 
1 or 2 
times per 
day 
2 or 3 
times per 
week 
Once a 
week 
or less 
Not at all 
ACT5 
None 
How would you rate your asthma control during the 
past 4 weeks? 
Not 
Controlled 
at all 
Poorly 
Controlled 
Somewhat  
Controlled 
Well 
Controlled 
Completely 
Controlled 
Asthma Control Test™ © QualityMetric Incorporated 2002, 2004, 2011.  All rights reserved. 
Asthma Control Test™ is a trademark of QualityMetric Incorporated.. 
Single-Item Presentation Text, United States (English). 

SAP_001.pdf: 
 
 
 
Page 1 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Statistical Analysis Plan 
 
Allakos, Inc 
Protocol AK001-002 
 
 
 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 
Study to Evaluate Multiple Doses of AK001 in Patients With 
Moderate to Severe Nasal Polyposis 
 
VERSION 1.0 DATED 16 August 2017 
 
 
 
Sponsor: 
 
Allakos, Inc. 
75 Shoreway Road, Suite A 
San Carlos, CA 94070 
 
 
Prepared by:   
Mojtaba Noursalehi, Ph.D. 
 
 
 
InClin, Inc. 
 
 
 
2000 Alameda De Las Pulgas 
 
 
 
San Mateo, CA 94403 
 
 
 
Version: 
 
1, 16 August 2017 
 
 
 
 
 
 
 




 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 3 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
TABLE OF CONTENTS 
 
1. 
INTRODUCTION ................................................................................................................ 10 
1.1 
GENERAL ..................................................................................................................... 10 
1.2 
PROTOCOL VERSIONS .................................................................................................. 10 
2. 
STUDY  OBJECTIVES ....................................................................................................... 10 
3. 
STUDY DESIGN .................................................................................................................. 12 
4. 
DETERMINATION OF SAMPLE SIZE .......................................................................... 13 
5. 
GENERAL ANALYSIS CONSIDERATIONS ................................................................. 14 
5.1 
CONVENTIONS ............................................................................................................. 15 
5.2 
STANDARD CALCULATIONS ......................................................................................... 15 
5.3 
HANDLING PARTIAL DATES FOR ADVERSE EVENTS AND MEDICATIONS ................... 16 
5.4 
VISIT WINDOWS ........................................................................................................... 17 
5.5 
REVIEW OF BLINDED DATA ......................................................................................... 18 
6. 
ANALYSIS POPULATIONS .............................................................................................. 18 
7. 
STUDY POPULATION ...................................................................................................... 19 
7.1 SUBJECT DISPOSITION ...................................................................................................... 19 
7.2 PROTOCOL DEVIATIONS ................................................................................................... 19 
7.3 DEMOGRAPHIC AND BASELINE CHARACTERISTICS ......................................................... 20 
7.4 MEDICAL HISTORY ........................................................................................................... 20 
7.5 PHYSICAL EXAMINATIONS ............................................................................................... 20 
7.6 VITAL SIGNS ..................................................................................................................... 21 
7.7 ECG .................................................................................................................................. 21 
7.8 FECAL COLLECTION ......................................................................................................... 22 
7.9 ADVERSE EVENTS ............................................................................................................ 22 
7.10 LABORATORY VALUES ................................................................................................... 22 
7.11 ANTI-DRUG ANTIBODY (ADA) ...................................................................................... 22 
7.12 PRIOR AND CONCOMITANT MEDICATIONS ..................................................................... 22 
8. 
EFFICACY ANALYSES ..................................................................................................... 23 
8.1 EFFICACY VARIABLES ...................................................................................................... 23 
8.1.1 PRIMARY EFFICACY VARIABLE ..................................................................................... 23 
8.1.2 SECONDARY EFFICACY VARIABLES .............................................................................. 23 
8.1.3 EXPLORATORY EFFICACY VARIABLES .......................................................................... 24 
8.2 ADJUSTMENTS FOR COVARIATES ..................................................................................... 25 
8.3 HANDLING OF DROPOUTS OR MISSING DATA .................................................................. 25 
8.4 INTERIM ANALYSIS AND DATA MONITORING .................................................................. 25 
8.5 EXAMINATION OF SUBGROUPS ......................................................................................... 25 
8.6 MULTIPLE COMPARISONS/MULTIPLICITY ........................................................................ 25 
8.7 MULTICENTER STUDIES ................................................................................................... 26 
9. 
METHODS OF EFFICACY ANALYSIS .......................................................................... 26 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 4 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
9.1 PRIMARY EFFICACY ANALYSES ....................................................................................... 26 
9.2 SENSITIVITY EFFICACY ANALYSES OF PRIMARY ENDPOINTS .......................................... 27 
9.2.1 ANALYSIS FOR TPS IN PRESENCE OF MISSING DATA ................................................... 27 
9.2.2 THE ANALYSIS WITH TPS INCLUDING TIME AS A REPEATED FACTOR ......................... 28 
9.2.3 ANALYSIS OF TPS IN ABSOLUTE VALUE AND PERCENT CHANGE FROM BASELINE ..... 28 
9.2.4 ALTERNATE ANALYSIS POPULATION ............................................................................ 28 
9.2.5 TIME TO RESPONSE ........................................................................................................ 28 
9.2.6 SUBGROUP ANALYSES ................................................................................................... 29 
9.3 SECONDARY EFFICACY ANALYSES .................................................................................. 29 
9.4 EXPLORATORY EFFICACY ANALYSES .............................................................................. 31 
9.5 PHARMACOKINETIC AND BIOMARKER ANALYSES .......................................................... 31 
10. SAFETY ANALYSES .......................................................................................................... 32 
10.1 ADVERSE EVENTS .......................................................................................................... 33 
10.1.1 SELECTED SUBSETS OF ADVERSE EVENTS .................................................................. 34 
10.1.2 SUBGROUP ANALYSES ................................................................................................. 34 
10.2 CLINICAL LABORATORY EVALUATION .......................................................................... 34 
10.3 VITAL SIGNS ................................................................................................................... 36 
10.4 PRIOR AND CONCOMITANT MEDICATIONS ..................................................................... 37 
11. CHANGES TO PROTOCOL-SPECIFIED ANALYSES ................................................ 37 
12. REFERENCES ..................................................................................................................... 37 
APPENDICES .............................................................................................................................. 39 
APPENDIX A:  VISIT WINDOWS .............................................................................................. 39 
APPENDIX B:  CRITERIA FOR DETERMINING POTENTIALLY CLINICALLY SIGNIFICANT 
VALUES IN LABORATORY TEST RESULTS .............................................................................. 40 
APPENDIX C:  CRITERIA FOR DETERMINING POTENTIALLY CLINICALLY SIGNIFICANT 
VALUES IN VITAL SIGNS ........................................................................................................ 42 
APPENDIX D:  CRITERIA FOR IDENTIFYING ECG VALUES THAT REFLECT POTENTIALLY 
CLINICALLY SIGNIFICANT CHANGE ....................................................................................... 43 
APPENDIX E:  RULES FOR DETERMINING “WORST” VALUE .................................................. 44 
APPENDIX F:  RULES FOR SCORING THE DISEASE ASSESSMENT SCALES .............................. 45 
1. 
TPS .............................................................................................................................. 45 
2. 
THE LUND-MACKAY SCORING SYSTEM ....................................................................... 45 
3. 
UNIVERSITY OF PENNSYLVANIA SMELL IDENTIFICATION TEST™ .............................. 46 
4. 
SINO-NASAL OUTCOME TEST-22 ................................................................................. 47 
5. 
VISUAL ANALOGUE SCALES FOR SYMPTOMS OF RHINOSINUSITIS AND CLINICAL 
SYMPTOMS IMPROVEMENT SCALE ......................................................................................... 48 
6. 
36-ITEM SHORT FORM HEALTH SURVEY ..................................................................... 50 
7. 
ASTHMA CONTROL TEST™ ......................................................................................... 56 
APPENDIX G:  LIST OF REVIEW FILES PROVIDED BY ALLAKOS TO INCLIN ........................... 58 
APPENDIX H:  LIST OF TABLES, FIGURES, AND LISTINGS ...................................................... 59 
LIST OF TABLES ...................................................................................................................... 59 
LIST OF FIGURES .................................................................................................................... 65 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 5 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
LIST OF DATA LISTINGS ......................................................................................................... 66 
APPENDIX I:  TABLE LAYOUTS ............................................................................................... 69 
APPENDIX J:  FIGURE LAYOUTS ........................................................................................... 131 
APPENDIX K:  LISTING LAYOUTS ......................................................................................... 135 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 6 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
LIST OF ABBREVIATIONS 
ACT 
Asthma Control Test™ 
ADA 
Anti-drug Antibody 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
ANOVA 
Analysis of Variance 
ATC 
Anatomical Therapeutic Chemical  
AUC(inf) 
Area under the Plasma Concentration-time Curve from zero hours to 
infinity 
AUC(0-t) 
Area under the Plasma Concentration-time Curve from zero hours to 
time (t)  
CBC 
Complete Blood Count 
CFR 
Code of Federal Regulations 
Cmax 
Maximum Plasma Concentration  
CRS 
Chronic Rhinosinusitis 
CRSsNP 
Chronic Rhinosinusitis without Nasal Polyposis 
CRSwNP 
Chronic Rhinosinusitis with Nasal Polyposis  
CT 
Computed Tomography 
DMC 
Data Monitoring Committee 
eCRF 
Electronic Case Report Form 
ECG 
Electrocardiogram 
ECP 
Eosinophilic Cationic Protein 
ELISA 
Enzyme-linked Immunosorbent Assay 
ET 
Early Termination 
EU 
European Union 
FACS 
Fluorescence-Activated Cell Sorting 
FDA 
Food and Drug Administration 
FEF 
Forced Expiratory Flow  
FEV1 
Forced Expiratory Volume in 1 Second 
FSH 
Follicle-Stimulating Hormone 
FVC 
Forced Vital Capacity 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 7 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
LIST OF ABBREVIATIONS 
GCP 
Good Clinical Practice 
gMean 
Geometric Mean 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human Immunodeficiency Virus 
HR 
Hazard Ratio 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IgE 
Immunoglobulin E 
IgG4 
Immunoglobulin G4 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
IL 
Interleukin 
INS 
Intranasal Steroid 
IRB 
Institutional Review Board 
IXRS 
interactive Voice or Web Response System 
IV 
Intravenous(ly) 
LS 
Least-Squares 
MAb 
Monoclonal Antibody 
MC 
Mast Cells 
MedDRA 
Medical Dictionary for Regulatory Activities 
MPO 
Myeloperoxidase 
PE 
Physical Examination 
PGD2 
Prostaglandin D2  
PH 
Proportional Hazard 
PK 
Pharmacokinetic(s) 
PNIF 
Peak Nasal Inspiratory Flow 
RMPA 
Replacing Missing Value with Placebo Average 
SAE 
Serious Adverse Event 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 8 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
LIST OF ABBREVIATIONS 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SF-36 
36-Item Short Form Health Survey 
Siglec 
Sialic Acid-binding, Immunoglobulin-like Lectin 
SI Units 
International System of Units 
SNOT-22 
Sino-nasal Outcome Test-22 
SOC 
System Organ Class 
t1/2 
Terminal Elimination Half-life 
TEAE 
Treatment-Emergent Adverse Event 
TNF 
Tumor Necrosis Factor 
TPS 
Total Polyp Score  
TSLP 
Thymic Stromal Lymphopoietin 
ULN 
Upper Limit of Normal 
UPSIT 
University of Pennsylvania Smell Identification Test™ 
VAS 
Visual Analogue Scale 
Vz 
Volume of Distribution 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 9 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
DEFINITIONS 
Adverse Event (AE) 
An adverse event is any untoward medical occurrence in 
a patient or a clinical investigation of subject which does 
not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease, whether or 
not considered related to the medicinal product. 
 
 
Intent-to-Treat (ITT) 
Population  
All randomized subjects 
 
 
Modified Intent-to-Treat 
(MITT) Population  
All randomized subjects who take at least one dose of the 
study drug and have both a baseline and at least one post-
baseline efficacy assessment. 
 
 
Per-Protocol (PP) 
Population 
All MITT population subjects who have a week 12 visit 
and valid efficacy measurements. 
 
 
Safety Population 
All randomized subjects who take at least one dose of 
study drug. 
 
Biomarker Population 
All randomized subjects who has at least 1 sample 
obtained for biomarker analysis.  
 
Serious AE (SAE) 
A serious adverse event (SAE) is an adverse event that 
results in any of the following outcomes: death, life-
threatening AE, persistent or significant 
disability/incapacity, inpatient hospitalization or 
prolongation of existing hospitalization, and congenital 
anomaly/birth defect. A medically significant AE is also 
an SAE. 
 
 
Treatment-emergent AE 
(TEAE) 
AEs with an onset time on or after the time of the initial 
dose of study drug or that worsen in intensity or 
treatment attribution. 
 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 10 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
1. INTRODUCTION 
1.1 General 
This document outlines the statistical methods to be implemented during the analyses of 
data collected within the scope of Allakos, Inc. Protocol AK001-002 [A Phase 2, 
Randomized, Double-Blind, Placebo-Controlled, Study To Evaluate Multiple Doses of 
AK001 In Patients With Moderate to Severe Nasal Polyposis].  The purpose of this plan 
is to provide specific guidelines from which the analysis will proceed.  Changes made to 
the SAP after it has been signed but prior to database lock will be documented in an 
amendment. Any deviations from these guidelines will be documented in the clinical 
study report (CSR). 
 
1.2 Protocol Versions 
There are four different versions of the protocol governing this document as listed below. 
Version Country 
Comment 
V 1.0 
US 
Not applicable 
V 2.0 
US and Spain 
Original used for operation 
V 2.1 
UK  
Primarily, extended the study observation to 
Week 24 for safety reasons 
V 2.2 
Netherlands and Belgium 
A Biomarker sub-study with optional 
participation 
V 2.3 
Germany 
Extend the study observation to Week 24; No 
more than 1 patient wil be randomized every 4 
weeks at each site  
 
As a result of these changes, no implications on the analysis of safety or efficacy is 
anticipated. However, a section on exploratory analysis of the Biomarkers will be added 
to the document. The remaining changes in different versions of the amended protocols, 
mostly impact inclusion and exclusion criteria as well as duration of observation.  
2. STUDY  OBJECTIVES  
The primary objective is: 
To evaluate the effect of each of 2 doses of AK001 separately in combination 
with an INS versus the INS alone on the reduction in size of nasal polyps as 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 11 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
evaluated by the change from Baseline to Week 12 after the start of treatment 
in Total Polyp Score (TPS). 
 
The secondary objectives are: 
1. To evaluate the effect of each of 2 doses of AK001 separately in combination 
with an INS versus the INS alone on changes from Baseline to Week 12 after 
the start of treatment in:  
a) 
Size of polyps as evaluated by Lund-Mackay score at selected sites 
by computed tomography (CT) scan  
b) 
Nasal airway patency as evaluated by peak nasal inspiratory flow 
(PNIF) 
c) 
Ability to smell (University of Pennsylvania Smell Identification 
Test™ [UPSIT]) 
d) 
Patient-reported symptoms of sinusitis (Sino-nasal Outcome Test-
22 [SNOT-22] and Visual Analogue Scales [VASs])  
e)         Clinical symptoms improvement scale   
f) 
Quality of life (36-Item Short Form Health Survey [SF-36]) 
2. To evaluate the time to first response in TPS 
3. To evaluate the change in TPS, UPSIT, and patient-reported symptoms of 
sinusitis over time 
4. To evaluate the safety and tolerability of each of 2 doses of AK001 separately 
in combination with an INS during 7 weeks of study drug in patients with 
moderate to severe nasal polyps and whose symptoms are resistant to INSs 
 
The exploratory objectives (in sites with appropriate capability) are: 
In all patients, to:  
1. 
Potentially explore markers of Mast Cells (MC) and eosinophils and 
inflammatory response in blood 
In patients with comorbid asthma, to explore the effect of each of 2 doses of AK001 
separately in combination with an INS versus the INS alone on changes from Baseline to 
Week 12 after the start of treatment in: 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 12 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
2. 
TPS 
3. 
Pulmonary function (forced expiratory volume in 1 second [FEV1], forced 
vital capacity [FVC], and forced expiratory flow [FEF]) 
4. 
Asthma-related symptoms (Asthma Control Test™ [ACT]) 
5. 
Use of asthma rescue therapy  
 
The objective for biomarker analyses is (sub-study; Protocol v2.2): 
In patients at slected investigator sites, to evaluate Baseline and post-treatment levels of 
biomarkers related to the activity of MCs and eosinophils in nasal secretions and blood 
samples . Evaluations will include change from baseline and effect over time. 
  
3. STUDY DESIGN  
This is a Phase 2, randomized, double-blind, placebo-controlled study of the safety and 
tolerability of AK001 compared with placebo in patients with moderate to severe chronic 
nasal polyposis and whose symptoms are resistant to treatment with INSs. At least 50% 
of patients enrolled will have comorbid asthma. 
The study will comprise an up to 4-week Screening period and a 4-week run-in period 
followed by randomization and dosing with AK001 or placebo for 7 weeks followed by a 
9-week observation period. There will be 9 scheduled study visits. The total duration of 
the study will be up to 24 weeks. For UK and Germany, the observation period is 
extended to 17-week, there will be 10 scheduled study visits. As a result, the total 
duration of the study for UK and Germany will be up to approximately 32 weeks.   
After the Screening period, approximately 70 eligible patients will be enrolled and enter a 
run-in period of 4 weeks to achieve a stable regimen with a common intranasal topical 
steroid (NASONEX [mometasone furoate monohydrate] 2 sprays in each nostril twice a 
day) and discontinue any other intranasal topical steroid. Patients will return to the clinic 
at the end of the run-in period prior to dosing with study drug for pre-dose evaluations. 
Patients who continue to meet the eligibility criteria for the study will be randomized, 
will continue to use NASONEX, and will also receive either 25 mg of AK001 (n=25), 
250 mg of AK001 (n=25), or a corresponding placebo (n=20) on Days 0, 21, and 49. The 
randomization will be stratified based on presence or absence of asthma. Patients will be 
required to maintain their Baseline treatments for nasal polyposis unchanged throughout 
participation in this trial.  


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 13 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
A Data Monitoring Committee (DMC) will be convened periodically to monitor the 
safety of patients over the course of the study. Members of the DMC can request the 
identities of patients’ study drugs if needed. Additional information about the DMC can 
be found in the DMC charter.  
A more detailed schedule of events can be found in the protocol Section 4.2. However, 
the general visit schedule of the study is depicted in the following table. 
 
 
Screening 
Period 
Run-in 
Period1 
Treatment Period2 
Post-treatment Period 
Visit 
Screening 
Run-in 
Day 0 
Day 14 
Day 21 
Day 49 
Day 84 
Day 112/ET 
Day 
-56 to -29 
-28 to -1 
0 
14±2 
21±2 
49±2 
84±4 
112±4 or ET 
Week 
[-8 to -4) 
[-4 to 0) 
0 
2 
3 
7 
12 
163 
1 The targeted last measurement is day -3, with a visit window of 2 days. 
2 Measurements could be pre- or post-dose. For complete detail please see protocol section 4.2. 
324 week for UK and Germany. 
 
4. DETERMINATION OF SAMPLE SIZE 
The study will be conducted at approximately 14 investigational sites in the European 
Union and the United States, and approximately 70 patients will be enrolled. 
This study will evaluate the effect of each of 2 doses of AK001 separately in combination 
with an INS versus the INS plus placebo on the reduction in size of nasal polyps. In an 
earlier investigational study, the Sponsor observed similar efficacy effect for both the high 
and low doses administered in this study. Assuming equal efficacy effect of the 2 active 
treatment arms, a planned sample size of approximately 70 patients (25 mg of AK001 
[n=25], 250 mg of AK001 [n=25], and a corresponding placebo (n=20]) will ensure at 
least 80% power to detect a difference in mean nasal polyp scores between the placebo 
group (Mean = -0.3; SD ≤1.128) and each of the AK001 groups (Mean = -1.9; SD ≤2.064) 
with an alpha of 0.05. PASS 11, Version 11.0.10, was used for this power analysis. 
The randomization was enforced with two stratification factors; Region (US vs. non-US), 
as well as Comorbid Asthma (presence vs. absence). A non-study unblinded statistician 
assisted with developing the randomization schedule, incorporating it into the IXRS 
system, and the user acceptance testing (UAT). 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 14 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
The sub-study will be conducted at selected Investigator sites that are participating in the 
main study. It is expected that approximately 20 patients will participate in the sub-study 
regarding the biomarker analysis (protocol v2.2). 
5. GENERAL ANALYSIS CONSIDERATIONS 
The statistical analyses will be reported using summary tables, figures, and data listings. 
Unless otherwise noted, all statistical testing will be two-sided and will be performed at 
the 0.05 significance level. Tests will be declared statistically significant if the calculated 
p-value is < 0.05. Continuous variables will be summarized with means, standard 
deviations, medians, minimums, and maximums. Categorical variables will be 
summarized by counts and by percentage of subjects in corresponding categories.  
 
All summary tables will be presented by treatment group as defined for the population 
included. Baseline summaries will also include a total summary column pooling across 
the two groups. Summary tables presenting results by study visit will include all 
scheduled study visits using informative visit labels (i.e., Baseline, Run-in, Day 0, Week 
2, Week 3, Week 7, Week 12 and Week 16/24 or ET – note: Week 16 will be Week 24 
for UK and Germany).  
 
Individual subject data obtained from the case report forms (CRFs), central or local 
clinical laboratories, electrocardiogram (ECG) readers, imaging core laboratories (CT 
scan), selected IXRS system, and any derived data will be presented by subject in data 
listings. Listings will include relative study day, where negative values will indicate pre-
treatment visits, and data collected after discontinuation of study drug will be flagged as 
follow-up. All data captured on the CRF, including specific descriptions of ‘other’ and 
comment fields, will be included on the listings. Listings will be sorted by subject 
number within each treatment group. 
 
The analyses described in this plan are considered a priori, in that they have been defined 
prior to database lock and prior to breaking the blind. Any analyses performed 
subsequent to breaking the blind will be considered post-hoc and exploratory. Post-hoc 
analyses will be labeled as such on the output and identified in the CSR. 
 
All analyses and tabulations will be performed using SAS Version 9.4 or higher. Tables, 
listings, and figures will be presented in RTF format. Upon completion, all SAS 
programs will be validated by an independent programmer. In addition, all program 
output will undergo a senior level statistical review. The validation process will be used 
to confirm that statistically valid methods have been implemented and that all data 
manipulations and calculations are accurate. Checks will be made to ensure accuracy, 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 15 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
consistency with this plan, consistency within tables, and consistency between tables and 
corresponding data listings. Upon completion of validation and quality review 
procedures, all documentation will be collected and filed by the project statistician or 
designee. 
5.1 Conventions 
The precision of original measurements will be maintained in summaries, when possible.  
Means, medians and standard deviations will be presented with an increased level of 
precision; means and medians will be presented to one more decimal place than the raw 
data, and the standard deviations will be presented to two more decimal places than the 
raw data.  
 
Summaries of continuous variables that have some values recorded using approximate 
values (e.g., < or >) will use imputed values.  The approximate values will be imputed 
using the closest exact value for that measurement.  For tables where rounding is 
required, rounding will be done to the nearest round-off unit.  For example, if the round-
off unit is the ones place (i.e., integers), values ≥ XX.5 will be rounded up to XX+1 while 
values < XX.5 will be rounded down to XX.  
 
For percentages, unless they are calculated to be exactly 0% or 100%, values of very 
small or very large percentages will be reported as <0.1% and >99.9%. 
 
For frequency counts of categorical variables, categories whose counts are zero will be 
displayed for the sake of completeness.  For example, if none of the subjects discontinue 
due to “lost to follow-up” this reason will be included in the table with a count of 0.   
5.2 Standard Calculations 
Variables requiring calculation will be derived using the following formulas: 
 
 Baseline - A baseline value, unless specified otherwise, is the last non-missing 
value recorded prior to the first dose of study drug. If an assessment has both a 
date and time that exactly match the date and time of first dose of study drug, the 
assessment will be counted as baseline. 
 Study day – For a given date (date), study day is calculated as days since the date 
of first dose of study drug (firstdose): 
 
Study day = date – firstdose + 1, where date ≥ firstdose  
 
Study day = date – firstdose, where date < firstdose 
Study day 0 is defined as the day of study drug administration. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 16 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 Days – Durations, expressed in days, between one date (date1) and another later 
date (date2) are calculated using the following formula: duration in days = (date2-
date1+1). 
 Weeks – Durations, expressed in weeks, between one date (date1) and another 
later date (date2) are calculated using the following formula: duration in weeks = 
(date2-date1+1)/7. 
 Months – Durations, expressed in months, between one date (date1) and another 
later date (date2) are calculated using the following formula: duration in months = 
(date2-date1+1)/30.4375. 
 Years – Durations, expressed in years, between one date (date1) and another later 
date (date2) are calculated using the following formula: duration in years = (date2-
date1+1)/365.25.  
 Body Mass Index (BMI) - BMI (kg/m2) = weight (kg) / [[height (cm)/100]2] 
 Estimated Glomerular Filtration Rate (eGFR) -  
eGFR (mL/min/1.73 m2) = 175 × (serum creatinine in mg/dL)-1.154 × (Age in 
years)-0.203 × (0.742 if female) × (1.212 if African American).  
 
Note that age on consent date is collected on the CRF and will not be calculated. 
5.3 Handling Partial Dates for Adverse Events and Medications 
If only a partial date is available and is required for a calculation, the following standards 
will be applied: 
 
 Start dates  
a. 
For missing start day only - Day will be imputed as the first day of the 
month (i.e., 1) with the following exception: if the partial date falls in the 
same month and year as the date being used in the calculation (e.g., first 
dose date, informed consent date), then the partial date will be imputed to 
equal the date being used for the calculation. 
b. 
For missing start day and month - Day and month will be imputed as the 
first day of the year (i.e., 1 January) with the following exception: if the 
partial date falls in the same year as the date being used in the calculation 
(e.g., first dose date, informed consent date), then the partial date will be 
imputed to equal the date being used for the calculation. 
 
 Stop dates  
a. 
For missing stop day only - Day will be imputed as the last day of the 
month (i.e., 28, 29, 30, or 31)  


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 17 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
b. 
For missing stop day and month - Day and month will be imputed as the 
last day of the year (i.e., 31 December)  
 
A completely missing start date will be imputed as first dose date of study medication 
and a completely missing end date will be imputed as study completion date. 
The date of last dose of study drug will be taken from the Study Exit Status CRF page 
whenever available.  If this is missing, then the last visit date, excluding the follow-up 
visit, will be used, unless a blinded data review indicates it was earlier. 
 
Any partial dates will be displayed in data listings without imputation of missing days 
and/or months (e.g., MAR2016 for missing day, and 2015 for day and month both 
missing).   
5.4 Visit Windows 
Screening period is expected to happen at any time during 56 to 29 days before study Day 
0. Upon a successful screening visit, subjects will be enrolled and enter a run-in period of 
4 weeks from Day -28 to Day -1 to achieve a stable regimen with a common intranasal 
topical steroid (NASONEX [mometasone furoate monohydrate] 2 sprays in each nostril 
twice a day) while discontinuing any other intranasal topical steroid. 
 
Subjects’ qualifications will be tested once again before getting randomized into the 
study on Day 0. Subjects will be expected to be treated for 7 weeks (Day 0 to Day 49), 
followed by a follow up visits 5 and 9 weeks later (Days 84 and 112). During treatment 
phase a 2-day margin of error for each visit, and 4-day margin of error for each follow up 
visit will be acceptable.  
 
However, since study visits do not always take place exactly as scheduled in the protocol, 
it is necessary to assign the actual observation times to “analysis visit windows” for 
analysis purposes. Visit windows for each target visit are defined in Appendix A, and will 
be applied to all (safety, efficacy, etc.) measurements. For each summary and value if 
there are multiple values within a visit window, the “worst” value as defined in Appendix 
E will be used for that visit window summary except for all the efficacy endpoints where 
the rules are described in section 9. These visit windows will be applied to all visits, 
including scheduled, unscheduled, and early termination visits. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 18 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
5.5 Review of Blinded Data  
A number of analyses may require review of blinded data prior to database lock.  The 
following reviews may occur while the study is ongoing or prior to database lock. Subject 
ID will be masked in all of these reviews to avoid introducing any bias. 
 Concomitant medications are reviewed independent of Subject ID to identify 
prohibited meds 
 ECG data independent of Subject ID. 
 Review of adverse event summaries and listings to identify MedDRA preferred 
terms chosen are consistent with drug’s mechanism of action.   
 Review of protocol and consent deviations to identify major deviations that would 
exclude subjects from the per-protocol population. 
 Review of subjects with a missing or partial last dose date on the Study Exit 
Status CRF in order to determine an appropriate imputed date or other missing or 
partial dates for a parameter of interest; if deemed necessary. 
 Reasons for withdrawal which are potentially treatment related 
6. ANALYSIS POPULATIONS 
The following subject populations will be used for efficacy analyses:   
 
 Intent-to-Treat (ITT) population will include all randomized subjects. Treatment 
assignment will be based on the randomized treatment.  
 Modified Intent-to-Treat (MITT) population will include all randomized subjects 
who take at least one dose of the study drug and have both a baseline and at least 
one post-baseline efficacy assessment, but prior to the 4-week post-dose follow-
up assessment, for at least one of the following efficacy endpoints: TPS, PNIF, 
UPSIT, SNOT-22 or VAS.  
 Per-Protocol (PP) population will include all MITT population subjects who have 
a week 12 visit and valid efficacy measurements. Treatment assignment will be 
based on the randomized treatment. 
 Subjects will be included in their randomized stratum as reflected by the IXRS 
rather than eCRF. 
 
The Pharmacokinetic (PK) population will include any subject who received study drug 
and also had a post-dose PK sample drawn, defined as patients with serum concentration 
data obtained at pre-defined time points. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 19 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
The Safety population will include all randomized subjects who take at least one dose of 
study drug. Treatment assignment will be based on the treatment actually received. If a 
subject receives an incorrect treatment transiently, they will be assigned to the 
predominant treatment group (i.e., the treatment group for which they received the 
greater number of doses). 
 
Biomarker analyses will be performed in the Biomarker Population, defined as patients 
with at least 1 sample obtained for biomarker analysis.  
 
Should there be a for-cause reason to disqualify data from any non-compliant site, a 
Note-To-File letter, signed by the Sponsor, will be provided to InClin Biostatistics to do 
so. This Note-To-File letter should include description of the event/reason and an 
unbiased assessment of impact. A subset of the analyses will be run with and without this 
data to further assess the impact. 
7. STUDY POPULATION 
7.1 Subject Disposition 
Subject disposition information will be summarized for all subjects by treatment group, 
overall and by region, country and site.  Summaries will include: the number of 
randomized subjects, the number of subjects in each analysis population, the number of 
subjects completing the study (and subsets completing the study on and off treatment), all 
reasons for discontinuation of study drug and study, and the primary reason for 
discontinuation of study. 
 
The visit schedules and their timing are given in the table in Section 3 as given in Section 
4.2 of the protocol: 
 
A listing of all early discontinuations from study drug, as well as discontinuation from 
the study will be provided. 
7.2 Protocol Deviations 
In accordance with ICH E3, Sponsor-defined eligibility violations and post-
randomization protocol deviations will be identified and listed separately by study site 
and subject. Sources for these deviations may include IXRS, Trial Management or the 
clinical database. Deviations will be classified as follows (also see Appendix G): 
 
Deviation type/code as provided by Sponsor includes but is not limited to the following: 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 20 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 Informed consent 
 Randomization error  
 Safety 
 Efficacy 
 IP / Treatment deviation 
 Other protocol deviations  
 
Deviations are then categorized into: 
 Major 
 Minor 
 
A listing and tabulation of protocol deviations will be provided.  
7.3 Demographic and Baseline Characteristics 
Demographic variables to be summarized include the following: age at informed consent, 
gender, ethnicity, race, geographic region, height, weight, and body mass index (BMI). 
Height (in cm) and weight (in kg) will be measured at Screening, and BMI will be 
calculated. Weight will also be measured on Days 0 and 112 or ET.  
Demographic and baseline characteristics will be summarized for all the analysis 
populations (ITT, MITT, and Safety). Summaries will also be provided by region (US 
and non-US), for the MITT population. 
7.4 Medical History 
Verbatim terms on case report forms will be mapped to preferred terms and system organ 
classes using the Medical Dictionary for Regulatory Activities (MedDRA) (version 16.0 
or higher). 
 
The number and percentage of subjects with a given medical and/or surgical history will 
be summarized for each system organ class. Summaries will be provided for the Safety 
population. The verbatim and coded medical histories will be included in a listing. 
7.5 Physical Examinations 
A complete PE will be performed by either the Principal Investigator or a qualified 
Subinvestigator at Screening. A complete PE will include the following body system or 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 21 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
organ assessments: skin; head, eyes, ears, nose, and throat (HEENT); thyroid; lungs; 
cardiovascular system; abdomen; extremities; lymph nodes; and a brief neurological 
examination. Clinically significant findings will be documented. 
A symptom-directed PE, including assessments of possible infusion site reactions, will be 
performed by either the Investigator or a qualified Subinvestigator pre-dose on Days 0, 
21, and 49; and on pre- or post-dose on Days 14, 84 and 112 or ET. New abnormal PE or 
worsened findings will be documented by the Investigator or qualified Subinvestigator at 
the next scheduled visit. Whether physical exam was performed, along with body system 
and any clinically significant findings will be summarized by visit, and a detailed listing 
will be provided. 
Symptom directed physical exams will tabulate injection site reactions, corresponding 
AE if any, and whether it was worsened or rise to levels of clinically significant outcome. 
Physical and neurological examination results will be presented in by-subject listings.  
The results of complete physical and neurological examinations performed at screening 
will be summarized by body system. Evaluations based on the targeted examinations 
performed at subsequent visits will be summarized in a treatment-emergent fashion. For 
the physical examination, each body system is assessed as Normal or Abnormal, and if 
Abnormal, then Clinically Significant or Not Clinically Significant. For the neurological 
examination, each body system is assessed as Normal or Abnormal, and if Abnormal, 
then Clinically Significant or Not Clinically Significant. 
Summaries will present the number and percentage of subjects within each category by 
visit and by body system/parameter evaluated.   
7.6 Vital Signs 
Body temperature, supine systolic and diastolic blood pressure, pulse, and respiratory rate 
will be measured at Screening and on Days -3, 0, 14, 21, 49, 84, and 112 or at ET. On 
Days 0, 21, and 49, vital signs will be measured pre-dose, and every 15 minutes after the 
start of infusion, as well as immediately following the end of infusion. All vital signs will 
be measured after the patient has been in the supine position for ≥5 minutes. These 
measurements include systolic and diastolic blood pressure, pulse rate, respiratory rate, 
and body temperature. 
7.7 ECG 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 22 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
12-Lead ECG will be collected only at screening between Days -56 to -29. Mean heart 
rate, RR, PR, QRS, QTcB and QTcF along with abnormalities will be summarized and a 
listing will provide more detailed by-subject data. 
7.8 Fecal Collection 
Fecal samples will be collected at Screening for ova and parasite tests. 
7.9 Adverse Events 
Information regarding AEs will be obtained from the time of the first study drug 
administration until completion of the last study-related procedure (Day 112 or ET). 
Information regarding serious adverse events (SAEs) will be obtained from the time the 
patient signs an ICF until completion of the last study-related procedure (Day 112 or ET). 
Duration (start and stop dates and times), severity, outcome, treatment, and relation to 
study drug will be recorded on the eCRF. 
7.10 Laboratory Values 
Serum pregnancy (at Screening and Days -3, 21, 49 and 112 or ET), hematology and 
chemistry (at Screening, Days -3, 14, 21, 49, 84, and 112 or ET), and urinalysis (at 
Screening, Days -3, 14, 49, 84, and 112 or ET) laboratory results will be collected, listed 
by subject and visit, and tabulated by visit for each parameter. 
7.11 Anti-Drug Antibody (ADA) 
Blood will be collected for determination of ADA pre-dose on Day 0 and, should a 
related AE suspected of being associated with immunogenicity occur, post-dose, as well 
as on Day 112 or ET. Should these results be available at the time of developing the 
TLFs, a summary and listing will be provided. 
7.12 Prior and Concomitant Medications 
Verbatim terms on case report forms will be mapped to Anatomical Therapeutic 
Chemical (ATC) class and Generic Drug Names using the World Health Organization 
(WHO) dictionary (WHODDE B2, March 1, 2015 release or higher). 
Prior and concomitant medications include both prescribed and over-the-counter 
medications. Prior medications are those medications started within the 30 days before 
Screening. Concomitant medications are those medications taken at the start of study 
drug or initiated after the initial dose of study drug. Prior medications and concomitant 
medications will be summarized separately for each treatment by WHO ATC level 1 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 23 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
term, ATC level 3 term and Preferred Term (generic name) with frequency and 
percentage of subjects in each dosing arm using each prior medication and each 
concomitant medication. At each level of subject summarization, a subject is counted 
once if he/she reported one or more medications at that level. Each summary will be 
ordered alphabetically by each level of ATC class and generic drug name within each 
level of ATC class. Prior and Concomitant medications will also be listed separately with 
these elements as well as the verbatim drug name.  
The overall summary and subsets of concomitant medications will be provided for all the 
analysis populations. The summary of prior medications will be provided only for the 
Safety Population. 
8. EFFICACY ANALYSES 
The primary efficacy analysis will be based on the MITT population. Additional 
supportive efficacy analyses will be performed using the PP population.  Selected 
sensitivity analyses will be performed using the ITT population. 
8.1 Efficacy Variables 
8.1.1 Primary Efficacy Variable 
The primary endpoint of this study is the reduction in TPS values from Baseline to Week 
12 after the start of treatment. Polyps will be evaluated in each nostril by means of nasal 
endoscopy and graded based on polyp size, resulting in scores of 0 to 4 as indicated in  
Appendix F. The TPS is the sum of the left and right nostril scores. The TPS values for 
efficacy analyses will be determined from blinded central evaluations of nasal 
endoscopies performed at Screening, on Day -3, pre-dose on Days 21 and 49, and on 
Days 84 and 112 or ET. Videos of the endoscopies will be evaluated by independent 
blinded reviewer.  
8.1.2 Secondary Efficacy Variables 
The following secondary clinical endpoints will be evaluated from Baseline to Week 12 
after the start of treatment on changes in: 
 Size of polyps as evaluated by Lund-Mackay score (in Appendix F) at selected 
Investigator sites by CT scan on Days -3 and 84 or ET 
 Nasal airway patency as evaluated by PNIF pre-dose on Days 0 and 21 and on 
Days 84 and 112 or ET 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 24 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 Ability to smell by UPSIT (in Appendix F) pre-dose on Days 0, 21, and 49 and on 
Days 14, 84, and 112 or ET   
 Patient-reported symptoms of sinusitis by SNOT-22 (in Appendix F) pre-dose on 
Days 0, 21, and 49, and on Days 14, 84, and 112 or ET and VASs on Day -3, pre-
dose on Days 0, 21, and 49; and on Days 14, 84, and 112 or ET  
 Clinical symptoms improvement scale (in Appendix F) on Day -3, pre-dose on 
Days 0, 21, and 49; and on Days 14, 84, and 112 or ET  
 Quality of life by SF-36 (in Appendix F) pre-dose on Days 0, 21, and 49 and on 
Days 84 and 112 or ET   
 
The secondary efficacy variables also include the following: 
 Time to first response in TPS 
 Change in TPS, UPSIT, and patient-reported symptoms of sinusitis over time 
 Safety and tolerability of each of 2 doses of AK001 separately in combination 
with an INS  
8.1.3 Exploratory Efficacy Variables 
Several exploratory analyses are pre-specified (additional post hoc analyses may be 
performed):  
 
In all patients, to  
 Potentially explore markers of MCs and eosinophils and inflammatory response in 
blood 
 
In patients with comorbid asthma, to explore the effect of each of 2 doses of AK001 
separately in combination with an INS versus the INS alone on changes from Baseline to 
Week 12 after the start of treatment in: 
 TPS 
 Pulmonary function (forced expiratory volume in 1 second [FEV1], forced vital 
capacity [FVC], and forced expiratory flow [FEF]) assessed using spirometry 
(from Baseline to Week 7) 
 Asthma-related symptoms (Asthma Control Test™ [ACT]) in Appendix F 
 Use of asthma rescue therapy 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 25 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
8.2 Adjustments for Covariates 
The models for analyses of the primary endpoint (change in TPS) will include the 
treatment group, time, interaction between treatment group and time. 
 
Also, all analyses will include presence or absence of asthma as the only stratification 
variable in the model. 
8.3 Handling of Dropouts or Missing Data 
The occurrence of missing data could potentially lead to bias and misleading conclusions. 
Therefore, strenuous efforts and plans are in place to obtain all scheduled efficacy 
assessments from all randomized subjects, regardless of whether or not they remain on 
study treatment. In addition, multiple sensitivity analyses will be performed to examine 
robustness of the results of the pre-specified primary analyses. These sensitivity analyses 
will be described in greater detail in later sections of this document.  
8.4 Interim Analysis and Data Monitoring 
No interim analyses are planned for evaluating efficacy. However interim safety 
monitoring will be performed according to the DMC charter. 
8.5 Examination of Subgroups 
Subgroup analyses are to be performed for the primary and the exploratory efficacy 
variables with subjects categorized by the presence of asthma. If adequate data is 
available, gender (male, female),  and age (<median, ≥median) will be used as covariates 
as well. 
8.6 Multiple Comparisons/Multiplicity  
Each active treatment group will be compared separately with the placebo group by 
utilizing a mixed effect repeated measures analysis of variance (ANOVA) model with 
specific contrast statement for Week 12 as well as other time points for each comparison 
separately. Adjustment in alpha for multiple comparisons will be controlled according to 
the Hochberg method, in which, if the efficacy comparison of the high active arm versus 
placebo is statistically significant at the 0.05 level, no penalty will be assessed to the 
comparison of low active arm versus placebo. Otherwise, the low active arm versus 
placebo will be compared at the 0.025 level. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 26 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
8.7 Multicenter Studies 
The study will be conducted at approximately 14 investigational sites in the European 
Union and the United States, and approximately 70 patients will be enrolled.  
 
Because the study will include a large number of study sites, relative to the total number 
of subjects, the effect of study site will not be included in the statistical analysis models. 
However if a highly influential site is identified, the differences between treatment 
groups will be examined with and without the influential site.  
 
9. METHODS OF EFFICACY ANALYSIS 
For all efficacy analyses, if there are multiple values within a visit window, the on-
treatment value whose date is closest to the scheduled date shall be used for the summary. 
In the case that more than one on-treatment value is equidistant from the scheduled date, 
the later will be used. 
9.1 Primary Efficacy Analyses 
There are therefore three primary null hypotheses to consider: 
H01:  There is no difference between AK001 (250 mg or 25 mg) in combination with 
NASONEX and NASONEX alone in reduction in size of nasal polyps as evaluated 
by the change from Baseline to Week 12 in TPS 
H02:  There is no difference between AK001 250 mg (high dose) in combination with 
NASONEX and NASONEX alone in reduction in size of nasal polyps as evaluated 
by the change from Baseline to Week 12 in TPS 
H03:  There is no difference between AK001 25 mg (low dose) in combination with 
NASONEX and NASONEX alone in reduction in size of nasal polyps as evaluated 
by the change from Baseline to Week 12 in TPS 
The primary analyses will be based on the MITT population, defined as all subjects 
randomized who receive at least 1 dose of study drug and have a valid Baseline 
measurement and at least 1 post-baseline efficacy assessment. Subjects will be analyzed 
for efficacy according to the group to which they were randomized.  
 
The primary analysis specification refers to “number of subjects retained at week 12”  
where “number of subjects retained at visit X” is defined as follows: If a subject has an 
on-treatment assessment with a non-missing score for any of efficacy measurements at 
visit X, or at any scheduled visit subsequent to X, then this subject is defined to be 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 27 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
retained at visit X. Otherwise the subject is defined to be not retained at visit X. Note that 
this is a per-subject definition, not a per-endpoint definition. 
 
The effect of each of 2 doses of AK001 separately in combination with an INS versus the 
INS alone on the reduction in size of nasal polyps as evaluated by the change from 
Baseline to Week 12 after the start of treatment in TPS will be displayed for each 
treatment group by study visit using summary statistics, including the number of 
observations, the mean, median, standard deviation (SD), and range (min, max).  Each 
active treatment group will be compared separately with the placebo group for change 
from Baseline in TPS by using a mixed effect repeated measures analysis of variance 
(ANOVA) model with specific contrast statement for Week 12 and for each comparison 
separately. Adjustment in alpha for multiple comparisons will be controlled according to 
the Hochberg method, in which, if the efficacy comparison of the high active arm versus 
placebo is statistically significant at the 0.05 level, no penalty will be assessed to the 
comparison of the low active arm versus the placebo arm. Otherwise, the low active arm 
versus the placebo arm will be compared at the 0.025 level. 
 
The dependent variable will be the change from baseline in TPS (blinded centralized 
nasal endoscopy score) at Week 12. The mixed model, as the primary analysis of the 
primary endpoint, will include fixed effects for treatment group (three levels), asthma 
(two levels: presence versus absence), and baseline TPS score. The Kenward and Roger 
method of calculating the denominator degrees of freedom will be used for the tests of 
fixed effects. Treatment comparisons to placebo will be established using contrast 
statements at Week 12.  
9.2 Sensitivity Efficacy Analyses of Primary Endpoints 
9.2.1 Analysis for TPS in Presence of Missing Data 
Because the occurrence of missing data could potentially lead to bias, strenuous efforts 
will be made to obtain all scheduled efficacy assessments from all randomized subjects, 
regardless of whether or not they remain on study treatment.  
                                                                                                                                                                                                           
Missing values will be imputed by replacing the missing value with the average value of 
the placebo group at the specific time point  
At the conclusion of imputation of the missing data, the same identical analysis as 
described for the primary endpoint (Section 9.1) will be once again conducted to examine 
the robustness of the outcome. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 28 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
9.2.2 The Analysis with TPS including Time as a Repeated Factor 
The dependent variable will be the change from baseline in TPS (blinded centralized 
nasal endoscopy score) at Week 12. The mixed model, as the primary analysis of the 
primary endpoint, will include fixed effects for treatment group (three levels), asthma 
(two levels: presence versus absence), time (weeks 0, 3, 7, 12, and 16[ET]) in which case, 
baseline TPS and subject as random effects (using SAS Repeated statement), and the 
interaction between treatment effect and time may be included in the model. The 
Kenward and Roger method of calculating the denominator degrees of freedom will be 
used for the tests of fixed effects. Treatment comparisons to placebo will be established 
using contrast statements at Weeks 2, 3, 7, 12 and 16.  
9.2.3 Analysis of TPS in Absolute Value and Percent Change from Baseline 
Additional efficacy measures will be analyzed in support of the primary efficacy 
endpoint results. In addition to change from Baseline in TPS, absolute values and 
percentage changes from Baseline will be analyzed separately using the same repeated 
measures model described above (Section 9.2.2). 
9.2.4 Alternate Analysis Population 
The primary efficacy analyses of TPS will be repeated using the ITT and Per Protocol 
population based on similar models described in Sections 9.1 and 9.2.2.  
 
9.2.5 Time to Response 
Time to response will be compared between all 3 treatment groups by summarizing 
number and number (%) of subjects with response, Mean, Standard Deviation, Range, 
and Median time to response for those with response. In addition, time to response will 
be analyzed using Kaplan-Meier curve supplemented by the Cox Proportional hazard 
model to estimate both the median and HR comparing across the groups.  
 
Response will be defined for each of the following endpoints: TPS, PNIF, UPSIT, 
SNOT22, and VAS as 50% reduction from baseline. For TPS only, responders will be 
also defined as those with 1-point reduction from baseline. Kaplan-Meier method and 
Cox PH model will be utilized to analyze time to first response. The 25th, 50th (Median) 
and 75th percentiles will be provided by treatment/dose group along with “survival” 
curves, 95% confidence interval and log-rank test p-value. In addition, HR, its 95% 
confidence interval and the associated p-value will be also presented. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 29 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
9.2.6 Subgroup Analyses 
Subgroup analyses are to be performed for the primary efficacy variable using repeated 
measures analysis of variance for the following subgroups:  
 Comorbid asthma (to be defined on the presence or absence of asthma) 
o Yes 
o No  
 Age  
o < Median 
o ≥ Median 
 Gender 
o Male 
o Female 
 Response (responders are defined as subjects with 50% or 1-point reduction in 
total TPS score) 
o Yes 
o No 
9.3 Secondary Efficacy Analyses 
The primary population for secondary efficacy analyses will be the MITT population.  
 Size of polyps, as evaluated by Lund-Mackay score at selected Investigator sites 
by CT scan (CT scans are optional and will only be done at Investigator sites at 
which appropriate and timely regulatory approval or authorization can be 
granted) (Appendix F) will be measured for six different components of the 
system, each with possible score of 0=absence; 1=partial opacification; and 
2=complete opacification - with a total score of 0 to12. Descriptive statistics will 
be provided by treatment groups for each component of the system and the total 
score. Change from baseline in total score will be compared between each of the 
high and low dose AK001 and Placebo using an ANOVA model.     
 Change from baseline in PNIF will be compared across the groups using a similar 
repeated measure ANOVA as described before. Contrast statements will be built 
to highlight differences at Weeks 3, 12 and 16. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 30 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 UPSIT (Appendix F): Descriptive statistics of scoring correct answers (Out of 40 
possible correct answers) will be provided by treatment groups. Should it be 
feasible, score for each odorant will be listed along with the total score.  The 
UPSIT total score will be compared between the groups using a repeated measure 
ANOVA with contrast statements for comparison at week 12 as well as other 
time points in the study. It is expected that each subject will respond to each of 
the Odorants. Missing data will be assumed to be a wrong response and no 
imputation will be performed to replace.  
 Patient-reported SNOT-22 (Appendix F): Five most important items will be 
listed and summarized for each treatment group. Change from baseline in total 
score of the five most important items, as well as all items, will be compared 
between the treatment groups over time using repeated measure ANOVA 
described before. Contrast statements will be included to compare high and low 
dose AK001 to placebo at different visits. The missing answers will be imputed 
by average score of the items present. In other words, missing values will be 
imputed by the total score divided by the total number of non-missing items with 
value.            
 VAS scale of 0-10 (Appendix F): For each of the five symptoms of rhinosinusitus 
(Anterior nasal discharge, Posterior nasal discharge, Nasal congestion, blockade, 
or obstruction, Decreased sense of smell, and Facial pain or pressure), VAS 
scores will be categorized into mild (0,1,2), moderate (3,4,5,6), and severe 
(7,8,9,10). Number (%) of subjects in each category will be summarized by 
treatment group. Change from baseline (Week 0) to each visit for each VAS 
score from different symptoms will be computed and compared across the 
treatment groups using a repeated measure ANOVA with contrast statements as 
described before. Change from baseline in individual symptoms as well as the 
total VAS score across all symptoms will be analyzed similarly. Missing VAS 
score will be imputed by average of the non-missing values.           
 Clinical symptoms improvement scale (Appendix F):  Change from baseline in 
VAS (0-10) Clinical Symptoms Improvement Scale will be compared over time 
across the treatment groups using a repeated measures ANOVA model with 
contrast statements at each visit.  
 SF-36 (Appendix F): Change from baseline in total SF-36 score will be compared 
over time across the treatment groups using a repeated measures ANOVA model 
with contrast statements at each visit. Missing item values will be imputed by the 
average score of the category that the question belongs to. These categories are 
groups of questions with 3, 5 and 6 possible responses as indicated in Appendix 
F.  


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 31 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
9.4 Exploratory Efficacy Analyses 
Markers of MCs and eosinophils and inflammatory response in blood will be summarized 
descriptively by mean, median, standard deviation, min and max across groups.  
 
In the subgroup of patients with comorbid asthma, the following analyses will be 
conducted: 
 Use of asthma rescue therapy summarized by number and percentage. Change 
from baseline to Week 12 will be displayed using a shift table. Scoring the rescue 
medication question ACT4 by 4, 3, 2, 1, and 0 to perform change from baseline 
comparison between groups 
 Change from screening in pulmonary function as evaluated by FEV1 , FVC, and 
FEF (could be expiratory volume or percentage of lung capacity) will be 
compared across treatment groups using the same repeated measures ANOVA 
model described earlier.  
  Change from baseline in total ACT score will be compared over time across the 
treatment groups using a repeated measures ANOVA model with contrast 
statements at each visit. The missing answers will be imputed by average score of 
the non-missing values as described earlier.        
 
9.5 Pharmacokinetic And Biomarker Analyses 
A listing of concentration data and time of sample collection relative to dosing will be 
generated. Pharmacokinetic parameters will be estimated using non-compartmental 
methods and compared across the groups using an ANOVA model. Baseline covariates 
may be added to the model as needed. 
 
At selected investigator sites, biomarkers related to eosinophilic and mast cell (MC) 
inflammation will be evaluated in nasal secretions and blood samples collected at Days -
3, 14, 21, 49, and 112 or Early Termination (ET) from patients who consent to participate 
in the analysis. For each biomarker (ECP, histamine, tryptase, prostaglandins, 
leukotrienes, chymase, carboxypeptidase A3, cytokines, chemokines, and growth 
factors), the following analyses will be performed:  
 Changes from Baseline to Week 16 after the start of treatment:   


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 32 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
The effect of 2 different dose levels of AK001 separately in combination with 
INS versus the INS alone on each of biomarkers as evaluated by change and 
percent change from baseline to Week 12 after the start of treatment will be 
displayed for each treatment group by study visit using summary statistics, 
including the number of observations, the mean, median, standard deviation (SD), 
and range (min, max).  The AK001 25 mg and 250 mg subjects will be compared 
to placebo according to a mixed effect repeated model which will include 
treatment, stratification factor (comorbid asthma; if feasible),  and baseline as 
covariates. Each active treatment group will be compared separately with the 
placebo group for change and percent change from baseline using a similar model 
if data permits.        
 Effects over time:  
The change and percent change from baseline over time for AK001 25 mg and 
250 mg subjects will be compared to placebo according to a repeated measured 
mixed effect model which will include treatment, stratification factor (comorbid 
asthma; if feasible), time (weeks 2, 3, 7, and 16[ET]), baseline, and the interaction 
(if feasible) between treatment and time. Treatment comparisons to placebo will 
be established using contrast statements at Weeks 2, 3, 7, and 16. If adequate data 
exists, the same analysis will be repeated to compare each AK001 dose level to 
placebo. The estimated LS mean and standard error of change and percentage 
changes from Baseline over time will be plotted.  
            
10. SAFETY ANALYSES 
All safety analyses will be based on the Safety population.  
 
Safety and tolerability will be assessed throughout the study by monitoring and 
evaluating TEAEs, including any complications resulting from the IV infusion, and 
changes in vital signs and in clinical safety laboratory test (including ADA) and PE 
findings. All safety and tolerability endpoints will be summarized by treatment. Baseline 
for all safety endpoints will be defined as the last recorded observation before the 
administration of the IV infusion of study drug. Safety measures, including AEs, clinical 
safety laboratory tests (including ADA), vital signs, PEs, and concomitant medication 
usage, will be summarized descriptively. For quantitative variables, descriptive statistics, 
including number of observations, means, medians, SDs, and ranges, will be provided for 
the values themselves as well as for the changes from Baseline by treatment group at 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 33 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
each study visit. Qualitative variables will be summarized using counts and percentages 
in each treatment group at each study visit. 
10.1 Adverse Events 
Adverse events will be coded to System Organ Class (SOC) and preferred term using 
MedDRA (version 16.0). The coding process is described in the Data Management Plan.   
 
The tabular summaries will be provided for AEs, with the number and percentage of 
subjects reporting each type of event presented by each treatment group and placebo. If a 
subject reports the same preferred term more than once, it is counted only once within 
that category. Further, for a given tabulation, the preferred term will only be counted 
once at its worst severity and strongest relationship to treatment. 
Adverse events will be regarded as treatment-emergent (TEAE) if they start on or after 
the time of first dose of study drug administration or if they were present prior to the first 
dose of study drug administration and increased in severity or relationship to study drug 
while on study drug.   
 
The following summaries for TEAEs will be provided: 
 
 An overall summary table of TEAEs by SOC and preferred term.   
 Subject incidence of TEAEs by maximum severity, SOC, and preferred term. 
 Subject incidence of TEAEs by MedDRA SOC, preferred term, and strongest 
relationship to study drug (Related/Not Related). Events reported as “Possibly 
Related,” or “Related” will be included in the Related category. Events reported 
as “Unlikely Related” or “Not Related” will be included in the Not Related 
category. At each level of subject summarization a subject is classified according 
to the strongest relationship, as determined by the investigator, if the subject 
reported one or more events. AEs with a missing relationship will be considered 
related for this summary. 
 Subject incidence of TEAEs leading to withdrawal by SOC and preferred term. 
 Subject incidence of serious TEAEs (SAEs) by SOC and preferred term 
All AEs will be collected starting from the first study drug administration through Day 
112 or ET. Severity will be assessed by the Investigator using the protocol-defined 
grading scales (Section 11.1). All AEs will also be judged by the Investigator as to 
whether they are clinically significant and related to study drug. 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 34 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Post-treatment AEs are defined as the subset of TEAEs that have an onset more than 
7 days after the last dose of study drug or that worsen in intensity or treatment attribution. 
A summary of post-treatment adverse events by MedDRA system organ class and 
preferred term will be provided along with a flag in the overall listing.  
 
Summaries for subsets of TEAEs of interest (Allakos AE Groupings) and planned 
subgroup analyses (e.g., by demographics) are described in the sections following. 
 
All AEs will be presented in a data listing. In addition, listings will also be provided for 
SAEs (including subsets for fatal and non-fatal SAEs), AEs leading to dose reduction 
and/or interruption, AEs leading to discontinuation of study drug, and AESIs.  
10.1.1 Selected Subsets of Adverse Events 
There are no known adverse events of special interest. Should any be noted during the 
study, they will be flaged in the listings.  
10.1.2 Subgroup Analyses 
The summaries of Allakos AE groupings described in Section 10.1.1, as well as the most 
common TEAEs (occurring in more than 20% in any treatment group), will be repeated 
for the following subgroups of subjects: 
 Asthma: presence/absence 
 Age group: < median and  ≥ median  
 Gender: male/female 
 
Other subgroup analyses of interest may be identified during data review (e.g., based on 
concomitant medications or medical conditions). 
10.2 Clinical Laboratory Evaluation 
Safety laboratory tests include serum chemistry, hematology, urinalysis and ADA 
findings.  
 
Central laboratory data are transferred electronically by Covance. The Data Transfer 
Specification document provides a detailed description of the content and format of the 
laboratory datasets. Both conventional units and International System of Units (SI) are 
provided and will be summarized in separate tables and listings. The eGFR values will be 
calculated using the formula provided in Section 5.2 and will be included in the tables 
and listings for clinical chemistry parameters. Results from local laboratories are entered 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 35 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
into the CRF by the site; these will not be included in summary tabulations but will be 
included in the data listings together with the corresponding normal ranges. Values for 
local laboratory parameters will be converted to the corresponding alternative units, 
either conventional or SI, depending on how reported.  
 
For the summary tabulations of laboratory results, Baseline is defined as the last non-
missing value prior to first dose of study drug. Laboratory tests obtained on the date of 
the first dose will be assigned to pre-treatment; the relative times of blood sampling and 
dosing will be checked programmatically to confirm this assumption. For each analyte, 
Baseline values will be restricted to those subjects in the safety population for whom 
there is at least one post-Baseline value (either overall or for the corresponding target 
visit).  
 
Visit windows are used when results are presented by target visit (see Appendix A).  For 
each analyte, if a subject has multiple values within a visit window, the “worst” value as 
defined in Appendix E will be used for that visit window summary. 
 
Descriptive statistics will be used to summarize continuous laboratory results at Baseline, 
each post-baseline visit, and the change from Baseline for each visit; the last available 
on-treatment value will also be summarized. For each visit, changes from baseline will 
also be summarized by n (%), Mean, Median, SD and (Min, Max) for continuous 
laboratory parameters.  In addition, continuous laboratory parameters will be summarized 
by shift table according to changes from Baseline relative to the reference range (low, 
normal, high) at Baseline and each post-baseline time point. Missing n (%) will be 
indicated in all tables.   
 
Categorical laboratory parameters will be summarized by treatment group for each target 
visit using counts and percent of subjects in each category. A shift table will also be 
presented for categorical parameters. Missing categories will be included in the shift 
tables. 
 
Thresholds for potentially clinically significant (PCS) laboratory abnormalities are 
defined in Appendix B for selected parameters. When there are thresholds provided for 
low and high values, they will be handled separately. Summaries will include the number 
and percent of subjects with treatment-emergent PCS values, restricted to those subjects 
in whom the values represent a post-Baseline worsening (PCST); the number meeting 
criteria at Baseline will also be summarized. A PCST is defined as any PCS event that 
happened at any post-Baseline visit and has a value more out of range than the value for a 
particular test at Baseline (see Appendix E for directionality of worsening). 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 36 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Listings of laboratory parameter results will be presented. Listings will include all 
laboratory flags provided by the central laboratory in the data transfer as well as flags for 
those that meet criteria for being PCS (whether or not a treatment-emergent worsening); 
additionally, results evaluated by the investigator as abnormal/clinically significant will 
be flagged in the listing.  
 
Separate listings for each hematology, chemistry, and urinalysis parameter will include 
only subjects with treatment-emergent PCS values and, for these subjects, all laboratory 
results for the parameter meeting PCS criteria and related parameters (e.g., ALT, AST, 
bilirubin, neutrophils, WBC, etc.) will be provided.  
10.3 Vital Signs 
For the summary tabulations of diastolic blood pressure, systolic blood pressure, pulse 
rate, temperature, and respiratory rate at baseline, baseline will be defined as the last non-
missing value prior to the first dose of study drug. Pre-dose and post-dose (target 2 hours 
post-dose for seated and standing blood pressure and pulse and hourly for at least 4 hours 
for temperature and respiratory rate) in each parameter will be summarized using 
descriptive statistics. Change from baseline in these vital signs will also be calculated and 
summarized.  
 
Vital sign measurements subsequent to Day 0 will be summarized descriptively by target 
visit using the visit windows defined in Appendix A and the last available on-treatment 
visit; These include seated blood pressure and pulse, temperature, respiratory rate, and 
body weight. If a subject has multiple values within a visit window, the “worst” value as 
defined in Appendix E will be used for that visit window summary.  
 
Potentially clinically significant vital sign changes are defined for selected parameters in 
Appendix C. When there are thresholds provided for low and high values, they will be 
handled separately. Summaries will include the number and percent of subjects with 
treatment-emergent PCS values, restricted to those subjects in whom the values represent 
a post-Baseline worsening (PCST). A PCST is defined as any PCS event that happened at 
any post-Baseline visit and has a value more out of range than the value for a particular 
parameter at Baseline (see Appendix E for directionality of worsening). 
 
Listings of vital sign measurements including height at Screening will be presented. 
Listings will flag results that meet criteria as being PCS (whether or not a treatment 
emergent worsening).  
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 37 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Separate listings for each vital sign parameter will include only subjects with treatment-
emergent PCS values and, for these patients, all corresponding vital sign results will be 
provided. 
10.4 Prior and Concomitant Medications  
Prior and concomitant medications will be summarized by ATC Class 1, ATC Class 3, 
and preferred term throughout the whole study.  
 
11. CHANGES TO PROTOCOL-SPECIFIED ANALYSES 
Changes made to the SAP after it has been signed but prior to database lock will be 
documented in an amendment. Any important changes made to the analysis and required 
in response to data review, will be described in the Clinical Study Report (CSR).  
 
12. REFERENCES 
1. Hedman J, Kaprio J, Poussa T, Nieminen MM. Prevalence of asthma, aspirin 
intolerance, nasal polyposis and chronic obstructive pulmonary disease in a 
population-based study. Int J Epidemiol 1999;28(4):717-22. 
2. Mygind N, Dahl R, Bachert C. Nasal polyposis, eosinophil dominated inflammation, 
and allergy. Thorax 2000;55 Suppl 2:S79-83. 
3. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European 
Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl 2012(23):3 p 
preceding table of contents, 1-298. 
4. Pearlman AN, Chandra RK, Conley DB, Kern RC. Epidemiology of nasal polyps. In: 
Nasal Polyposis, eds. T.M. Onerci and B.J. Ferguson. Springer-Verlag: Berlin 
Heidelberg 2010. In. 
5. Bachert C, Gevaert P, Holtappels G, Johansson SG, van Cauwenberge P. Total and 
specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy 
Clin Immunol 2001;107(4):607-14. 
6. Kiwamoto T, Kawasaki N, Paulson JC, Bochner BS. Siglec-8 as a drugable target to 
treat eosinophil and mast cell-associated conditions. Pharmacol Ther 
2012;135(3):327-36. 
7. US Department of Health and Human Services. Common Terminology Criteria for 
Adverse Events Version 4.0. 28May2009. Available from: 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf. Accessed 01Feb2016. 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 38 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 39 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
APPENDICES 
Appendix A:  Visit Windows 
The visit windows do not apply to the follow-up visits, which are always assigned as 
follow-up, regardless of when they occur.  Unscheduled and early termination visits are 
included in the windowing algorithm. 
 
Visit windows for efficacy assessments  are defined in the following table. In case of 
multiple values, the one closest to the intended collection time will be chosen. 
 
Window Label 
Time Interval (Study Day[1]) 
Scheduled Day 
Screening 
-56 to -29 
-42 
Run-in 
-28 to -1 
-14 
Day 0 Predose 
0 
0 
TP: Day 0 
0 to 3 
0 
TP: Week 2 
4 to 17 
14 
TP: Week 3 
18 to 35  
21 
TP: Week 7 
36 to 63 
49 
FU: Week 12 
64 to 98 
84 
FU: Week 16 
≥99 
112 
FU: Week 24[2] 
Not Applicable to efficacy 
Not Applicable to efficacy 
[1] Calculated as in Section 5.2. 
[2] Week 24 applies to safety data in UK and Germany only, with no impact on 
efficacy.  
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 40 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Appendix B:  Criteria for Determining Potentially Clinically Significant Values in 
Laboratory Test Results 
Test 
Criteria - System 
International Units 
Criteria – 
Conventional Units 
Hemoglobin 
Female: ≤ 95 g/L;  
Male: ≤ 115 g/L;  
Decrease of ≥ 20% 
Female: ≤ 9.5 g/dL; 
Male: ≤ 11.5 g/dL; 
Decrease of ≥ 20% 
Hematocrit 
Female: ≤ 0.32; Male: ≤ 
0.37  
Female: ≤ 32%;  
Male: ≤ 37% 
WBC count 
≤ 2.8 × 109/L 
≥ 16 × 109/L 
≤ 2800/µL or ≥ 
1600/µL 
Neutrophils 
≤ 1.0 × 109/L  
≤ 1000/µL 
Eosinophils 
≥ 0.7 × 109/L 
≥ 700/µL 
Platelet count 
≤ 75 × 109/L  
≥ 700 × 109/L 
≤ 75 × 103/µL 
≥ 700 × 103/µL 
Sodium 
<130 mmol/L  
>150 mmol/L 
<130 mEq/L 
>150 mEq/L 
Potassium 
< 3.0 mmol/L  
> 5.5 mmol/L 
< 3.0 mEq/L 
> 5.5 mEq/L 
Calcium 
< 1.75 mmol/L  
> 3.00 mmol/L 
< 7.00 mg/dL 
> 12.00 mg/dL 
Triglycerides, 
fasting/nonfasting/unknown 
> 3.39 mmol/L 
> 300 mg/dL 
Glucose, 
fasting/nonfasting/unknown 
< 2.775 mmol/L  
>13.875 mmol/L 
< 50 mg/dL 
> 250 mg/dL 
Uric acid 
Female: >475.8 µmol/L; 
Male: >594.8 µmol/L 
Female: > 8 mg/dL; 
Male: >10 mg/dL 
Albumin 
<25 g/L 
<2.5 g/dL 
Total bilirubin 
≥ 34.2 µmol/L 
≥ 2 mg/dL 
ALT 
≥ 3 × ULN 
≥ 3 × ULN 
AST 
≥ 3 × ULN 
≥ 3 × ULN 
Alkaline phosphatase 
≥ 3 × ULN 
≥ 3 × ULN 
TpI 
>ULN  
>ULN 
Methemoglobin 
>3.5% 
>3.5% 
BUN  
> 17.85 mmol/L 
> 50 mg/dL 
Creatinine 
≥ 177 µmol/L 
≥ 2 mg/dL 
Cholesterol 
>10.36 mmol/L 
> 400 mg/dL 
CK 
≥ 3 × ULN 
≥ 3 × ULN 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 41 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Test 
Criteria - System 
International Units 
Criteria – 
Conventional Units 
GGT 
≥ 3 × ULN 
≥ 3 × ULN 
LDH 
≥ 3 × ULN 
≥ 3 × ULN 
Phosphorus 
< 0.646 mmol/L  
> 1.777 mmol/L 
Low: <2.0 mg/dL 
High: >5.5 mg/dL 
Urinalysis – Protein 
Increase of ≥ 2 units 
Increase of ≥ 2 units 
Urinalysis – Glucose 
Increase of ≥ 2 units 
Increase of ≥ 2 units 
Urinalysis – Blood 
Increase of ≥ 2 units 
Increase of ≥ 2 units 
Urinalysis – Bilirubin 
Increase of ≥ 2 units 
Increase of ≥ 2 units 
ULN = Upper Limit of  Normal 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 42 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Appendix C:  Criteria for Determining Potentially Clinically Significant Values in 
Vital Signs 
Test 
Criteria 
Systolic Blood Pressure 
(SBP) – Seated (mmHg) 
Increase of ≥ 20 mmHg from baseline and > 180 
mmHg 
Decrease of ≥ 20 mmHg from baseline and < 90 mmHg 
Diastolic Blood Pressure 
(DBP) – Seated (mmHg) 
Increase of ≥ 15 mmHg from baseline and > 105 
mmHg 
Decrease of ≥ 15 mmHg from baseline and <50 mmHg 
Pulse – Seated (beats/min) 
Increase of ≥ 15 beats/min from baseline and > 120 
beats/min 
Decrease of ≥ 15 beats/min from baseline and < 50 
beats/min 
Temperature 
Increase of ≥ 2.0oC from baseline and > 38.0oC 
Decrease of ≥ 2.0oC from baseline and < 36.0oC 
Weight 
Decrease of ≥ 7% from baseline 
Decrease of ≥ 10% from baseline 
Increase of ≥ 7% from baseline 
Increase of ≥ 10% from baseline 
 
 
 
 


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 43 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Appendix D:  Criteria for Identifying ECG Values that Reflect Potentially Clinically 
Significant Change 
Parameter 
Criterion 
QTcF/QTcB 
>470 msec (females), >450 msec (males) 
PR Interval 
>200 msec 
Heart Rate 
<48  
>96  


 
Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
Page 44 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
Appendix E:  Rules for Determining “Worst” Value 
“Worst” Clinical Laboratory Value 
Rule 
Parameters 
Highest value 
Hematology: eosinophils, basophils, monocytes, methemoglobin, 
reticulocytes 
Serum chemistry:  ALT, AST, ALK-P, creatinine, total bilirubin, 
BUN, uric acid, LDH, TSH, creatine kinase, GGT, triglycerides, 
cholesterol (total) 
Urinalysis:  all categorical results 
Lowest value 
Hematology: neutrophils, RBC count, HCT, hemoglobin, platelets 
Serum chemistry: albumin, creatinine clearance, total protein, 
oxygen saturation 
Farthest from 
normal range 
midpoint 
 
Hematology: WBC count, lymphocytes, MCV, MCH, MCHC 
Serum chemistry: glucose (random), Na, K, phosphate, TBG, T4, 
calcium, chloride, bicarbonate 
Urinalysis:  specific gravity, pH 
 
“Worst” Vital Sign and Weight Measurement 
Parameter 
Criterion for “Worst” Vital Sign 
Systolic blood pressure 
Value farthest from 125 mmHg 
Diastolic blood pressure 
Value farthest from 75 mmHg 
Pulse 
Value farthest from 75 beats per minute 
Respiratory Rate 
Highest 
Weight 
Greatest weight loss from baseline 
 
  
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
 
Page 45 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Appendix F:  Rules for Scoring the Disease Assessment Scales 
1. TPS 
Polyp Scoring System Used to Evaluate Polyp Size in Each Nostril by Nasal Endoscopy 
 
 
2. The Lund-Mackay scoring system  
The Lund-Mackay scoring system as presented in the table below will be used to measure the polyp size 
in each nostril by computed tomography at all sites except those in the United Kingdom and the 
Netherlands. 
 
Lund-Mackay Scoring System 
 
Possible Scores1 
Maxillary  
0-2 
Anterior ethmoid  
0-2 
Posterior ethmoid  
0-2 
Sphenoid  
0-2 
Frontal  
0-2 
Osteomeatal complex  
0 or 2 
Total 
 
1. Scale: 0 = absence; 1= partial opacification; 2= complete opacification. 
 
 
 
Polyp Score 
Polyp Size 
0 
No polyps 
1 
Small polyps in the middle meatus not reaching below the inferior border of the middle 
turbinate 
2 
Polyps reaching below the lower border of the middle turbinate 
3 
Large polyps reaching the lower border of the inferior turbinate or polyps medial to the 
middle turbinate 
4 
Large polyps causing complete obstruction of the inferior nasal cavity 
Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Omalizumab is effective in allergic and 
nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol 2013;131(1):110-6 e1. 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
 
Page 46 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
3. University of Pennsylvania Smell Identification Test™ 
The University of Pennsylvania Smell Identification Test consists of 4 booklets, each 
containing 10 odorants with 1 odorant per page. The stimuli are embedded in plastic 
microcapsules on brown strips at the bottom of each page. Above each odorant strip is a 
multiple-choice question with 4 alternative words to describe the odor as in the model 
of a test page below. The patient is asked to release the odorant by rubbing the brown-
strip with the tip of a pencil and to indicate which of 4 words best describes the odor. 
Thus, each subject receives a score out of 40 possible correct answers (Scadding G, 
Hellings P, Alobid I, Bachert C, Fokkens W, van Wijk RG, et al. Diagnostic tools in 
Rhinology EAACI position paper. Clin Transl Allergy 2011;1[1]:2). 
 
 
Fornazieri MA, Pinna Fde R, Bezerra TF, Antunes MB, Voegels RL. Applicability of the University of Pennsylvania 
Smell Identification Test (SIT) in Brazilians: pilot study. Braz J Otorhinolaryngol 2010;76(6):695-9. 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
 
Page 47 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
4. Sino-nasal Outcome Test-22 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
 
Page 48 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
5. Visual Analogue Scales for Symptoms of Rhinosinusitis and Clinical Symptoms 
Improvement Scale  
The VASs rank symptoms from 0 (not troublesome) to 10 (most troublesome) on 
10 cm-long scales as below. 
 
How troublesome are each of your following symptoms of rhinosinusitus? 
a) 
Anterior nasal discharge 
 
Not troublesome  
 
 
 
 
Most troublesome 
 
b) 
Posterior nasal discharge 
 
Not troublesome  
 
 
 
 
Most troublesome 
 
c) 
Nasal congestion, blockade, or obstruction 
 
Not troublesome  
 
 
 
 
Most troublesome 
 
d) 
Decreased sense of smell 
 
Not troublesome  
 
 
 
 
Most troublesome 
 
e) 
Facial pain or pressure 
 
Not troublesome  
 
 
 
 
Most troublesome 
 
The clinical symptoms improvement scale ranks symptom troublesomeness from 0 (not 
troublesome) to 10 (worst thinkable troublesome) on a 10 cm-long scale as below. 
How troublesome are your symptoms of rhinosinusitis? 
 
Not troublesome                                                                 Worst thinkable troublesome 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
 
Page 49 of 175 
CONFIDENTIAL 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
 
The symptomatology or symptom troublesomeness can be divided into “mild,” 
“moderate,” and “severe” categories based on total score: 
 
Mild=0 through 3 
 
Moderate= >3 through 7 
 
Severe= >7 through 10 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 50 of 175 
CONFIDENTIAL 
 
 
6. 36-Item Short Form Health Survey 
 
SF-36v2 Health Survey Single-Item Presentation Text Standard, United States (English) 
Note: Item SF36v2_BP1 (Item #21) has 6 answers, not 5 answers; see entry for item at end of sheet for more detail. 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
 
Your Health and Well-Being 
 
Score=1 
Score=2 
Score=3 
Score=4 
Score=5 
 
 
This survey asks for your views about your 
health.  This information will help keep track of 
how you feel and how well you are able to do 
your usual activities. Thank you for completing 
this survey! 
 
For each of the following questions, please 
select the one box that best describes your 
answer. 
 
 
 
 
 
SF36v2_GH1 
None 
In general, would you say your health is: 
Excellent 
Very good 
Good 
Fair 
Poor 
SF36v2_HT 
None 
Compared to one year ago, how would you 
rate your health in general now? 
Much 
better 
now than 
one year 
ago 
Somewhat 
better now 
than one 
year ago 
About the 
same as 
one year 
ago 
Somewhat 
worse 
now than 
one year 
ago 
Much 
worse 
now than 
one year 
ago 
SF36v2_PF01 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in vigorous 
activities, such as running, lifting heavy 
objects, participating in strenuous sports?  If 
so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF02 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in moderate 
activities, such as moving a table, pushing a 
vacuum cleaner, bowling, or playing golf?  If 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 51 of 175 
CONFIDENTIAL 
 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
so, how much? 
SF36v2_PF03 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in lifting or 
carrying groceries?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF04 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in climbing 
several flights of stairs?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF05 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in climbing one 
flight of stairs?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF06 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in bending, 
kneeling, or stooping?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF07 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in walking more 
than a mile?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF08 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in walking 
several hundred yards?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF09 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in walking one 
hundred yards?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_PF10 
The following question is about activities you 
might do during a typical day.  
Does your health now limit you in bathing or 
dressing yourself?  If so, how much? 
Yes, 
limited a 
lot 
Yes, 
limited a 
little 
No, not 
limited at 
all 
  
  
SF36v2_RP1 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities?  
Cut down on the amount of time you spent on 
work or other activities as a result of your 
physical health 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 52 of 175 
CONFIDENTIAL 
 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
SF36v2_RP2 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Accomplished less than you would like as a 
result of your physical health 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RP3 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities?  
Were limited in the kind of work or other 
activities as a result of your physical health 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RP4 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Had difficulty performing the work or other 
activities as a result of your physical health (for 
example, it took extra effort) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RE1 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Cut down on the amount of time you spent on 
work or other activities as a result of any 
emotional problems (such as feeling 
depressed or anxious) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RE2 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities?  
Accomplished less than you would like as a 
result of any emotional problems (such as 
feeling depressed or anxious) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_RE3 
During the past 4 weeks, how much of the 
time have you had any of the following 
problems with your work or other regular 
daily activities? 
Did work or other activities less carefully than 
usual as a result of any emotional problems 
(such as feeling depressed or anxious) 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_SF1 
None 
During the past 4 weeks, to what extent has 
your physical health or emotional problems 
interfered with your normal social activities with 
family, friends, neighbors, or groups? 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
SF36v2_BP1 
None 
How much bodily pain have you had during the 
past 4 weeks? 
See end of document for answers #1-#6 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 53 of 175 
CONFIDENTIAL 
 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
SF36v2_BP2 
None 
During the past 4 weeks, how much did pain 
interfere with your normal work (including both 
work outside the home and housework)? 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
SF36v2_VT1 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you feel full of life? 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH1 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you been very nervous?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH2 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you felt so down in the dumps that 
nothing could cheer you up?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH3 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you felt calm and peaceful?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_VT2 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you have a lot of energy?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH4 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
How much of the time during the past 4 weeks 
have you felt downhearted and depressed?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 54 of 175 
CONFIDENTIAL 
 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
feeling.   
SF36v2_VT3 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you feel worn out?   
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_MH5 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
have you been happy?  
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_VT4 
This question is about how you feel and how 
things have been with you during the past 4 
weeks.  Please give the one answer that 
comes closest to the way you have been 
feeling.   
How much of the time during the past 4 weeks 
did you feel tired?  
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
SF36v2_SF2 
None 
During the past 4 weeks, how much of the time 
has your physical health or emotional 
problems interfered with your social activities 
(like visiting with friends, relatives, etc.)? 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
 SF36v2_GH2 
How TRUE or FALSE is the following 
statement for you? 
I seem to get sick a little easier than other 
people. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 
SF36v2_GH3 
How TRUE or FALSE is the following 
statement for you? 
I am as healthy as anybody I know. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 
SF36v2_GH4 
How TRUE or FALSE is the following 
statement for you? 
I expect my health to get worse. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 
SF36v2_GH5 
How TRUE or FALSE is the following 
statement for you? 
My health is excellent. 
Definitely 
true 
Mostly 
true 
Don't know 
Mostly 
false 
Definitely 
false 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 55 of 175 
CONFIDENTIAL 
 
 
 
Data for item SF36v2_BP1 (item #21 in the survey template) 
 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
Answer 
Text 6 
SF36v2_BP1 
None 
How much bodily pain have you had during the 
past 4 weeks? 
None 
Very mild 
Mild 
Moderate 
Severe 
Very severe 
SF-36v2® Health Survey Ó 1992, 1996, 2000, 2010 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Single-Item Presentation Text Standard, United States (English)) 
 
 
 
 
 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 56 of 175 
CONFIDENTIAL 
 
 
7. Asthma Control Test™ 
Asthma Control Test™ Single-Item Presentation Text, United States (English) 
Item Name 
Instructions 
Question Text 
Answer 
Text 1 
Answer 
Text 2 
Answer 
Text 3 
Answer 
Text 4 
Answer 
Text 5 
 
Asthma Control Test™ 
 
 
 
 
 
 
 
This survey was designed to help you 
describe your asthma and how your asthma 
affects how you feel and what you are able 
to do.  For each of the following questions, 
please select the one box that best 
describes your answer. 
 
 
 
 
 
 
ACT1 
None 
In the past 4 weeks, how much of the time did your 
asthma keep you from getting as much done at 
work, school or at home? 
All of the 
time 
Most of the 
time 
Some of 
the time 
A little of 
the time 
None of 
the time 
ACT2 
None 
During the past 4 weeks, how often have you had 
shortness of breath? 
More than  
once a 
day 
Once a 
day 
3 to 6 
times a 
week 
Once or 
twice 
a week 
Not at all 
ACT3 
None 
During the past 4 weeks, how often did your 
asthma symptoms (wheezing, coughing, shortness 
of breath, chest tightness or pain) wake you up at 
night or earlier than usual in the morning? 
4 or more 
nights a 
week 
2 to 3 
nights a 
week 
Once a 
week 
Once or 
Twice 
Not at all 
ACT4 
None 
During the past 4 weeks, how often have you used 
your rescue inhaler or nebulizer medication (such 
as Albuterol, Ventolin®, Proventil®, or Maxair®)? 
3 or more 
times per 
day 
1 or 2 
times per 
day 
2 or 3 
times per 
week 
Once a 
week 
or less 
Not at all 
ACT5 
None 
How would you rate your asthma control during the 
past 4 weeks? 
Not 
Controlled 
at all 
Poorly 
Controlled 
Somewhat  
Controlled 
Well 
Controlled 
Completely 
Controlled 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 57 of 175 
CONFIDENTIAL 
 
 
Asthma Control Test™ © QualityMetric Incorporated 2002, 2004, 2011. All rights reserved. 
Asthma Control Test™ is a trademark of QualityMetric Incorporated. 
Single-Item Presentation Text, United States (English) 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 58 of 175 
CONFIDENTIAL 
 
 
Appendix G:  List of Review Files Provided by Allakos to InClin  
 
1. Protocol deviations – identified by subject and a flag per each deviation type. 
2. Coding or coding advice on any concomitant medication or adverse event that requires special review and input from Allakos or per the DMC. 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 59 of 175 
CONFIDENTIAL 
 
 
 
Appendix H:  List of Tables, Figures, and Listings 
List of Tables 
 
Table 
Number 
 
Table Description 
14.1.1.1 
Subject Disposition (All Subjects) 
14.1.1.2 
Subject Disposition by Region (All Subjects) 
14.1.2.1 
Early Discontinuation of Study Drug by Time Period (Safety Population) 
14.1.2.2 
Early Discontinuation of Study Drug by Time Period (MITT Population) 
14.1.3 
Protocol Deviations (MITT Population) 
14.1.4.1 
Demographic and Baseline Characteristics (Safety Population) 
14.1.4.2 
Demographic and Baseline Characteristics (MITT Population) 
14.1.4.3 
Demographic and Baseline Characteristics by Region (MITT Population) 
14.1.5 
Medical History at Baseline (Safety Population) 
14.1.6 
Baseline Physical and Neurological Examination (Safety Population) 
14.1.7.1 
Prior Medications (Safety Population) 
14.1.7.2.1 
Concomitant Medications (Safety Population) 
14.1.7.2.2 
Concomitant Medications (MITT Population) 
14.1.7.3 
Study Drug Administration (Safety Population) 
14.2.8.1 
Change in Total Polyp Score (TPS) from Baseline to Week 12 (No 
Imputation) (MITT Population) 
14.2.8.2 
Change in Total Polyp Score (TPS) from Baseline to Week 12 (With 
Imputation ) (MITT Population) 
14.2.8.3 
Change in Total Polyp Score (TPS) from Baseline to Week 12 (No 
Imputation) (ITT Population) 
14.2.8.4 
Change in Total Polyp Score (TPS) from Baseline to Week 12 (No 
Imputation) (PP Population) 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 60 of 175 
CONFIDENTIAL 
 
 
Table 
Number 
 
Table Description 
14.2.9.1 
Change in Total Polyp Score (TPS) from Baseline over Time (No 
Imputation) (MITT Population) 
14.2.9.2 
Change in Total Polyp Score (TPS) from Baseline over Time (With 
Imputation) (MITT Population) 
14.2.9.3 
Change in Total Polyp Score (TPS) from Baseline over Time (No 
Imputation) (ITT Population) 
14.2.9.4 
Change in Total Polyp Score (TPS) from Baseline over Time (No 
Imputation) (PP Population) 
14.2.9.5 
Change in Total Polyp Score (TPS) from Baseline over Time (Without 
Time Interaction) (MITT Population) 
14.2.9.6 
Percent Change in Total Polyp Score (TPS) from Baseline over Time 
(Without Time Interaction) (MITT Population) 
14.2.9.7 
Absolute Measurements in Total Polyp Score (TPS) from Baseline over 
Time (Without Time Interaction) (MITT Population) 
14.2.9.8 
Total Polyp Score (TPS) – Time to Response at Any Time (MITT 
Population) 
14.2.10.1 
Subgroup Analysis of TPS Score at Week 12 by Gender (MITT 
Population) 
14.2.10.2 
Subgroup Analysis of TPS Score at Week 12 by Age (MITT Population) 
14.2.10.3 
Subgroup Analysis of TPS Score at Week 12 by Asthma (MITT 
Population) 
14.2.10.4 
Subgroup Analysis of TPS Score at Week 12 by 1-point Reduction 
Responder Criteria (MITT Population) 
14.2.10.5 
Subgroup Analysis of TPS Score at Week 12 by 20% Reduction 
Responder Criteria (MITT Population) 
14.2.10.6 
Subgroup Analysis of TPS Score at Week 12 by 30% Reduction 
Responder Criteria (MITT Population) 
14.2.11 
Change in Size of Polyps (Lund-Mackay Score) from Baseline to Week 
12 (MITT Population) 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 61 of 175 
CONFIDENTIAL 
 
 
Table 
Number 
 
Table Description 
14.2.12.1 
Change in Peak Nasal Inspiration Flow (PNIF) from Baseline over Time 
(MITT Population) 
14.2.12.2 
Peak Nasal Inspirational Flow (PNIF) – Time to Response at Any Time 
(MITT Population) 
14.2.13.1 
Change in Sense of Smell (UPSIT Total Score) from Baseline over Time 
(MITT Population) 
14.2.13.2 
Sense of Smell (UPSIT) – Time to Response at Any Time (MITT 
Population) 
14.2.14.1 
Sino-nasal Outcome Test-22 (SNOT-22) (Five Most Important Items) at 
Week 12 (MITT Population) 
14.2.14.2 
Change in SNOT-22 (Total Score of Five Most Important Items) from 
Baseline over Time (MITT Population) 
14.2.14.3 
Change in SNOT-22 (Total Score of All Items) from Baseline over Time 
(MITT Population) 
14.2.14.4 
Sino-nasal Outcome Test-22 (SNOT-22) – Time to Response at Any 
Time (MITT Population) 
14.2.15.1 
Visual Analogue Scale (VAS) by Symptom (MITT Population) 
14.2.15.2 
Change in Visual Analogue Scale (VAS by Symptom) from Baseline over 
Time (MITT Population) 
14.2.15.3 
Change in Visual Analogue Scale (VAS Total Score) from Baseline over 
Time (MITT Population) 
14.2.15.4 
Visual Analogue Scale (VAS) – Time to Response at Any Time (MITT 
Population) 
14.2.15.5 
Change in Clinical Symptoms Improvement Scale (Total Score) from 
Baseline over Time (MITT Population) 
14.2.16 
Change in 36-Item Short Form Health Survey (SF-36 Total Score) from 
Baseline over Time (MITT Population) 
14.2.17.1 
Biomarker Analysis: Change in Biomarkers from Baseline Over Time 
(Biomarker Population, Sub-Study) 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 62 of 175 
CONFIDENTIAL 
 
 
Table 
Number 
 
Table Description 
14.2.17.2 
Biomarker Analysis: Percent Change in Biomarkers from Baseline over 
Time (Biomarker Population, Sub-Study) 
14.2.17.3 
Biomarker Analysis: Change in Biomarkers from Baseline over Time 
(Biomarker Population, All Patients) 
14.2.17.4 
Biomarker Analysis: Percent Change in Biomarkers from Baseline over 
Time (Biomarker Population, All Patients) 
14.2.18.1 
Change in Forced Expiratory Volume in 1 Second (FEV1) from Baseline 
to Week 7 (MITT Population in Patients with Comorbid Asthma) 
14.2.18.2 
Change in Forced Vital Capacity (FVC) from Baseline to Week 7 (MITT 
Population in Patients with Comorbid Asthma) 
14.2.18.3 
Change in Forced Expiratory Flow (FEF) from Baseline to Week 7 
(MITT Population in Patients with Comorbid Asthma) 
14.2.18.4 
Change in Asthma Control Test (ACT) from Baseline to Week 12 (MITT 
Population in Patients with Comorbid Asthma) 
14.2.18.5.1 
Use of Asthma Rescue Therapy from Baseline to Week 12 (MITT 
Population in Patients with Comorbid Asthma) 
14.2.18.5.2 
Use of Asthma Rescue Therapy - Shift from Baseline to Week 12 (MITT 
Population in Patients with Comorbid Asthma) 
14.3.1.19.1 
Overall Summary of All Adverse Events (Safety Population) 
14.3.1.19.2.
1 
Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term (Safety Population) 
14.3.1.19.2.
2 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term and Severity (Safety Population) 
14.3.1.19.2.
3 
Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term and Relationship to Study Drug (Safety Population) 
14.3.2.19.3 
Treatment-Emergent Serious Adverse Events by System Organ Class and 
Preferred Term (Safety Population) 
14.3.2.19.4.
1 
Treatment-Emergent Fatal Serious Adverse Events by System Organ 
Class and Preferred Term (Safety Population) 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 63 of 175 
CONFIDENTIAL 
 
 
Table 
Number 
 
Table Description 
14.3.2.19.4.
2 
Treatment-Emergent Non-Fatal Serious Adverse Events by System Organ 
Class and Preferred Term (Safety Population) 
14.3.1.19.5 
Treatment-Emergent Severe Adverse Events by System Organ Class and 
Preferred Term (Safety Population) 
14.3.1.19.6 
Day 0 Treatment Emergent Adverse Events by System Organ Class and 
Preferred Term (Safety Population) 
14.3.1.19.7 
Post-Treatment Adverse Events by System Organ Class and Preferred 
Term (Safety Population) 
14.3.1.19.8.
1 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety 
Population Subgroup: Asthma Present) 
14.3.1.19.8.
2 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety 
Population Subgroup: Asthma Absent) 
14.3.1.19.8.
3 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety 
Population Subgroup: Using Concomitant Medication at Any Time 
During the Study) 
14.3.1.19.8.
4 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety 
Population Subgroup: Not Using Concomitant Medication at Any Time 
During the Study) 
14.3.1.19.8.
5 
Treatment-Emergent Adverse Events by SOC and Preferred Term in at 
least 5 Subjects in any of Treatment Group (Safety Population) 
14.3.4.20.1.
1 
Hematology Values and Changes from Baseline at All Visits – 
Conventional Units (Safety Population) 
14.3.4.20.1.
2 
Hematology Values and Changes from Baseline at All Visits – SI Units 
(Safety Population) 
14.3.4.20.1.
3 
Hematology – Shift from Baseline (Safety Population) 
14.3.4.20.2.
1 
Serum Chemistry Values and Changes from Baseline at All Visits – 
Conventional Units (Safety Population) 
14.3.4.20.2.
2 
Serum Chemistry Values and Changes from Baseline at All Visits – SI 
Units (Safety Population) 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 64 of 175 
CONFIDENTIAL 
 
 
Table 
Number 
 
Table Description 
14.3.4.20.2.
3 
Serum Chemistry – Shift from Baseline (Safety Population) 
14.3.4.20.3.
1 
Urinalysis Values at All Visits – (Safety Population) 
14.3.4.20.3.
2.1 
Urinalysis – Shift from Baseline (Part 1 of  2) (Safety Population)  
14.3.4.20.3.
2.2 
Urinalysis – Shift from Baseline (Part 2 of  2) (Safety Population) 
14.3.4.21.1 
Vital Signs – Day 0 Pre-Dose and Post-Dose (Safety Population) 
14.3.4.21.2 
Vital Signs – Screening and Post Day 0 (Safety Population) 
14.3.4.21.3 
Incidence of Potentially Clinically Significant Vital Sign Results (Safety 
Population) 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 65 of 175 
CONFIDENTIAL 
 
 
List of Figures 
Figure 
Number 
 
Figure Description 
14.2.1.1  
Least Squares Mean Change in Total Polyp Score (TPS) (MITT 
Population) 
14.2.1.2 
Least Squares Mean Change in Total Polyp Score (TPS) (MITT 
Population in Patients with Comorbid Asthma) 
14.2.1.3 
Kaplan-Meier Curves for Time to 1-point Reduction in Total Polyp Score 
(TPS) (MITT Population) 
14.2.2 
Least Squares Mean Change in Peak Nasal Inspiratory Flow (PNIF) 
(MITT Population) 
14.2.3 
Least Squares Mean Change in University of Pennsylvania Smell 
Identification Test (UPSIT) (MITT Population) 
14.2.4 
Least Squares Mean Change in 22-item Sinonasal Outcome Test (SNOT-
22) (MITT Population) 
14.2.5 
Least Squares Mean Change in Visual Analogue Scale (VAS) (MITT 
Population) 
14.2.6 
Least Squares Mean Change in Forced Expiratory Volume in 1 Second 
(FEV1) (MITT Population in Patients with Comorbid Asthma) 
14.2.7 
Least Squares Mean Change in Asthma Control Test (ACT) (MITT 
Population in Patients with Comorbid Asthma) 
14.2.8 
Least Squares Mean Change in Blood Eosinophil Count (Biomarker 
Population) 
 
 
 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 66 of 175 
CONFIDENTIAL 
 
 
List of Data Listings 
 
Listing 
Number 
 
Listing Description 
16.2.1.1.1 
Subject Populations 
16.2.1.1.2 
Subject Disposition 
16.2.1.1.3 
Subject Visit Dates 
16.2.2.2 
Protocol Deviations  
16.2.2.3 
Inclusion/Exclusion Findings 
16.2.1.4.1 
Informed Consent 
16.2.1.4.2 
Withdrawal of Consent 
16.2.4.5.1 
Demographics and Baseline Characteristics (Part 1 of 2) 
16.2.4.5.2 
Demographics and Baseline Characteristics (Part 2 of 2) 
16.2.4.6 
Relevant Respiratory History at Screening 
16.2.4.7 
Medical History at Screening 
16.2.4.8 
Physical and Neurological Examination 
16.2.4.9 
Symptom Directed Physical Examination 
16.2.4.10 
Electrocardiogram at Screening 
16.2.4.11.1 
Pregnancy Test 
16.2.4.11.2 
Pregnancy Report during Study 
16.2.4.12 
Follicle-Stimulating Hormone (FSH) Test at Screening 
16.2.4.13 
Fecal Sample Test at Screening 
16.2.4.14 
Anti-Drug Antibody (ADA) 
16.2.4.15 
Exploratory Biomarkers 
16.2.4.16 
Serum Samples for Total Immunoglobulin E and ImmunoCAP on Day -3 
 
 
16.2.4.17 
Prior Medications 
16.2.4.18 
Concomitant Medications 
16.2.4.19 
Intranasal Steroid Adjustment at Day 0 
16.2.5.20 
Study Drug Administration 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 67 of 175 
CONFIDENTIAL 
 
 
Listing 
Number 
 
Listing Description 
16.2.6.21.1 
Total Polyp Score (TPS) 
16.2.6.21.2 
Size of Polyps (Lund-Mackay Score) 
16.2.6.21.3 
Peak Nasal Inspiratory Flow (PNIF) 
16.2.6.21.4 
University of Pennsylvania Smell Identification Test (UPSIT) 
16.2.6.21.5 
Sino-nasal Outcome Test-22 (SNOT-22) 
16.2.6.21.6 
Visual Analogue Scale (VAS) 
16.2.6.21.7 
Clinical Symptoms Improvement Scale 
16.2.6.21.8.1 
36-Item Short Form Health Survey (SF-36) (Part 1 of 3) 
16.2.6.21.8.2 
36-Item Short Form Health Survey (SF-36) (Part 2 of 3) 
16.2.6.21.8.3 
36-Item Short Form Health Survey (SF-36) (Part 3 of 3) 
16.2.6.21.9 
Asthma Control Test (ACT) 
16.2.6.21.10 
Spirometry Test 
16.2.6.21.11.1 Sub-study Biomarkers (Part 1 of 2) 
16.2.6.21.11.2 Sub-study Biomarkers (Part 2 of 2) 
16.2.7.22.1 
Adverse Events 
16.2.7.22.2 
Treatment-Emergent Serious Adverse Events (Collected on AE CRF) 
16.2.7.22.3 
Fatal Treatment-Emergent Serious Adverse Events (Collected on AE 
CRF) 
16.2.7.22.4 
Non-Fatal Treatment-Emergent Serious Adverse Events (Collected on AE 
CRF) 
16.2.8.23.1.1 
Central Laboratory Normal Ranges – Conventional Units 
16.2.8.23.1.2 
Central Laboratory Normal Ranges – SI Units 
16.2.8.23.2.1 
Hematology – Conventional Units (Part 1 of 2) 
16.2.8.23.2.2 
Hematology – Conventional Units (Part 2 of 2) 
16.2.8.23.2.3 
Hematology – SI Units 
16.2.8.23.3.1 
Serum Chemistry – Conventional Units (Part 1 of 2) 
16.2.8.23.3.2 
Serum Chemistry – Conventional Units (Part 2 of 2) 
16.2.8.23.3.3 
Serum Chemistry – SI Units 
16.2.8.23.4 
Urinalysis 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 68 of 175 
CONFIDENTIAL 
 
 
Listing 
Number 
 
Listing Description 
16.2.8.24.1 
Vital Signs 
16.2.8.24.2 
Vital Sign Results of Potential Clinical Significance 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 69 of 175 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix I:  Table Layouts 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 70 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.1.1 
Subject Disposition 
All Subjects 
 
Placebo 
AK001 
25 mg 
AK001 
250 mg 
AK001 
Combined 
Total 
 
 
 
 
 
Subjects Screened 
 
 
 
 
n 
 
 
 
 
 
Subjects Randomized [1] 
n 
n 
n 
n 
n 
 
 
 
 
 
Safety Population [2] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
ITT Population [3] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
MITT Population  [4] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
PP Population [5] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Completed Study 
 
 
 
 
 
Yes 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Completed study and completed treatment 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Completed study but off treatment 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
No 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
All Reasons for Study Drug Discontinuation  
 
 
 
 
 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
All Reasons for Study Discontinuation [6] 
 
 
 
 
 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Primary Reason for Study Discontinuation 
 
 
 
 
 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
. . . 
 
 
 
 
 
 
 
 
 
 
[1] All percentages are based on the number of subjects randomized. 
[2]All randomized subjects who take at least one dose of study drug. 
[3]All randomized subjects. 
[4]All randomized subjects who take at least one dose of the study drug and have both a baseline and at least one post-baseline effifcay assessment. 
[5]All MITT population subjects who have a week 12 visit and valid efficacy measurements. 
[6]Subjects may be counted for more than one reason for study discontinuation but are counted only once for primary reason for discontinuation. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 71 of 175 
CONFIDENTIAL 
 
 
Note: The following 5 subjects vvv, www, xxx, yyy, zzz were randomized but not dosed. (programming note: List the subject IDs) 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 72 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.1.2 
Subject Disposition by Region 
All Subjects 
 
Region 
Placebo 
AK001 
25 mg 
AK001 
250 mg 
AK001 
Combined 
Total 
 
 
 
 
 
United States 
Subjects Screened 
 
 
 
 
n 
 
 
 
 
 
 
 
Subjects Randomized [1] 
n 
n 
n 
n 
n 
 
 
 
 
 
Safety Population [2] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
ITT Population [3] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
MITT Population  [4] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
PP Population [5] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Completed Study 
 
 
 
 
 
 
Yes 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Completed study and completed treatment 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Completed study but off treatment 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
No 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
All Reasons for Study Drug Discontinuation  
 
 
 
 
 
 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
All Reason for Study Discontinuation [6] 
 
 
 
 
 
 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Primary Reason for Study Discontinuation 
 
 
 
 
 
 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
. . . 
 
 
 
 
 
 
 
 
 
 
European Union 
 
 
 
 
 
  . . . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 73 of 175 
CONFIDENTIAL 
 
 
 
[1] Percentages for screen failures are based on the number of subjects screened – subjects may be counted in multiple screen failure categories.  All other percentages are based on 
the number of subjects randomized. 
[2]All randomized subjects who take at least one dose of study drug. 
[3]All randomized subjects. 
[4]All randomized subjects who take at least one dose of the study drug and have both a baseline and at least one post-baseline effifcay assessment. 
[5]All MITT population subjects who have a week 12 visit and valid efficacy measurements. 
 [6]Subjects may be counted for more than one reason for study discontinuation but are counted only once for primary reason for discontinuation. 
Note: The following 5 subjects vvv, www, xxx, yyy, zzz were randomized but not dosed. (programming note: List the subject IDs) 
 
path\t_program.sas date 
time   
 
Programming note: Start each region on a new page. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 74 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.2.1 
Early Discontinuation of Study Drug by Time Period 
Safety Population 
 
Placebo 
AK001 
25 mg 
AK001 
250 mg 
AK001 
Combined 
Total 
 
 
 
 
 
Subjects Taking at Least One Dose 
n 
n 
n 
n 
n 
 
 
 
 
 
Early Discontinuation of Study Drug [1] 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Early Discontinuation of Study Drug before 
Day 14 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
. . . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Early Discontinuation of Study Drug During 
Days >14-21 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reason 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Reason 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
. . . 
 
 
 
 
 
 
 
 
 
 
Early Discontinuation of Study Drug During 
Days >21-49 
n (%) 
            n (%) 
n (%) 
              n (%) 
n (%) 
Reason 1 
n (%) 
            n (%) 
n (%)     
              n (%) 
n (%) 
Reason 2 
. . . 
n (%) 
            n (%) 
n (%)     
 
 
 
              n (%) 
 
 
 
n (%) 
 
 
 
 
 
 
Note: Percentages are based on the number of subjects in the Safety Population. 
[1] Drug discontinuation prior to Week 12 will be considered early.  
 
path\t_program.sas date 
time   
 
Programming note: Repeat this table for MITT population (Table 14.1.2.2) 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 75 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.3 
Protocol Deviations  
MITT Population 
 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
Total 
(N=   ) 
 
 
 
 
 
  All Deviations  
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Informed consent  
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Randomization error 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Safety 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Efficacy 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         IP/Treatment deviation 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Other deviations 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Type of Protocol Deviation [1] 
 
 
 
 
 
         Informed consent procedures 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Eligibility criteria 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Study procedure not done 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Study procedure not per protocol 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Patient not withdrawn as per protocol 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Study drug administration 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Missed study visit 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Visit out of study window 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Safety reporting 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Prohibited con meds/therapies 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Laboratory samples 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Study drug storage and handling  
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
         Other deviations 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
[1] All categories include that fall under the “other” category 
 
path\t_program.sas date time   
 
Programming note: The categories in first column should come from SAP section 7.2 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 76 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.4.1 
Demographic and Baseline Characteristics 
Safety Population 
 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
Total 
(N=   ) 
 
 
 
 
 
Age at Informed Consent (years) 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx, xx 
 
 
 
 
 
   < Median 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   ≥ Median 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Gender 
 
 
 
 
 
Male 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Female 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
Hispanic or Latino 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Not Hispanic or Latino 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Race 
 
 
 
 
 
American Indian or Alaska Native 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Asian  
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Black or African American 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Native Hawaiian or Other Pacific Islander 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
White 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Other 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
Geographic Region  
 
 
 
 
 
United States  
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
European Union 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
path\t_program.sas date 
time   
Table continues on next page. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 77 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 2 of x 
AK001-002 
Table 14.1.4.1 
Demographic and Baseline Characteristics 
Safety Population (cont’d) 
 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
Total 
(N=   ) 
 
 
 
 
 
Subject Consented 
 
 
 
 
 
  Yes 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
  No 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Height (cm) 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx, xx 
 
 
 
 
 
Weight (kg) 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx, xx 
 
 
 
 
 
 
BMI (kg/m2) 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx, xx 
 
 
 
 
 
 
path\t_program.sas date 
time   
 
Programming note: Repeat table for MITT Population (Table 14.1.4.2). 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 78 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 3 of x 
AK001-002 
Table 14.1.4.3 
Demographic and Baseline Characteristics by Region 
MITT Population 
 
Region 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
Total 
(N=   ) 
 
 
 
 
 
United States 
Age at Informed Consent (years) 
 
 
 
 
 
 
n 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
   < Median 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   ≥ Median 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Gender 
 
 
 
 
 
 
Male 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Female 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
 
Hispanic or Latino 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Not Hispanic or Latino 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
. . . 
 
 
 
 
 
 
 
 
 
 
 
 
European Union 
 
 
 
 
 
 
. . . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
path\t_program.sas date 
time   
 
Programming note: See previous mock table for variables to include.   Exclude Geographic Region. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 79 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.5 
Medical History at Baseline 
Safety Population 
 
 
MedDRA System Organ Class 
Placebo 
(N= ) 
AK001 
25 mg 
(N= ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
Total 
(N=   ) 
 
 
 
 
 
Blood and Lymphatic System Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Cardiac Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Congenital, Familial and Genetic Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Ear and Labyrinth Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Endocrine Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Eye Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Gastrointestinal Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
General Disorders and Administration Site 
Conditions 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Hepatobiliary Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Immune System Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Infections and Infestations 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Injury, Poisoning and Procedural 
Complications 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Investigations 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Metabolism and Nutrition Disorders 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
etc. 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
path\t_program.sas date 
time   
 
Programming note: Sort table based on SOC order alphabetically 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 80 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.6 
Baseline Physical and Neurological Examination 
Safety Population 
 
Body System 
Findings 
Placebo 
(N=   ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
 
Total 
(N=  ) 
 
 
 
 
 
Skin 
 
 
 
 
 
 
Normal 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
Abnormal NCS 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Abnormal CS 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Head 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
Note: NCS = Not clinically significant, CS = Clinically significant. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include all physical examination body systems in SAP section 7.5: Skin, Head, Eyes, Ears, Nose, Throat, Thyroid, Lungs, Cardiovascular system, 
Abdomen, Extremities, Lymph nodes and neurological examination. 
  


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 81 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.7.1 
Prior Medications 
Safety Population 
 
ATC Class (Level 1) /  
   ATC Class (Level 3)/ 
       Generic Drug Name 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
Total 
(N=   ) 
 
 
 
 
 
Subjects Receiving Prior [1] Medications 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
ATC Class (Level 1) 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
ATC Class (Level 3) 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
  ATC Class (Level 3) 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
  Generic Drug Name 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
  Generic Drug Name 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
… 
 
 
 
 
 
ATC Class (Level 1) 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
ATC Class (Level 3) 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Prior medications are those that started within the 30 days before Screening. 
Note: At each level of summation (overall, ATC classes, generic drug name), subjetcs reporting more than once of the same medication are counted only once for a particular 
medication class and medication. Each summary is ordered alphabetically by ATC class and generic drug name within each ATC class. 
 
path\t_program.sas date 
time   
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 82 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.7.2.1 
Concomitant Medications 
Safety Population 
 
ATC Class (Level 1) /  
   ATC Class (Level 3)/ 
       Generic Drug Name 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
Total 
(N=   ) 
 
 
 
 
 
Subjects Receiving Concomitant[1] Medications 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
ATC Class (Level 1) 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
ATC Class (Level 3) 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
  ATC Class (Level 3) 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
  Generic Drug Name 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
  Generic Drug Name 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
ATC Class (Level 1) 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
ATC Class (Level 3) 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 1 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
   Generic Drug Name 2 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Concomitant medications are those medications taken at the start of study drug or initiated after the initial dose of study drug. 
Note: At each level of summation (overall, ATC classes, generic drug name), subjects reporting more than once of the same medication are counted only once for a particular 
medication class and medication. Each summary is ordered alphabetically by ATC class and generic drug name within each ATC class. 
 
path\t_program.sas date 
time   
 
Programming note: Repeat table for MITT Population (Table 14.1.7.2.2). 
Programming note: Separate prior meds and concomitant meds (2 tables) 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 83 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.1.7.3 
Study Drug Administration 
Safety Population 
 
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
 
 
 
 
Day 0  
Arm for Infusion 
 
 
 
 
 
Left Arm 
Right Arm 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
Full Infusion Given 
 
 
 
 
 
Yes 
n (%) 
n (%) 
n (%) 
n (%) 
 
No 
n (%) 
n (%) 
n (%) 
n (%) 
 
If Yes, Total Volume of Study Drug 
Administered (mL) 
    n 
 
 
n 
 
 
n 
 
 
n 
 
 
n 
 
    Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
    Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
    Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
If No, Total Amount Given (mL) 
 
 
 
 
       n 
n 
n 
n 
n 
       Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
       Median 
xx.x 
xx.x 
xx.x 
xx.x 
       Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Infusion Interrupted 
 
 
 
 
 
Yes 
n (%) 
n (%) 
n (%) 
n (%) 
 
No 
n (%) 
n (%) 
n (%) 
n (%) 
 
If Yes, Number of Times Interrupted 
 
 
 
 
 
    1 
n (%) 
n (%) 
n (%) 
n (%) 
 
       2 
n (%) 
n (%) 
n (%) 
n (%) 
 
    >=3 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
Day 21 
Arm for Infusion 
 
 
 
 
 
  … 
n (%) 
n (%) 
n (%) 
n (%) 
 
   
 
 
 
 
 
Full Infusion Given 
 
 
 
 
 
   … 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 84 of 175 
CONFIDENTIAL 
 
 
 
Infusion Interrupted 
 
 
 
 
 
   … 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 49  
Arm for Infusion 
 
 
 
 
 
   … 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
Full Infusion Given 
 
 
 
 
 
  … 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
Infusion Interrupted 
 
 
 
 
 
  … 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
Total Exposure (mL) 
 
 
 
 
 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety Population. n = Number of subjects in the specific category. Percentages are calculated as 100 x (n/N).  
 
path\t_program.sas date 
time   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 85 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.8.1 
Change in Total Polyp Score (TPS) from Baseline to Week 12 
No Imputation 
MITT Population 
 
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined [4] 
(N= ) 
 
 
 
 
Baseline [1] 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Week 12 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Change from Baseline to Week 12 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
LS Mean  
xx.x [2] 
xx.x [2] 
xx.x [2] 
xx.x [4] 
   95% CI  
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [4] 
 
 
 
 
   LS Mean Difference (AK001 vs. Placebo)  
 
xx.x [3] 
xx.x [3] 
xx.x [4] 
    95% CI  
 
(xx, xx) [3] 
(xx, xx) [3] 
(xx, xx) [4] 
   p-value  
 
0.xxxx [3] 
0.xxxx [3] 
0.xxxx [4] 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 86 of 175 
CONFIDENTIAL 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment and asthma status (stratification factor). Baseline TPS score was included as a covariate. An unstructured covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
No imputations are made for missing data. 
 
path\t_program.sas date 
time   
 
Programming note:Repeat table 14.2.8.2 for Imputation method: Missing values are imputed by the average value of the placebo group at each specific time point.   
Repeat table 14.2.8.3 for no imputation and ITT population 
Repeat table 14.2.8.4 for no imputation and PP population                                 
 t 
                                
 
 
Overall 3-group ANOVA 
Effect  
 
DF [2] 
SE [2] 
Statistics [2]         p-value [2]     
Treatment 
 nn 
xx.xx         xx.xx                 0.xxxx 
Baseline TPS 
 nn 
xx.xx   
  xx.xx 
            0.xxxx 
Asthma  
 nn 
xx.xx 
  xx.xx                 0.xxxx 
 
 
 
Combined Treatment 2-group ANOVA 
 
DF [4] 
SE [4] 
Statistics [4]         p-value [4]     
nn 
xx.xx         xx.xx                 0.xxxx 
nn 
xx.xx   
  xx.xx 
            0.xxxx 
nn 
xx.xx 
  xx.xx                 0.xxxx 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 87 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.9.1 
Change in Total Polyp Score (TPS) from Baseline over Time 
No Imputation 
MITT Population 
 
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined [4] 
(N= )  
 
 
 
 
Baseline [1] 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Week 3 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Change from Baseline to Week 3 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
LS Mean  
xx.x [2] 
xx.x [2] 
xx.x [2] 
xx.x [4] 
   95% CI  
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [4] 
 
 
 
 
   LS Mean Difference (AK001 vs. Placebo) 
 
xx.x [3] 
xx.x [3] 
xx.x [4] 
    95% CI  
 
(xx, xx) [3] 
(xx, xx) [3] 
(xx, xx) [4] 
   p-value  
 
0.xxxx [3] 
0.xxxx [3] 
0.xxxx [4] 
… 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 88 of 175 
CONFIDENTIAL 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction, and asthma status (stratification factor). Baseline TPS was included as a covariate. An unstructured covariance 
model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
No imputations are made for missing data. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include the following raw score visits:  Baseline, Week 3, Week 7, and Week 16; and change from baseline for Week 3, Week 7, and Week 16.  
Repeat the following tables --- 
                 Table 14.2.9.2 Change in Total Polyp Score (TPS) from Baseline over Time (With Imputation) (MITT Population)  
                                 Programming note: Please adda  footnote for imputation method. 
                Table 14.2.9.3 Change in Total Polyp Score (TPS) from Baseline over Time (No Imputation) (ITT Population) 
                Table 14.2.9.4 Change in Total Polyp Score (TPS) from Baseline over Time (No Imputation) (PP Population) 
Table 14.2.9.5 Change in Total Polyp Score (TPS) from Baseline over Time (No Imputation, No Interaction) (MITT Population) 
Table 14.2.9.6 Percent Change in Total Polyp Score (TPS) from Baseline over Time (No Imputation, No Interaction) (MITT population) 
Table 14.2.9.7 Absolute Measurements in Total Polyp Score (TPS) from Baseline over Time (No Imputation, No Interaction) (MITT population) 
 Programming note: Time factor will include baseline as a level but baseline will not be included as a covariate in the model (needs to be a footnote as well). 
                
  
 
 
Overall 3-group ANOVA 
Effect  
            DF [2]        SE [2]       Statistics [2]     p-value [2] 
Treatment 
nn 
xx.xx         xx.xx               0.xxxx 
Time                
nn 
xx.xx         xx.xx               0.xxxx 
Treat*Time             nn 
xx.xx         xx.xx               0.xxxx 
Baseline TPS 
nn 
xx.xx 
   xx.xx           0.xxxx 
Asthma  
nn 
xx.xx 
   xx.xx              0.xxxx 
Combined Treatment 2-group ANOVA 
 
DF [4] 
SE [4] 
Statistics [4]         p-value [4]     
nn 
xx.xx         xx.xx                 0.xxxx 
nn 
xx.xx   
  xx.xx 
            0.xxxx 
nn 
xx.xx 
  xx.xx                 0.xxxx 
nn 
xx.xx 
   xx.xx             0.xxxx 
nn 
xx.xx 
   xx.xx             0.xxxx 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 89 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.9.8 
Total Polyp Score (TPS) – Time to Response at Any Time 
MITT Population 
 
Response Criteria 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined [4] 
(N=  ) 
 
 
 
 
1-point Reduction Response [1] 
Yes 
No 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
   Time to Response (days) 
 
 
 
 
Mean (SD) 
Median 
Min, Max 
xx.x (xx.xx) 
xx.x 
xx.x, xx.x 
xx.x (xx.xx) 
xx.x 
xx.x, xx.x 
xx.x (xx.xx) 
xx.x 
xx.x, xx.x 
xx.x (xx.xx) 
xx.x 
xx.x, xx.x 
25th – 75th Percentile 
p-value  
xx.x - xx.x 
 
xx.x - xx.x 
0.xxxx [2] 
 
xx.x - xx.x 
0.xxxx [2] 
 
xx.x - xx.x 
0.xxxx [4] 
 
      HR (95% CI)  
      p-value  
 
xx.x (xx.x – xx.x) [3] 
0.xxxx [3] 
xx.x (xx.x – xx.x) [3] 
0.xxxx [3] 
xx.x (xx.x – xx.x) [4] 
0.xxxx [4] 
 
 
 
 
50% Reduction Response 
… 
 
 
 
 
 
 
 
 
 
[1] Response is defined as 1-point or50% reduction in TPS score. Any subject who does not provide an assessment at the specified time point for defining response will be 
considered to be a non-responder.  
[2] p-value is from the log-rank test. 
[3] HR, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a Cox PH model. 
[4] Similar analysis as described above in [2] and [3] is performed for the combined AK001 groups vs. Placebo. 
 
path\t_program.sas date 
time 
 
Programming note:Table will include the following responses: 1-point Reduction,  and 50% Reduction, where response is defined as 1-point, and 50% reduction in TPS score, 
respectively.  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 90 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.10.1 
Subgroup Analysis of TPS Score at Week 12 by Gender  
MITT Population 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment and asthma status (stratification factor). Baseline TPS score was included as a covariate. An unstructured covariance model was used.   
[3] Results are from contrast statement in the model descirbed in footnote [2]. 
[4] This analysis is performed similar to the model described in footnote [2] (AK001 dose levels are combined into one group vs. placebo).   
 [5] p-values are from a restricted maximum likelihood based repeated measures linear mixed model with fixed effects for treatment, gender, treatment*gender interaction, and 
asthma status (stratification factor). Baseline TPS score was included as a covariate. An unstructured covariance model was used. Should unstructured covariance model not 
coverge, compound symmetry will be used instead. 
[6] This analysis is performed similar to the model described in footnote [5] (AK001 dose levels are combined into one group vs. placebo).  
 
Subgroup  
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined [4] 
(N=  ) 
p-value for 
Gender Effect  
p-value for Treatment 
by Gender Interaction 
 
 
 
 
 
 
Male 
Change from Baseline[1] to Week 12 
 
 
 
 
0.xxxx [5] 
0.xxxx [5] 
 
n 
n 
n 
n 
n 
0.xxxx [6] 
0.xxxx [6] 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
LS Mean  
xx.x [2] 
xx.x [2] 
xx.x [2] 
xx.x [4] 
 
 
   95% CI  
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [4] 
 
 
 
 
 
 
 
 
   LS Mean Difference (AK001 – Placebo)  
 
xx.x [3] 
xx.x [3] 
xx.x [4] 
 
 
 
    95% CI 
 
(xx, xx) [3] 
(xx, xx) [3] 
(xx, xx) [4] 
 
 
   p-value  
 
0.xxxx [3] 
0.xxxx [3] 
0.xxxx [4] 
 
 
 
 
 
 
 
 
 
 
Female 
Change from Baseline[1] to Week 12 
 
 
 
 
 
 
 
n 
n 
n 
n 
n 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
LS Mean  
xx.x [2] 
xx.x [2] 
xx.x [2] 
xx.x [4] 
 
 
   95% CI  
(xx, xx) [2]  
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [4] 
 
 
 
 
 
 
 
 
   LS Mean Difference (AK001 – Placebo)  
 
xx.x [3] 
xx.x [3] 
xx.x [4] 
 
 
 
    95% CI [2] 
 
(xx, xx) [3] 
(xx, xx) [3] 
(xx, xx) [4] 
 
 
   p-value [2]  
 
0.xxxx [3] 
0.xxxx [3] 
0.xxxx [4] 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 91 of 175 
CONFIDENTIAL 
 
 
path\t_program.sas date 
time   
 
Programming note: Repeat this table for all subgroups as follows: 
Table 14.2.10.2 for Subgroup Analysis of TPS Score at Week 12 by Age(< Median, ≥ Median) 
Table 14.2.10.3 for Subgroup Analysis of TPS Score at Week 12 by Asthma (Yes, No) 
Table 14.2.10.4 for Subgroup Analysis of TPS Score at Week 12 by 1-point reduction responder criteria 
Table 14.2.10.5 for Subgroup Analysis of TPS Score at Week 12 by 20% reduction responder criteria 
Table 14.2.10.6 for Subgroup Analysis of TPS Score at Week 12 by 30% reduction responder criteria 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 92 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.11 
Change in Size of Polyps (Lund-Mackay Score) from Baseline to Week 12 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment and asthma status (stratification factor). Baseline Lund-Mackay score was included as a covariate. An unstructured covariance model was used. 
[3] Results are from contrast statement in the model described above. 
Score Component 
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined [4] 
(N= ) 
Maxillary 
Baseline [1] 
 
 
 
 
 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Week 12 
 
 
 
 
 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Change from Baseline to Week 12 
 
 
 
 
 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
LS Mean  
xx.x [2] 
xx.x [2] 
xx.x [2] 
xx.x [4] 
   95% CI  
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [4] 
 
 
 
 
   LS Mean Difference (AK001 vs. Placebo) 
 
xx.x [3] 
xx.x [3] 
xx.x [4] 
 
    95% CI  
 
(xx, xx) [3] 
(xx, xx) [3] 
(xx, xx) [4] 
   p-value  
 
0.xxxx [3] 
0.xxxx [3] 
0.xxxx [4] 
 
Anterior Ethmoid 
… 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 93 of 175 
CONFIDENTIAL 
 
 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
 
path\t_program.sas date 
time   
 
Programming note: Table will include the following Lund-Mackay score components: Maxillary, Anterior ethmoid, Posterior ethmoid, Sphenoid, Frontal, Osteomeatal complex, 
and Total score. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 94 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.12.1  
Change in Peak Nasal Inspiration Flow (PNIF) from Baseline over Time 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction, and asthma status (stratification factor). Baseline PNIF was included as a covariate. An unstructured covariance 
model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1. 
Table will include the following raw score visits: Baseline,  Week 3, Week 12 and Week 16; and change from baseline for Week 3, Week 12 and Week 16.   
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 95 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.12.2  
Peak Nasal Inspirational Flow (PNIF) – Time to Response at Any Time 
MITT Population 
 
 
[1] Response is defined as 50% reduction in PNIF score. Any subject who does not provide an assessment at the specified time point for defining response will be considered to be a 
non-responder.  
[2] p-value is from the log-rank test. 
[3] HR, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a Cox PH model. 
[4] Similar analysis as described above in [2] and [3] is performed for the combined AK001 groups vs. Placebo. 
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.8. 
Table will include the following response: 50% Reduction, where response is defined as 50% reduction in PNIF score.  
  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 96 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.13.1  
Change in Sense of Smell (UPSIT Total Score) from Baseline over Time 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction, and asthma status (stratification factor). Baseline UPSIT score was included as a covariate. An unstructured 
covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
Missing data was assumed to be a wrong response and no imputation was performed to replace.  
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1.  
Table will include the following raw score visits: Baseline,  Week 2, Week 3, Week 7, Week 12 and Week 16; and change from baseline for Week 2, Week 3, Week 7, Week 12 and 
Week 16.  If feasible, repeat table by each odorant.  
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 97 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.13.2 
Sense of Smell (UPSIT) – Time to Response at Any Time 
MITT Population 
 
 
[1] Response is defined as 50% reduction in UPSIT score. Any subject who does not provide an assessment at the specified time point for defining response will be considered to be 
a non-responder.  
[2] p-value is from the log-rank test. 
[3] HR, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a Cox PH model. 
[4] Similar analysis as described above in [2] and [3] is performed for the combined AK001 groups vs. Placebo. 
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.8. 
Table will include the following response: 50% Reduction, where response is defined as 50% reduction in UPSIT score.  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 98 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.14.1 
 
Sino-nasal Outcome Test-22 (SNOT-22) (Five Most Important Items) at Week 12 
MITT Population 
 
 
[1] Number (%) are based on the number of subjects that have picked the category as one of the five most important items. 
Missing data was imputed by the average score of the items present.   
 
path\t_program.sas date 
time   
Programming note: Table will include all 22 items in Appendix F.   
 
Item 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
 
 
 
 
Need to blow nose 
   n (%) [1] 
n (%) 
n (%) 
n (%) 
Nasal blockage 
Sneezing 
Runny nose 
Cough 
Post-nasal discharge 
Thick nasal discharge 
Ear fullness 
Dizziness 
Ear pain 
Facial pain/pressure 
… 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 99 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.14.2  
Change in SNOT-22 (Total Score of Five Most Important Items) from Baseline over Time 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction, and asthma status (stratification factor). Baseline SNOT-22 score was included as a covariate. An unstructured 
covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
Missing data was imputed by the average score of the items present.   
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1. 
Table will include the following raw score visits: Baseline,  Week 2, Week 3, Week 7, Week 12 and Week 16; and change from baseline for Week 2, Week 3, Week 7, Week 12 and 
Week 16.   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 100 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.14.3  
Change in SNOT-22 (Total Score of All Items) from Baseline over Time 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction, and asthma status (stratification factor). Baseline SNOT-22 score was included as a covariate. An unstructured 
covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
Missing data was imputed by the average score of the items present.   
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1.  
Table will include the following raw score visits: Baseline,  Week 2, Week 3, Week 7, Week 12 and Week 16; and change from baseline for Week 2, Week 3, Week 7, Week 12 and 
Week 16.   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 101 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.14.4  
Sino-nasal Outcome Test-22 (SNOT-22) – Time to Response at Any Time 
MITT Population 
 
 
[1] Response is defined as 50% reduction in SNOT-22 score. Any subject who does not provide an assessment at the specified time point for defining response will be considered to 
be a non-responder.  
[2] p-value is from the log-rank test. 
[3] HR, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a Cox PH model. 
[4] Similar analysis as described above in [2] and [3] is performed for the combined AK001 groups vs. Placebo. 
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.8. 
Table will include the following response: 50% Reduction, where response is defined as 50% reduction in SNOT-22 score.  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 102 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.15.1 
Visual Analogue Scale (VAS) by Symptom  
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] The symptomatology can be divided into “mild’, “moderate”, and “severe” categories based on total score: Mild=0,1,2; Moderate=3,4,5,6; Severe=7,8,9,10 
Missing data was imputed by the average score of the non-missing values.   
 
path\t_program.sas date 
time   
 
Programming note: Table will include the following symptoms of rhinosinusitis: Anterior nasal discharge, Posterior nasal discharge, Nasal congestion, blockade, or obstruction, 
Decreased sense of smell, Facial pain or pressure. 
 
 
Symptom 
Severity 
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
Anterior Nasal Discharge 
Mild[2] 
Baseline [1] 
Week 12 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
Moderate[2] 
Baseline [1] 
Week 12 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
Severe[2] 
Baseline [1] 
Week 12 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
Posterior Nasal Discharge 
… 
 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 103 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.15.2 
Change in Visual Analogue Scale (VAS by Symptom) from Baseline over Time 
MITT Population 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction and asthma status (stratification factor) . Baseline VAS score was included as a covariate. An unstructured 
covariance model was used. 
Symptom 
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined [4] 
(N= ) 
Anterior Nasal Discharge 
Baseline [1] 
 
 
 
 
 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Week 12 
 
 
 
 
 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Change from Baseline to Week 12 
 
 
 
 
 
n 
n 
n 
n 
n 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
LS Mean  
xx.x [2] 
xx.x [2] 
xx.x [2] 
xx.x [4] 
   95% CI  
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [2] 
(xx, xx) [4] 
 
 
 
 
   LS Mean Difference (AK001 vs. Placebo) 
 
xx.x [3] 
xx.x [3] 
xx.x [4] 
 
    95% CI  
 
(xx, xx) [3] 
(xx, xx) [3] 
(xx, xx) [4] 
   p-value  
 
0.xxxx [3] 
0.xxxx [3] 
0.xxxx [4] 
 
Posterior Nasal Discharge 
… 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 104 of 175 
CONFIDENTIAL 
 
 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
Missing data was imputed by the average score of the non-missing values.   
 
path\t_program.sas date 
time   
 
Programming note: Table will include the following symptom of rhinosinusitis: Anterior nasal discharge, Posterior nasal discharge, Nasal congestion, blockade, or obstruction, 
Decreased sense of smell, and Facial pain or pressure. 
Programming note: Table will include the following raw score visits: Baseline,  Week 2, Week 3, Week 7, Week 12 and Week 16; and change from baseline for Week 2, Week 3, 
Week 7, Week 12 and Week 16.   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 105 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.15.3  
Change in Visual Analogue Scale (VAS Total Score) from Baseline over Time 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction and asthma status (stratification factor). Baseline VAS score was included as a covariate. An unstructured 
covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
Missing data was imputed by the average score of the non-missing values.    
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1. 
Table will include the following raw score visits: Baseline,  Week 2, Week 3, Week 7, Week 12 and Week 16; and change from baseline for Week 2, Week 3, Week 7, Week 12 and 
Week 16.   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 106 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.15.4  
Visual Analogue Scale (VAS) – Time to Response at Any Time 
MITT Population 
 
 
[1] Response is defined as 50% reduction in VAS score. Any subject who does not provide an assessment at the specified time point for defining response will be considered to be a 
non-responder.  
[2] p-value is from the log-rank test. 
[3] HR, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a Cox PH model. 
[4] Similar analysis as described above in [2] and [3] is performed for the combined AK001 groups vs. Placebo. 
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.8. 
Table will include the following response: 50% Reduction, where response is defined as 50% reduction in VAS score.  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 107 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.15.5  
Change in Clinical Symptoms Improvement Scale (Total Score) from Baseline over Time 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction and asthma status (stratification factor). Baseline Clinical Symptoms Improvement Scale score was included as a 
covariate. An unstructured covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
In case of Visit-Baseline, negative difference means improvement. 
Missing data was imputed by the average score of the non-missing values.    
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1. 
Table will include the following raw score visits: Baseline,  Week 2, Week 3, Week 7, Week 12 and Week 16; and change from baseline for Week 2, Week 3, Week 7, Week 12 and 
Week 16.   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 108 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.16  
Change in 36-Item Short Form Health Survey (SF-36 Total Score) from Baseline over Time 
MITT Population 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction and asthma status (stratification factor). Baseline SF-36 score was included as a covariate. An unstructured 
covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
Missing data was imputed by the average score of the category that the question belongs to.    
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1. 
Table will include the following raw score visits: Baseline,  Week 3, Week 7, Week 12 and Week 16; and change from baseline for Week 3, Week 7, Week 12 and Week 16.   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 109 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.17.1  
Biomarker Analysis: Change in Biomarkers from Baseline over Time 
Biomarker Population, Sub-Study 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment, time, treatment*time interaction, and asthma status (stratification factor). Baseline Biomarker level was included as a covariate. An unstructured 
covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
 
 
Footnote: The content of this table is only a placeholder until we see the Biomarker test data 
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.9.1. 
Table will include the following raw score visits: Baseline,  Week 2, Week 3, Week 7, and Week 16; and change from baseline for Week 2, Week 3, Week 7, and Week 16.   
Table will include the following biomarkers: Eosinophilic Cationic Protein(µg/L), Histamin (ng/mL), Tryptase(ng/mL), Prostaglandins(pg/mL), Leukotrienes(pg/mL), 
Chymase(ng/mL), Carboxypeptidase A3(mg), Cytokines(mg), Chemokines (including Interleukin-5(ng/mL), Interleukin-17(ng/mL), Interferon(ng/mL), Interleukin-4(ng/mL), 
Interleukin-13(ng/mL), Thymic Stromal Lymphopoietin(ng/mL), Interleukin-33(ng/mL), Interleukin-8(ng/mL)), Tumor Necrosis Factor(ng/mL), Albumin(µg/dL), 
Myeloperoxidase(unit/mL), Growth Factors. 
 
Repeat Table 14.2.17.2 for Biomarker Analysis: Percent Change in Biomarkers from Baseline over Time (Biomarker Population, Sub-Study)   
Repeat Table 14.2.17.3 for Biomarker Analysis: Change in Biomarkers from Baseline over Time (Biomarker Population, All Patients)  
Repeat Table 14.2.17.4 for Biomarker Analysis: Percent Change in Biomarkers from Baseline over Time (Biomarker Population, All Patients) 
Programming note: Tables 14.2.17.3 and 14.2.17.4 will include the following raw score visits: Baseline, Week 3, Week 7 and Week 12; and change from baseline for Week 3, 
Week 7 and Week 12. Tables 14.2.17.3 and 14.2.17.4 will include the following inflammatory responses:Eosinophils (109 /L), Mast Cells (109 /L), Basophils (109 /L). 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 110 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.18.1  
Change in Forced Expiratory Volume in 1 Second (FEV1) from Baseline to Week 7 
MITT Population in Patients with Comorbid Asthma 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
[2] LS means, 95% CIs, and p-values comparing AK001 treatment groups to placebo group are from a restricted maximum likelihood based repeated measures linear mixed model 
with fixed effects for treatment. Baseline FEV1 was included as a covariate. An unstructured covariance model was used. 
[3] Results are from contrast statement in the model described above. 
[4] This analysis is performed similar to the model above (AK001 dose levels are combined into one group vs. placebo).   
 
path\t_program.sas date 
time   
 
Programming note: This table is same as Table 14.2.8.1. 
Programming note: do not include asthma as a covariate. 
Programming note: Repeat the following tables --- 
             Table 14.2.18.2 Change in Forced Vital Capacity (FVC) from Baseline to Week 7 
            Table 14.2.18.3 Change in Forced Expiratory Flow (FEF) from Baseline to Week 7 
           Table 14.2.18.4 Change in Asthma Control Test (ACT) from Baseline to Week 12   
                                 
                        
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 111 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.18.5.1 
Use of Asthma Rescue Therapy[1] from Baseline to Week 12 
MITT Population in Patients with Comorbid Asthma 
 
 
  
[1] Question ACT4 from the ACT questionnaire. Daily User (3 or more times per day; 1 or 2 times per day); Weekly User (2 or 3 times per week; once a week or less); Non-User 
(Not at all). 
[2] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
 
 
Time Point 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N= ) 
AK001 
Combined 
(N= ) 
 
 
 
 
Baseline [2] 
 
 
 
 
Daily user 
n (%) 
n (%) 
n (%) 
n (%) 
Weekly user 
Non-user 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
Week 12 
 
 
 
 
Daily user 
n (%) 
n (%) 
n (%) 
n (%) 
Weekly user 
Non-user 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 112 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.2.18.5.2 
Use of Asthma Rescue Therapy[1] – Shift from Baseline to Week 12 
MITT Population in Patients with Comorbid Asthma 
 
Placebo 
(N=   ) 
Baseline [2] 
 
AK001 
25 mg 
(N=   ) 
Baseline [2] 
 
AK001 
250 mg 
(N=  ) 
Baseline [2] 
 
AK001 
Combined 
(N=  ) 
Baseline [2 
Target Visit 
Daily 
 user 
Weekly  
user 
 
Non-user 
 
Missing 
 
Daily 
user 
Weekly  
user 
 
Non-user 
 
Missing 
 
Daily  
user 
Weekly  
user 
 
Non-user 
 
Missing 
 
Daily  
user 
Weekly  
user 
 
Non-user 
 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Daily user 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
  Weekly user 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Non-user 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
   Missing 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Question ACT4 from the ACT questionnaire . Daily User (3 or more times per day; 1 or 2 times per day); Weekly User (2 or 3 times per week; once a week or less); Non-User 
(Not at all). 
[2] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 113 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.1.19.1 
Overall Summary of All Adverse Events  
Safety Population  
 
Placebo 
(N= ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
 
 
 
 
Subjetcs with any AE 
n (%) 
n (%) 
n (%) 
n (%) 
Aubjects with any non-TEAE 
n(%) 
n (%) 
n (%) 
n (%) 
Subjects with any TEAE 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any Severe TEAE 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any TEAE Related to Study Drug [1] 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any Serious TEAE 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any TEAE with Outcome of Death 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any Treatment-Emergent AESI 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any TEAE Leading to Dose Reduction 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any TEAE Leading to Dose Interruption 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any TEAE Leading to Study Drug Withdrawal 
n (%) 
n (%) 
n (%) 
n (%) 
Subjects with any TEAE Leading to Dose Reduction, Interruption, or Withdrawal 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Total Number of TEAE 
n 
n 
n 
n 
Total Number of Severe TEAE 
n 
n 
n 
n 
Total Number of TEAE Related to Study Drug [1] 
n 
n 
n 
n 
Total Number of Serious TEAE 
n 
n 
n 
n 
Total Number of TEAE with Outcome of Death 
n 
n 
n 
n 
Total Number of TEAE Leading to Dose Reduction 
n 
n 
n 
n 
Total Number of TEAE Leading to Dose Interruption 
n 
n 
n 
n 
Total Number of TEAE Leading to Study Drug Withdrawal 
n 
n 
n 
n 
Total Number of TEAE Leading to Dose Reduction, Interruption, or Withdrawal 
n 
n 
n 
n 
 
 
 
 
 
[1] Includes all events reported as “Possibly Related” or “Related” to study drug. 
 
path\t_program.sas date 
time 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 114 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.1.19.2.1 
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class / 
Preferred Term 
Placebo 
(N=   ) 
 
AK001 
25 mg 
(N=   ) 
 
AK001 
250 mg 
(N=  ) 
 
AK001 
Combined 
(N=  ) 
Subjects [1] 
Events 
 
Subjects [1] 
Events 
 
Subjects [1] 
Events 
 
Subjects [1] 
Events 
 
 
 
 
 
 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
. 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
[1] At each level of summation (overall, system organ class, preferred term), subjects reporting more than one adverse event are counted only once.  
 
path\t_program.sas date 
time   


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 115 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.1.19.2.2 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Severity 
Safety Population 
 
System Organ Class / 
Preferred Term 
Placebo 
(N=   ) 
 
AK001 
25 mg 
(N=   ) 
 
AK001 
250 mg 
(N=  ) 
 
AK001 
Combined 
(N=  ) 
Mild 
Moderate Severe 
Missing 
 
Mild 
Moderate Severe Missing  
Mild 
Moderate Severe Missing  
Mild Moderate Severe Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Preferred Term 1 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Preferred Term 2 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Preferred Term 1 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Preferred Term 2 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
To be continued on Page 2 for “All Active AK001” group 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: At each level of summation (overall, system organ class, preferred term), subjects reporting more than one adverse event are counted only once using the worst severity. 
path\t_program.sas date 
time   


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 116 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.1.19.2.3 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Relationship to Study Drug 
Safety Population 
 
System Organ Class /  
  Preferred Term 
Placebo 
(N=   ) 
 
AK001 
25 mg 
(N=   ) 
 
AK001 
250 mg 
(N=  ) 
 
AK001 
Combined 
(N=  ) 
Related [1] 
Not Related [2] 
 
Related [1] 
Not Related [2] 
 
Related [1] 
Not Related [2] 
 
Related [1] 
Not Related [2] 
 
 
 
 
 
 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
Preferred Term 1 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
Preferred Term 2 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
. 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
Preferred Term 1 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
Preferred Term 2 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
 
n (%) 
n (%) 
Note: At each level of summation (overall, system organ class, preferred term), subjects reporting more than one adverse event are counted only once using the strongest 
relationship to study drug. 
[1] Includes all events reported by the Investigator as “Possibly Related,” or “Related” to study drug. 
[2] Includes all events reported by the Investigator as “Unlikely Related” or “Not Related” to study drug. 
 
path\t_program.sas date 
time   


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 117 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.2.19.3 
Treatment-Emergent Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class / 
Preferred Term 
Placebo 
(N=   ) 
 
AK001 
25 mg 
(N=   ) 
 
AK001 
250 mg 
(N=  ) 
 
AK001 
Combined 
(N=  ) 
Subjects [1] 
Events 
 
Subjects [1] 
Events 
 
Subjects [1] 
Events 
 
Subjects [1] 
Events 
 
 
 
 
 
 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
. 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
[1] At each level of summation (overall, system organ class, preferred term), subjects reporting more than one adverse event are counted only once.  
 
path\t_program.sas date 
time   
 
Programming note: Repeat table for the tables listed below 
 
Table 14.3.2.19.4.1 
Treatment-Emergent Fatal Serious Adverse Events by System Organ Class and Preferred Term (Safety Population) 
Table 14.3.2.19.4.2 
Treatment-Emergent Non-Fatal Serious Adverse Events by System Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.19.5 
Treatment-Emergent Severe Adverse Events by System Organ Class and Preferred Term (Safety Population) 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 118 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.1.19.6 
Day 0 Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class /  
  Preferred Term 
Placebo 
(N=   ) 
 
AK001 
25 mg 
(N=   ) 
 
AK001 
250 mg 
(N=  ) 
 
AK001 
Combined 
(N=  ) 
Subjects [1] Events  Subjects [1] Events  Subjects [1] Events 
 Subjects [1] Events 
 
 
 
 
 
 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
. 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
[1] At each level of summation (overall, system organ class, preferred term), subjects reporting more than one adverse event are counted only once.  
Note: Day-0 TEAEs, defined as all TEAEs occurring on the same calendar day as dosing (Day 0) with an onset on or after the time of the first dose of study drug. 
 
path\t_program.sas date 
time   
 
Programming note: This table needs to be stand alone and every table after this one should be renumbered. 
 
 
 
 
 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 119 of 175 
CONFIDENTIAL 
 
 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.1.19.7 
Post-Treatment Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class /  
  Preferred Term 
Placebo 
(N=   ) 
 
AK001 
25 mg 
(N=   ) 
 
AK001 
250 mg 
(N=  ) 
 
AK001 
Combined 
(N=  ) 
Subjects [1] Events 
 Subjects [1] 
Events 
 
Subjects [1] Events  Subjects [1] 
Events 
 
 
 
 
 
 
 
 
 
 
 
Subjects Reporting at Least One Adverse Event 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
. 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 1 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
Preferred Term 2 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
n (%) 
n 
 
 [1] At each level of summation (overall, system organ class, preferred term), subjects reporting more than one adverse event are counted only once.  
Note: Post-treatment adverse events are defined as TEAEs that have an onset more than 7 days after the last dose of study drug. 
 
path\t_program.sas date 
time 
 
Programming note: Repeat table for the tables listed below 
 
 
Table 14.3.1.19.8.1 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety Population Subgroup: Asthma Present) 
Table 14.3.1.19.8.2 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety Population Subgroup: Asthma Absent) 
Table 14.3.1.19.8.3 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety Population Subgroup: Using Concomitant Medication at Any Time During the 
Study) 
Table 14.3.1.19.8.4 
Treatment-Emergent Adverse Events by SOC and Preferred Term (Safety Population Subgroup: Not Using Concomitant Medication at Any Time During the 
Study) 
Table 14.3.1.19.8.5 
Treatment-Emergent Adverse Events by SOC and Preferred Term in at least 5 Subjects in any of Treatment Group (Safety Population) 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 120 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.20.1.1 
Hematology Values and Changes from Baseline at All Visits – Conventional Units 
Safety Population 
 
Laboratory Parameter 
Target Visit 
Placebo 
(N=   ) 
AK001 
25 mg 
(N=  ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
 
 
 
 
WBC (109 /L) 
Baseline [1] 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Week 2 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Change from Baseline to Week 2 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
… 
 
 
 
 
Neutrophils (109 /L) 
 
 
 
 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
path\t_program.sas date 
time   
 
Programming note: Table will include all hematology parameters collected from Central Laboratory, and all target visits (Week 2, Week 3,  Week 7, Week 12, and Week 16) and 
for Last Available On-Treatment Value. Please see Appendix A for visit windows.  
Repeat for Table 14.3.4.20.1.2 using SI Units. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 121 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.20.1.3 
Hematology – Shift from Baseline 
Safety Population 
 
 
Placebo 
(N=   ) 
Baseline [1] 
AK001 
25 mg 
(N=   ) 
Baseline [1] 
AK001 
250 mg 
(N=  ) 
Baseline [1] 
AK001 
Combined 
(N=  ) 
Baseline [1] 
Laboratory Parameter Target Visit 
Low Normal High Missing  
Low 
Normal 
High Missing  
Low 
Normal 
High 
Missing  
Low 
Normal High Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WBC 
Week 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Normal 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
High 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Missing 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Normal 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
High 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Missing 
n (%) n (%) n (%) n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neutrophils 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include all hematology parameters collected from Central Laboratory and all target visits (Week 2,  Week 3, Week 7, Week 12, and Week 16) and 
for Last Available On-Treatment Value. Please see Appendix A for visit windows. 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 122 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.20.2.1 
Serum Chemistry Values and Changes from Baseline at All Visits – Conventional Units 
Safety Population 
 
Laboratory Parameter Target Visit 
Placebo 
(N=   ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=   ) 
AK001 
Combined 
(N=   ) 
 
 
 
 
ALT (SGPT) (U/L) 
Baseline [1] 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Week 2 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Change from Baseline to Week 2 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
… 
 
 
 
 
AST (SGOT) (U/L) 
 
 
 
 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
Programming note: Table will include all serum chemistry parameters collected by Central Laboratory and all target visits (Week 2,  Week 3,  Week 7, Week 12, and Week 16) and 
for Last Available On-Treatment Value. Please see Appendix A for visit windows.  
Repeat for Table 14.3.4.20.2.2 using SI Units. 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 123 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.20.2.3 
Serum Chemistry – Shift from Baseline 
Safety Population 
 
Placebo 
(N=   ) 
Baseline [1] 
 
AK001 
25 mg 
(N=   ) 
Baseline [1] 
 
AK001 
250 mg 
(N=  ) 
Baseline [1] 
 
AK001 
Combined 
(N= ) 
Baseline [1] 
Laboratory Parameter Target Visit 
Low Normal 
High 
Missing 
 
Low 
Normal 
High 
Missing  Low Normal High 
Missing 
 
Low 
Normal High 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT(SGPT) 
Week 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Normal 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
High 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Missing 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Normal 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
High 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Missing 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 n (%) n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AST (SGOT) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include all serum chemistry parameters collected by Central Laboratory and all target visits (Week 2,  Week 3,  Week 7, Week 12, and Week 16) and 
for Last Available On-Treatment Value. Please see Appendix A for visit windows. 
Missing category was present. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 124 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.20.3.1 
Urinalysis Values at All Visits  
Safety Population 
 
Laboratory Parameter 
Target Visit 
Placebo 
(N=   ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
 
 
 
 
pH 
Baseline [1] 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Week 2 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Change from Baseline to Week 2 
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
… 
 
 
 
 
 
 
 
 
Specifc Gravity 
 
 
 
 
 
 
 
 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include pH and specific gravity using descriptive statistics at baseline and at each post-baseline time point for all target visits (Week 2, Week 7, 
Week 12, and Week 16) and for Last Available On-Treatment Value. Please see Appendix A for visit windows.  


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 125 of 175 
CONFIDENTIAL 
 
 
Table will also include Categorical Laboratory Parameters, summarized by treatment group for each target week using counts and percent of subjects in each result category. 
Instead of mean, median, min, max, use the lab reported values (for example, 0, trace, +1, +2, etc). For these categorical laboratory parameters, no change from baseline will be 
displayed in the table. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 126 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.20.3.2.1 
Urinalysis – Shift from Baseline 
Part 1 of  2 
Safety Population 
 
Placebo 
(N=   ) 
Baseline [1] 
 
AK001 
25 mg 
(N=   ) 
Baseline [1] 
 
AK001 
250 mg 
(N=  ) 
Baseline [1] 
 
AK001 
Combined 
(N=  ) 
Baseline [1] 
Laboratory Parameter Target Visit Low Normal 
High 
Missing 
 
Low 
Normal 
High 
Missing  
Low Normal High 
Missing 
 
Low 
Normal High Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PH 
Week 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Normal n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
High 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Missing n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Normal n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
High 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
Missing n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
 
n (%) n (%) n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specific Gravity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include only pH and specific gravity collected by Central Laboratory and all target visits (Week 2,  Week 7, Week 12, and Week 16) and for Last 
Available On-Treatment Value. Please see Appendix A for visit windows. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 127 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.20.3.2.2 
Urinalysis – Shift from Baseline 
Part 2 of 2 
Safety Population 
 
 
Placebo 
(N=   ) 
Baseline [1] 
 
AK001 
25 mg 
(N=   ) 
Baseline [1] 
 
AK001 
250 mg 
(N=  ) 
Baseline [1] 
 
AK001 
Combined 
(N=  ) 
Baseline [1] 
Laboratory Parameter Target Visit 
Negative 
Positive 
Missing 
 
Negative 
Positive 
Missing 
 
Negative 
Positive 
Missing 
 
Negative 
Positive 
Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
Week 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
Positive 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
Missing 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
Positive 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
Missing 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ketones 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include categorical laboratory parameters collected by Central Laboratory and all target visits (Week 2,  Week 7, Week 12, and Week 16) and for 
Last Available On-Treatment Value. Please see Appendix A for visit windows. Instead of low, normal, high, use negative, positive categories.  
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 128 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.21.1 
Vital Signs – Day 0 Pre-Dose and Post-Dose 
Safety Population 
 
Vital Sign 
Time Point 
Placebo 
(N=   ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
 
 
 
 
Systolic BP (mmHg) 
Day 0 Pre-Dose [1]  
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
Day 0 Post-Dose [2] 
 
 
 
 
… 
 
 
 
 
Change from Baseline to Day 0 Post-Dose 
 
 
 
 
… 
 
 
 
 
 
 
 
 
Diastolic BP (mmHg) 
… 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
[1] Day 0 Pre-Dose is defined as the pre-dose value on Day 0. 
[2] Day 0 Post-Dose is approximately 15 min after post-dose. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include the following vital signs: systolic BP (mmHg), diastolic BP (mmHg), pulse rate (beats/min), body temperature (°C) and respiration rate 
(breaths/ min).  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 129 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.21.2 
Vital Signs – Screening and Post Day 0 
Safety Population 
 
Vital Sign 
Target Visit 
Placebo 
(N=   ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
 
 
 
 
Systolic BP (mmHg) 
Screening  
 
 
 
 
n 
n 
n 
n 
n 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx, xx 
 
 
 
 
Baseline [1] 
 
 
 
 
… 
 
 
 
 
Week 2 
 
 
 
 
… 
 
 
 
 
Change from Baseline to Week 2 
 
 
 
 
… 
 
 
 
 
 
 
 
 
Diastolic BP (mmHg) 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last non-missing value prior to first dose of study drug. 
 
path\t_program.sas date 
time   
 
Programming note: Table will include the following vital signs: systolic BP (mmHg), diastolic BP (mmHg), pulse rate (beats/min), body temperature (°C) and respiration rate 
(breaths/ min) for the following target visits: Screening, Baseline, Week 2,  Week 3, Week 7, Week 12, and Week 16, and for Last Available On-Treatment Value. Please see 
Appendix A for visit windows. 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 130 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Table 14.3.4.21.3 
Incidence of Potentially Clinically Significant Vital Sign Results 
Safety Population 
 
Any Post-Baseline  
Clinically Significant Abnormalities? 
Potentially Clinically 
Significant Criteria 
Target Visit 
Placebo 
(N=   ) 
AK001 
25 mg 
(N=   ) 
AK001 
250 mg 
(N=  ) 
AK001 
Combined 
(N=  ) 
 
 
 
 
Systolic Blood Pressure 
Criteria  
Baseline 
n (%) 
n (%) 
n (%) 
n (%) 
     
Any Post-Baseline Visit 
n (%) 
n (%) 
n (%) 
n (%) 
 
Day 0 Post-Dose 
n (%) 
n (%) 
n (%) 
n (%) 
 
Week 2 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
 
 
 
 
 
Diastolic Blood Pressure 
Criteria  
Baseline 
n (%) 
n (%) 
n (%) 
n (%) 
 
Any Post-Baseline Visit 
n (%) 
n (%) 
n (%) 
n (%) 
 
Day 0 Post-Dose 
n (%) 
n (%) 
n (%) 
n (%) 
 
Week 2 
n (%) 
n (%) 
n (%) 
n (%) 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
path\t_program.sas date 
time   
 
Programming note: Table will include all parameters (systolic BP (mmHg), diastolic BP (mmHg), pulse rate(beats/min), body temperature (°C) and respiration rate 
(breaths/min)) with defined potentially clinically significant ranges at each post-Baseline visit.  Target visits for all parameters after Day 0 are: Week 2,  Week 3, Week 7, Week 
12, and Week 16. Please see Appendix A for visit windows. 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 131 of 175 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix J:  Figure Layouts 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
 
Figure 
Figure 14.2.1.1 
Title 1 
Least Squares Mean Change in Total Polyp Score (TPS)   
Title 2  
MITT Population 
Type of graph 
Line Graph 
y-axis 
Mean Change in TPS 
y-axis (label) 
Least Squares Mean Change (95% CI) in TPS 
x-axis 
3, 7, 12, 16 Weeks (programming note: time points will change with different efficacy outcomes) 
x-axis (label) 
Time Point 
Legend 
No. of patients 
    AK001 25 mg          n    n    n    n 
    AK001 250 mg        n    n    n    n 
    AK001 Combined    n    n    n    n 
    Placebo                     n    n    n    n 
Footnotes 
Note: Bars represent 95% CIs. 
          Figure corresponds to Table 9.1  
 
path\t_program.sas date 
time   
Additional information 
Plot Least Squares Mean Change from Baseline and 95% CIs.  
Repeat Figure 14.2.1.2 – Mean Change in Total Polyp Score (TPS) (MITT Population in Patients with Cormobid Asthma) 
Repeat Figure 14.2.2 – Mean Change in Peak Nasal Inspiratory Flow (PNIF) (MITT Population) 
Repeat Figure 14.2.3 – Mean Change in University of Pennsylvania Smell Identification Test (UPSIT) (MITT Population) 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 132 of 175 
CONFIDENTIAL 
 
 
Repeat Figure 14.2.4 – Mean Change in 22-item Sinonasal Outcome Test (SNOT-22) (MITT Population) 
Repeat Figure 14.2.5 – Mean Change in Visual Analogue Scale (VAS) (MITT Population) 
Repeat Figure 14.2.6 – Mean Change in Forced Expiratory Volume in 1 Second (FEV1) (MITT Population in Patients with Cormobid Asthma) 
Repeat Figure 14.2.7 – Mean Change in Asthma Control Test (ACT) (MITT Population in Patients with Cormobid Asthma) 
Repeat Figure 14.2.8 – Mean Change in Blood Eosinophil Count (Biomarker Population) 
  
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 133 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
 
Figure 
Figure 14.2.1.3 
Title 1 
Kaplan-Meier Curves for Time to 1-point Reduction in Total Polyp Score (TPS)  
Title 2  
MITT Population 
Type of graph 
Kaplan-Meier Step Function 
y-axis 
Survival Probability 
y-axis (label) 
Survival Probability 
x-axis 
Weeks  
x-axis (label) 
Survival Time (weeks) 
Legend 
AK001 25mg, Placebo 
Footnotes 
Note: Figure corresponds to Table 14.2.9.8 
 
path\t_program.sas date 
time   
Additional information 
 
Programming note: add a superimposed table on the right corner of the cuves, as follows --- 
 
Placebo 
AK001 25mg 
AK001 250 mg 
AK001 Combined 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
95% CI 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
p-value 
 
0.xxxx 
0.xxxx 
0.xxxx 
HR 
 
xx.x 
xx.x 
xx.x 
95% CI 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
p-value 
 
0.xxxx 
0.xxxx 
0.xxxx 
  
 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 134 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Allakos, Inc. 
 
Statistical Analysis Plan 
AK001-002 
 
16 August 2017 
 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 135 of 175 
CONFIDENTIAL 
 
 
 
 
 
 
 
 
Appendix K:  Listing Layouts 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 136 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.1.1.1 
Subject Populations 
 
Subject 
ID 
Treatment Group 
ITT 
Population [1] 
Safety 
Population [2] 
MITT 
Population [3] 
PP 
Population [4] 
Biomarker 
Population [5] 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
xxxxxx xxxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
xxxxxx xxxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
xxxxxx xxxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
xxxxxx xxxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 [1] All randomized subjects. 
[2] All randomized subjects who take at least one dose of study drug.  
[3] All randomized subjects who take at least one dose of the study drug and have both a baseline and at least one post-baseline efficacy assessment. 
[4] All MITT population subjects who have a week 12 visit and valid efficacy measurements.  
[5] All randomized subjects who has at least 1 sample obtained for biomarker analysis. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 137 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.1.1.2 
Subject Disposition 
 
Subject 
ID 
Treatment Group 
Completed 
Treatment 
Date of Last 
Dose 
Reason for 
Discontinuing 
Study Drug 
Completed 
Study 
Date of Study 
Completion / 
Discontinuation 
 
Reason(s) that Subject Did 
Not Complete the Study 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
Date 
Reason 
Yes/No 
date9. 
Reason* 
xxxxxx xxxxxxxxxx 
Yes/No 
Date 
Reason 
Yes/No 
date9. 
Reason {including Other 
description} 
xxxxxx xxxxxxxxxx 
Yes/No 
Date 
Reason 
Yes/No 
date9. 
Reason 
xxxxxx xxxxxxxxxx 
Yes/No 
Date 
Reason 
Yes/No 
date9. 
Reason 
xxxxxx xxxxxxxxxx 
Yes/No 
Date 
Reason 
Yes/No 
date9. 
Reason 
… 
 
 
 
 
 
 
 
 
 
 
 
 
Note: * indicates primary reason. 
  
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 138 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.1.1.3 
Subject Visit Dates 
 
Subject ID 
Treatment Group 
Visit 
Visit Date 
 
 
 
xxxxxx 
xxxxxxxxxx 
Screening 
date 
 
Baseline 
 
 
Day 0 
 
 
Week 2 
 
 
Week xx 
 
 
Week xx 
 
 
… 
 
 
Follow-up Visit 
 
 
Unscheduled 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID and visit date. 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 139 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.2.2 
Protocol Deviations 
 
 
Subject ID 
Treatment Group 
Protocol Deviation 
Category 
Protocol Deviation 
Type 
 
Deviation Date 
 
Deviation Time 
 
Action Taken 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
category 
type 
date9. 
time5. 
action 
xxxxxx 
xxxxxxxxxx 
category 
type 
date9. 
time5. 
action 
xxxxxx 
xxxxxxxxxx 
category 
type 
date9. 
time5. 
action 
xxxxxx 
xxxxxxxxxx 
category 
type 
date9. 
time5. 
action 
… 
 
 
 
 
 
 
 
 
 
 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
Programming note: Protocol Deviation Category includes Informed Consent, Randomization Error, Safety, Efficacy, IP/Treatment Deviation, and Other Protocol Deviations. 
Protocol deviation Type includes Informed Consent Procedures and etc which was described on CRF form.  


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 140 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.2.3 
Inclusion/Exclusion Findings 
 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID.
Subject 
ID 
 
Treatment Group 
Meet All Eligibility 
Criteria 
If Re-Screen, Initial 
Screening Number 
Criterion Type 
Criterion No. 
Protocol 
Version Date 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
xxxxxx 
Inclusion/Exclusion 
xx 
date9. 
xxxxxx 
xxxxxxxxxx 
Yes/No 
xxxxxx 
Inclusion/Exclusion 
xx 
date9. 
xxxxxx 
xxxxxxxxxx 
Yes/No 
xxxxxx 
Inclusion/Exclusion 
xx 
date9. 
xxxxxx 
xxxxxxxxxx 
Yes/No 
xxxxxx 
Inclusion/Exclusion 
xx 
date9. 
… 
 
 
 
 
 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 141 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.1.4.1 
Informed Consent 
 
 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID and informed consent date, in the event of multiple forms. 
Programming note: Date of the initial consent form will be reposted. 
 
 
Subject 
ID 
Treatment 
Group 
Date Signed Informed 
Consent 
Protocol Version Date at 
Initial Consent 
 
xxxxxx xxxxxxxxxx 
date9. 
xxxxxx 
 
… 
 
xxxxxx xxxxxxxxxx 
date9. 
xxxxxx 
 
… 
 
xxxxxx xxxxxxxxxx 
date9. 
xxxxxx 
 
… 
 
xxxxxx xxxxxxxxxx 
date9. 
xxxxxx 
 
… 
 
 
… 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 142 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.1.4.2 
Withdrawal of Consent 
 
 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID.  
 
 
Subject 
ID 
Treatment 
Group 
Withdrew Consent 
Study Participant 
Withdrew Date 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
xxxxxx 
date9. 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
xxxxxx 
date9. 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
xxxxxx 
date9. 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
xxxxxx 
date9. 
 
 
 
 
 
… 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 143 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.5.1 
Demographics and Baseline Characteristics 
Part 1 of 2 
 
Subject ID 
Treatment 
Group 
Region 
Age 
(years) [1] 
Gender 
Ethnicity 
Race 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Region 
xx 
Male/Female 
Ethnicity 
Race 
xxxxxx 
xxxxxxxxxx 
Region 
xx 
Male/Female 
Ethnicity 
Race 
xxxxxx 
xxxxxxxxxx 
Region 
xx 
Male/Female 
Ethnicity 
Race 
xxxxxx 
xxxxxxxxxx 
Region 
xx 
Male/Female 
Ethnicity 
Race 
… 
 
 
 
 
Race 
 
 
 
 
 
Race 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age on Consent Date. 
 
path\l_program.sas date 
time   
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 144 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 2 of x 
AK001-002 
Listing 16.2.4.5.2  
Demographics and Baseline Characteristics 
Part 2 of 2 
 
Subject ID 
Treatment 
Group 
Height 
(cm) 
Weight 
(kg) 
BMI 
(kg/m2) 
TPS Score 
Use of Asthma 
Rescue Therapy 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
xx 
xx 
xx.x 
xx.x 
Yes/No 
xxxxxx 
xxxxxxxxxx 
xx 
xx 
xx.x 
xx.x 
Yes/No 
xxxxxx 
xxxxxxxxxx 
xx 
xx 
xx.x 
xx.x 
Yes/No 
xxxxxx 
xxxxxxxxxx 
xx 
xx 
xx.x 
xx.x 
Yes/No 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 145 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 2 of x 
AK001-002 
Listing 16.2.4.6  
Relevant Respiratory Histroy at Screening 
 
Subject ID 
Treatment 
Group 
Have 
Asthma? 
If Yes, 
Onset Date 
Experienced 
Asthma 
Exacerbation? 
Had 
Rhinosinusitus 
Symptom? 
If Yes, Symptom 
 
Have Aspirin 
Sensitivity? 
If Yes, 
Diagnosis 
Date 
 
 
Ongoing? 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. 
Yes/No 
Yes/No 
Anterior nasal discharge 
Yes/No 
date9. 
Yes/No 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. 
Yes/No 
Yes/No 
Posterior nasal discharge 
Yes/No 
date9. 
Yes/No 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. 
Yes/No 
Yes/No 
Decreased sense of smell 
Yes/No 
date9. 
Yes/No 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. 
Yes/No 
Yes/No 
Facial pain or pressure 
Yes/No 
date9. 
Yes/No 
… 
 
 
 
 
 
Yes/No 
date9. 
Yes/No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 146 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.7 
Medical History at Screening 
 
Subject ID Treatment Group 
MedDRA System 
Organ Class 
Condition // MedDRA Preferred 
Term 
CRF Start/Stop Date 
Unknown 
Onset Date 
Ongoing/Resolved 
End Date  
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Body System 
Verbatim term // MedDRA 
Preferred Term 
Checkbox 
date9. 
Ongoing/Resolved 
date9. 
 
Body System 
Verbatim term // MedDRA 
Preferred Term 
value 
date9. 
Ongoing/Resolved 
date9. 
 
Body System 
Verbatim term // MedDRA 
Preferred Term 
 
date9. 
Ongoing/Resolved 
date9. 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Body System 
Verbatim term // MedDRA 
Preferred Term 
 
date9. 
Ongoing/Resolved 
date9. 
 
Body System 
Verbatim term // MedDRA 
Preferred Term 
 
date9. 
Ongoing/Resolved 
date9. 
 
Body System 
Verbatim term // MedDRA 
Preferred Term 
 
date9. 
Ongoing/Resolved 
date9. 
… 
 
 
 
 
 
 
 
 
 
 
 
 
path\l_program.sas date 
time   
 
Programming note: sort by subject ID and onset date within each subject. 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 147 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.8 
Physical and Neurological Examination 
 
Subject  
ID 
Treatment 
Group 
Target  
Visit 
Visit Date 
 (Study Day) 
Body System 
Overall Assessment 
Description of 
Abnormality 
Clinically Significant 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Screening 
date9. (xx) 
Body System 1 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 2 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 3 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
… 
 
 
 
 
Day 1 Pre-Dose 
date9. (xx) 
Body System 1 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 2 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 3 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
… 
 
 
 
 
Day 1 Post-Dose 
date9. (xx) 
Body System 1 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 2 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 3 
Normal/Abnormal 
Description 
Yes/No 
 
 
… 
 
… 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Screening 
date9. (xx) 
Body System 1 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 2 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 3 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
 
 
 
 
 
Day 1 Pre-Dose 
date9. (xx) 
Body System 1 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 2 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 3 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
 
 
 
 
 
Day 1 Post-Dose 
date9. (xx) 
Body System 1 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 2 
Normal/Abnormal 
Description 
Yes/No 
 
 
 
 
Body System 3 
Normal/Abnormal 
Description 
Yes/No 
 
 
… 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time   
  
Programming note: Sort by subject ID.  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 148 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.9 
Symptom Directed Physical Examination 
 
Subject ID 
Treatment 
Group 
 
Target Visit 
Performed? 
Exam Date 
(Study Day) 
 
Exam Time 
Infusion Site 
Reaction? 
New/Worsened 
CS findings? 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day 0 
Yes/No 
date9. (xx) 
time5. 
Yes/No 
Yes/No 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
Yes/No 
Yes/No 
 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
Yes/No 
Yes/No 
 
 
… 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day 0 
Yes/No 
date9. (xx) 
time5. 
Yes/No 
Yes/No 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
Yes/No 
Yes/No 
 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
Yes/No 
Yes/No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. CS=Clinically Significant 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 149 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.10 
Electrocardiogram at Screening 
 
Subject  
ID 
Treatment Group 
 
 
Performed?  
Assessment 
Date  
(Study Day) 
Assessment 
Time 
Heart 
Rate 
(bpm) 
PR 
Interval 
(ms) 
RR 
Interval 
(ms) 
QRS 
Interval 
(ms) 
QT 
Interval 
(ms) 
QTc Interval 
(Fridericia) 
(ms) 
QTc Interval 
(Bazett)  
(ms) 
Any Findings 
Abnormal?[1] 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Yes: CS/NCS / 
No/cant/Unable to 
evaluate 
 
 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
date9. (xx) 
time5.  
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. CS=Clinically Significant; NCS=Not Clinically Significant 
[1] Investigator interpretation of ECG and clinical significance 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 150 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.11.1 
Pregnancy Test 
 
Subject ID 
Treatment 
Group 
Visit 
Performed? 
If Yes, Type of 
Test 
Reason if not 
done 
Test Date (Study 
Day) 
 
Test Time 
Result 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Screening 
Yes/No 
Test 
Surgically sterile 
date9. (xx) 
time5. 
Negative/Positive 
 
Day -3 
Yes/No 
Test 
Post-menopausal 
date9. (xx) 
time5. 
Negative/Positive 
 
 
Week x 
Yes/No 
Test 
Other (Specify) 
date9. (xx) 
time5. 
Negative/Positive 
 
 
… 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
Test 
Surgically sterile 
date9. (xx) 
time5. 
Negative/Positive 
 
 
Day -3 
Yes/No 
Test 
Post-menopausal 
date9. (xx) 
time5. 
Negative/Positive 
 
 
Week x 
Yes/No 
Test 
Other (Specify) 
date9. (xx) 
time5. 
Negative/Positive 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID.


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 151 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.11.2 
Pregnancy Report during Study 
 
Subject ID 
Treatment 
Group 
Patient or patient’s 
partner became 
pregnant? 
Pregnancy Date 
(Study Day) 
 
Delivery 
Date 
Outcome 
 
Infant 
Weight (kg) 
 
Infant 
Height (cm) 
 
Any Congenital 
Abnormalities? 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. (xx) 
date9. 
Normal/Abnormal 
xx 
xx 
Yes/No 
 
Yes/No 
date9. (xx) 
date9. 
Normal/Abnormal 
xx 
xx 
Yes/No 
 
 
Yes/No 
date9. (xx) 
date9. 
Normal/Abnormal 
xx 
xx 
Yes/No 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. (xx) 
date9. 
Normal/Abnormal 
xx 
xx 
Yes/No 
 
 
Yes/No 
date9. (xx) 
date9. 
Normal/Abnormal 
xx 
xx 
Yes/No 
 
 
Yes/No 
date9. (xx) 
date9. 
Normal/Abnormal 
xx 
xx 
Yes/No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 152 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.12 
Follicle-Stimulating Hormone (FSH) Test at Screening 
 
Subject ID 
Treatment 
Group 
Performed? 
Collection Date 
(Study Day) 
Collection 
Time 
Result (IU/L) 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. (xx) 
time5. 
xx 
 
Yes/No 
date9. (xx) 
time5. 
xx 
 
 
Yes/No 
date9. (xx) 
time5. 
xx 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. (xx) 
time5. 
xx 
 
 
Yes/No 
date9. (xx) 
time5. 
xx 
 
 
Yes/No 
date9. (xx) 
time5. 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
Programming note:  
Repeat Listing 16.2.4.13 for Fecal Sample Test at Screening {Replace column “Result (IU/L) with “Result”, and display “Negative/Positive” in the result field} 
Repeat Listing 16.2.4.14 for Anti-Drug Antibody (ADA) {Add a column “Target Visit” after “Treatment Group”; Replace column “Result (IU/L) with “Result”}   
Repeat Listing 16.2.4.15 for Exploratory Biomarkers {Add a column “Target Visit” after “Treatment Group”; Replace column “Result (IU/L) with “Result”, display all collected  
biomarkers analysis results}   
Repeat Listing 16.2.4.16 for Serum Samples for Total Immunoglobulin E and ImmunoCAP on Day -3 {Add a column “Typet” after “Treatment Group”; Replace column “Result 
(IU/L) with “Result”}   
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 153 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 154 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.17 
Prior Medications 
 
Subject  
ID 
Treatment 
Group 
CM 
# 
Verbatim Term // 
Generic Name 
Start Date 
(Study Day) 
Stop Date 
(Study Day) 
Dose 
Units 
Dose Form 
Route 
Frequency 
Indication 
Primary 
Reason for 
Medication 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
1 
Verbatim Term // 
Generic Name 
date9. (xx) 
date9. (xx) 
dose 
unit 
dose form 
route 
frequency 
indication 
xxxx 
 
2 
Verbatim Term // 
Generic Name 
date9. (xx) 
date9. (xx) 
dose 
unit 
dose form 
route 
frequency 
indication 
xxxx 
 
3 
Verbatim Term // 
Generic Name 
date9. (xx) 
date9. (xx) 
dose 
unit 
dose form 
route 
frequency 
indication 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
1 
Verbatim Term // 
Generic Name 
date9. (xx) 
date9. (xx) 
dose 
unit 
dose form 
route 
frequency 
indication 
xxxx 
 
2 
Verbatim Term // 
Generic Name 
date9. (xx) 
date9. (xx) 
dose 
unit 
dose form 
route 
frequency 
indication 
xxxx 
 
3 
Verbatim Term // 
Generic Name 
date9. (xx) 
date9. (xx) 
dose 
unit 
dose form 
route 
frequency 
indication 
xxxx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. Prior Medications are those started within the 30 days before Screening.  
 
path\l_program.sas date 
time   
 
Programming note: sort by subject ID and start date and stop date within each subject. 
 
Programming note: Repeat listing 16.2.4.18 for  Concomitant Medications {Replace prior footnote with “Concomitant medications are those medications taken at the start of 
study drug or initiated after the initial dose of study drug.” Add a flag # for medication that start after the last dose of study drug.}  
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 155 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.4.19 
Intranasal Steroid Adjustment at Day 0 
 
Subject ID 
Treatment 
Group 
Completed 
Run-in? 
Start Date 
(Study Day)   
End Date 
(Study Day) 
 
Compliance (%) 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. (xx) 
date9. (xx) 
xx.x 
 
Yes/No 
date9. (xx) 
date9. (xx) 
xx.x 
 
 
Yes/No 
date9. (xx) 
date9. (xx) 
xx.x 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Yes/No 
date9. (xx) 
date9. (xx) 
xx.x 
 
 
Yes/No 
date9. (xx) 
date9. (xx) 
xx.x 
 
 
Yes/No 
date9. (xx) 
date9. (xx) 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 156 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.5.20 
Study Drug Administration 
 
Subject ID 
Treatment 
Group 
Target 
Visit 
Drug 
Administered? 
Arm for 
Administration Start Date  
 
Start Time 
 
End Time 
Full Infusion 
Given? 
If Yes, Total 
Volume (mL) 
If No, Amount 
Given 
Infusion 
Interrupted? 
If Yes, 
Reason 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Day 0 
Yes/No 
Left/Right 
date9. (xx) 
time5. 
time5. 
Yes/No 
xx 
xx 
Yes (#)/No 
Reason 
 
Week 3 
Yes/No 
Left/Right 
date9. (xx) 
time5. 
time5. 
Yes/No 
xx 
xx 
Yes (#)/No 
Reason 
 
 
Week 7 
Yes/No 
Left/Right 
date9. (xx) 
time5. 
time5. 
Yes/No 
xx 
xx 
Yes (#)/No 
Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Day 0 
Yes/No 
Left/Right 
date9. (xx) 
time5. 
time5. 
Yes/No 
xx 
xx 
Yes (#)/No 
Reason 
 
 
Week 3 
Yes/No 
Left/Right 
date9. (xx) 
time5. 
time5. 
Yes/No 
xx 
xx 
Yes (#)/No 
Reason 
 
 
Week 7 
Yes/No 
Left/Right 
date9. (xx) 
time5. 
time5. 
Yes/No 
xx 
xx 
Yes (#)/No 
Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: # is the number of times interrupted 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Allakos, Inc. 
Page 1 of x 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 157 of 175 
CONFIDENTIAL 
 
 
AK001-002 
Listing 16.2.6.21.1 
Total Polyp Score (TPS) 
 
Subject ID 
Treatment 
Group 
Target Visit Performed? 
Date Performed 
(Study Day) 
Time 
Total Score 
 
 
 
 
xxxxxx xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
x 
 
Baseline 
Yes/No 
date9. (xx) 
time5. 
x 
 
Week X 
… 
Yes/No 
date9. (xx) 
 
time5. 
 
x 
 
 
 
 
 
xxxxxx xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
x 
 
Baseline 
Yes/No 
date9. (xx) 
time5. 
x 
 
Week X 
… 
Yes/No 
date9. (xx) 
 
time5. 
 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time 
 
Programming note: Sort by subject ID. 
 
Programming note: Repeat listing for the listings listed below 
Listing 16.2.6.21.2 
Size of Polyps (Lund-Mackay Score) {Add a column for “Lund-Mackay Scoring System” before 
“Total Score”}  
Listing 16.2.6.21.3 
Peak Nasal Inspiratory Flow (PNIF) {Replace column “Total Score” with columns “Reading 1 
(L/min)”, “Reading 2 (L/min)”, “Reading 3 (L/min)”, “Highest Reading (L/min)”} 
Listing 16.2.6.21.4 
University of Pennsylvania Smell Identification Test (UPSIT) 
Listing 16.2.6.21.5 
Sino-nasal Outcome Test-22 (SNOT-22) {Add a column for “Five Most Important Items” before 
“Total Score”, display items in the field} 
Listing 16.2.6.21.6 
Visual Analogue Scale (VAS) {Add two columns for “Symptom” and “Severity”}  
Listing 16.2.6.21.7 
Clinical Symptoms Improvement Scale 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 158 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.6.21.8.1 
36-Item Short Form Health Survey (SF-36) 
Part 1 of 3 
 
Subject ID 
Treatment 
Group 
Target 
Visit Performed? 
Date 
Performed 
(Study Day) 
Time 
GH1 
HT 
PF01 PF02 PF03 PF04 PF05 PF06 PF07 PF08 PF09 PF10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Day 0 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Day 0 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Day 0 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Day 0 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time 
 
Programming note: Sort by subject ID. 
Programming note: provide a key cover sheet for all the columns. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 159 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.6.21.8.2 
36-Item Short Form Health Survey (SF-36) 
Part 2 of 3 
 
Subject 
ID 
Treatment 
Group 
Target 
Visit 
RP1 
RP2 RP3 RP4 
RE1 
RE2 
RE3 
SF1 
BP1 BP2 VT1 MH1 MH2 MH3 VT2 MH4 VT3 MH5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
path\l_program.sas date 
time 
 
Programming note: Sort by subject ID. 
Programming note: provide a key cover sheet for all the columns. 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 160 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.6.21.8.3 
36-Item Short Form Health Survey (SF-36) 
Part 3 of 3 
 
Subject ID 
Treatment Group Target Visit 
VT4 
SF2 
GH2 GH3 GH4 GH5 
Total Score  
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
xx 
 
Week 3 
x 
x 
x 
x 
x 
x 
xx 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
xx 
 
Week 3 
x 
x 
x 
x 
x 
x 
xx 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
xx 
 
Week 3 
x 
x 
x 
x 
x 
x 
xx 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day 0 
x 
x 
x 
x 
x 
x 
xx 
 
Week 3 
x 
x 
x 
x 
x 
x 
xx 
 
… 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
path\l_program.sas date 
time 
 
Programming note: Sort by subject ID. 
Programming note: provide a key cover sheet for all the columns. 
 
Programming note: Repeat listing for the listing listed below--- 
Listing 16.2.6.21.9 
Asthma Control Test (ACT) {Replace item name columns with columns “ACT1”, “ACT2”, “ACT3”, 
“ACT4”, and “ACT5”}  
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 161 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.6.21.10 
Spirometry Test 
 
Subject ID 
Treatment 
Group 
Target Visit 
 
Performed? 
Date Performed 
(Study Day) 
Time 
FEV1(%) 
 
FVC(%) 
 
FEF(%) 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xx 
xx 
xx 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
xx 
xx 
xx 
 
Week 7 
Yes/No 
date9. (xx) 
 
time5. 
 
xx 
xx 
xx 
xxxxxx xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xx 
xx 
xx 
 
Week 3 
Yes/No 
date9. (xx) 
time5. 
xx 
xx 
xx 
 
Week 7 
Yes/No 
date9. (xx) 
 
time5. 
 
xx 
xx 
xx 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. FEV1=Forced Expiratory Volume in 1 Second; FVC=Forced Vital Capacity; FEF=Forced 
Expiratory Flow 
 
path\l_program.sas date 
time 
 
Programming note: Sort by subject ID. 
 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 162 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.6.21.11.1 
Sub-study Biomarkers 
Part 1 of 2 
 
Subject ID 
Treatment 
Group 
Target 
Visit 
Collection Date 
(Study Day) 
Collection 
Time 
ECP 
Histamin Tryptase Prostaglandins Leukotrienes Chymase 
Carboxypeptidase 
A3 
 
Cytokines 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 163 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.6.21.11.2 
Sub-study Biomarkers 
Part 2 of 2 
 
Subject ID 
Treatment 
Group 
Target 
Visit 
Collection Date 
(Study Day) 
Collection 
Time 
IL-5 
IL-17 
IFN 
IL-4 
IL-13 
TSLP 
 
IL-33 
 
IL-8 
 
TNF 
 
Albumin 
 
MPO 
Growth 
Factors 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Day -3 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Week 2 
date9. (xx) 
time5. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time 
 
Programming note: Sort by subject ID. Listing will include all the biomarkers from biomarker analysis. 
Programming note: Please be sure all biomarkers are listed. The column headings need to be inserted based on the actual data to be received. 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 164 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.7.22.1 
Adverse Events 
 
Subject  
ID 
Treatment 
Group 
AE 
# 
Verbatim Term // 
Preferred Term 
Start 
Date/Time[1] 
(Study Day) 
End  
Date/Time[1] 
(Study Day) 
Start after last 
visit? 
If Yes, Visit Date? Serious 
Severity 
Relationship 
to Study Drug 
Action Taken  
with Study Drug 
Other 
Action 
Outcome 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 1 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
Yes/Date9. 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
2 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
No/-- 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
3 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
Yes/Date9. 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 1 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
No/-- 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
2 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
Yes/Date9. 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
3 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
No/-- 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 1 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
Yes/Date9. 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
2 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
No/-- 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
3 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
Yes/Date9. 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 1 Verbatim Term // 
Preferred Term 
date9./time/5. 
(xx) 
date9./time5. 
(xx) 
No/-- 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
2 Verbatim Term // 
Preferred Term 
date9./time5. 
(xx) 
date9./time5. 
(xx) 
Yes/Date9. 
Yes/No 
severity 
relationship 
action 
action 
outcome 
 
 
3 Verbatim Term // 
Preferred Term 
date9./time/5. 
(xx) 
date9./time5. 
(xx) 
No/-- 
Yes/No 
severity 
relationship 
action 
action 
outcome 
… 
 
 
 
 
 
 
 
 
 
 
 
 
* Pre-treatment adverse event  
# Post-treatment adverse event 
[1] If time is marked unknown fill the time with “Unk”, otherwise with “--” 
Note: Study day is calculated as days since the date of first dose of study drug. 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 165 of 175 
CONFIDENTIAL 
 
 
path\l_program.sas date 
time   
Programming note: sort by subject ID and onset date and resolution date within each subject.  Please ensure ALL data from AE CRF appear in listing. 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 166 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.7.22.2 
Treatment-Emergent Serious Adverse Events (Collected on AE CRF) 
 
Subject  
ID 
Treatment 
Group 
AE 
# 
Verbatim Term // 
Preferred Term 
Start Date 
(Study Day) 
 
Start 
Time 
End Date 
(Study Day) 
 
End 
Time 
Severity 
Relationship 
to Study Drug 
Action Taken  
with Study 
Drug 
Other 
Action 
Outcome 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
1 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
2 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
3 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
1 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
2 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
3 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
1 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
2 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
3 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
1 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
2 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
3 
Verbatim Term // 
Preferred Term 
date9. (xx) 
time5. 
date9. (xx) 
time5. 
severity 
relationship 
action 
action 
outcome 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is calculated as days since the date of first dose of study drug. 
path\l_program.sas date 
time   
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 167 of 175 
CONFIDENTIAL 
 
 
Programming note: sort by subject ID and onset date and resolution date within each subject.  
Programming note: Repeat listing for the following: 
Listing 16.2.7.22.3    Fatal Treatment-Emergent Serious Adverse Events (Collected on AE CRF) 
Listing 16.2.7.22.4    Non-Fatal Treatment-Emergent Serious Adverse Events (Collected on AE CRF) 
 
 
 
 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 168 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.8.23.1.1 
Central Laboratory Normal Ranges – Conventional Units 
 
 
Conventional Units 
 
System International Units 
 
Panel Name 
Laboratory Test 
Normal Range 
Unit 
 
Normal Range 
Unit 
Effective Date 
 
 
 
 
 
 
 
Hematology 
WBC 
min-max 
unit. 
 
min-max 
unit. 
date9. 
Hematocrit 
min-max 
unit. 
 
min-max 
unit. 
date9. 
Hemoglobin 
min-max 
unit. 
 
min-max 
unit. 
date9. 
… 
 
 
 
 
 
 
Serum Chemistry 
AST 
min-max 
unit. 
 
min-max 
unit. 
date9. 
… 
 
 
 
 
 
 
Urinalysis 
pH 
min-max 
unit. 
 
min-max 
unit. 
date9. 
… 
 
 
 
 
 
 
path\l_program.sas date 
time   
 
Programming note: listing will include all the laboratory tests with normal ranges in central lab data.  Repeat for Listing 16.2.8.23.1.2 using SI Units 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 169 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
 
AK001-002 
Listing 16.2.8.23.2.1 
Hematology – Conventional Units 
Part 1 of 2 
 
Subject  
ID 
Treatment 
Group 
Target 
Visit 
Performed? 
Collection 
Date  
(Study Day) 
Collection 
Time 
WBC 
(109 /L) 
Neutrophils 
(%) 
Neutrophils 
(109 /L) 
Lymphocytes 
(%) 
Lymphocytes 
(109 /L) 
Monocytes 
(%) 
Monocytes 
(109 /L) 
Eosinophils 
(%) 
Eosinophils 
(109 /L) 
Basophils 
(%) 
Basophils 
(109 /L) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note; L=Low, H=High;*=Potentially Clinically Significant; #=Abnormal/Clinically Significant per Investigator. Study day is calculated as days since the date of first dose of study 
drug. 
 
path\l_program.sas date 
time   
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 170 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 2 of x 
AK001-002 
Listing 16.2.8.23.2.2 
Hematology – Conventional Units 
Part 2 of 2 
 
Subject  
ID 
Treatment 
Group 
Target 
Visit 
Collection 
Date 
(Study Day) 
Collection 
Time 
Platelets 
 (109 /L) 
RBC 
(1012 /L) 
Hemoglobin 
(mg/dL) 
Hematocrit 
(%) 
Reticulocytes 
(109 /L) 
Reticulocytes 
(%) 
MCV 
(fL) 
 
Heinz Bodies 
(109 /L) 
 
MCH 
(pg) 
 
MCHC 
(g/dL) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Screening date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
Day -3 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
Week 2 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Screening date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
Day -3 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
Week 2 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Screening date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
Day -3 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
Week 2 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx 
Screening date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
 
Day -3 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
 
Week 2 
date9. (xx) 
time5. 
xxx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xxx 
xx.x 
xx.x 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: L=Low, H=High;*=Potentially Clinically Significant; #=Abnormal/Clinically Significant per Investigator. Study day is calculated as days since the date of first dose of study 
drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. Listing will include all the laboratory tests from central lab data in Hematology, and conventional units will be displayed.  
Repeat for Listing 16.2.8.23.2.3 using SI Units 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 171 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.8.23.3.1 
Serum Chemistry – Conventional Units 
Part 1 of 2 
 
Subject 
ID 
Treatment 
Group 
Target Visit Performed? 
Collection 
Date (Study 
Day) 
Collection 
Time 
ALT 
(SGPT) 
(U/L) 
AST 
(SGOT) 
(U/L) 
Alkaline 
Phosphatase 
(U/L) 
GGT 
(U/L) 
Albumin 
(g/dL) 
Total 
Bilirubin 
(mg/dL) 
Direct 
Bilirubin 
(mg/dL) 
BUN  
(mg/dL) 
Creatinine 
(mg/dL) 
Creatine 
Kinase 
(U/L) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
xxx 
xxx 
xxx 
xxx 
x.x 
x.x 
x.x 
xx 
x.x 
x.x 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: L=Low, H=High;*=Potentially Clinically Significant; #=Abnormal/Clinically Significant per Investigator. Study day is calculated as days since the date of first dose of study 
drug.  
 
path\l_program.sas date 
time   
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 172 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 2 of x 
AK001-002 
Listing 16.2.8.23.3.2 
Serum Chemistry – Conventional Units 
Part 2 of 2 
 
Subject  
ID 
Treatment Group 
Target Visit 
Collection 
Date (Study 
Day) 
Collection 
Time 
Sodium 
(mEq/L) 
Potassium 
(mEq/L) 
Chloride 
(mEq/L) 
Bicarbonate 
(mEq/L) 
Glucose 
(mg/dL) 
 Lactate 
Dehydrogenase 
(IU/L) 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Screening 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
Day -3 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
Week 2 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
… 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Screening 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
Day -3 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
Week 2 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
… 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Screening 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
Day -3 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
Week 2 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
… 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Screening 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
Day 1 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
 
Week 2 
date9. (xx) 
time5. 
xxx 
x.x 
xxx 
xx 
xxx 
xx.x 
 
 
… 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: L=Low, H=High;*=Potentially Clinically Significant; #=Abnormal/Clinically Significant per Investigator. Study day is calculated as days since the date of first dose of study 
drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. Listing will include all the laboratory tests from central lab data in Serum Chemistry, and conventional units will be displayed.  
Repeat for Listing 16.2.8.23.3.3 using SI Units 
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 173 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.8.23.4 
Urinalysis  
 
Subject 
ID 
Treatment 
Group 
Target 
Visit 
 
 
Performed? 
Collection 
Date (Study 
Day) 
Collection 
Time 
Specific 
Gravity 
Color Protein pH Blood Glucose Ketones 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
… 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
… 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
… 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx Screening
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Day -3 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
Week 2 
Yes/No 
date9. (xx) 
time5. 
result 
result 
result result result 
result 
result 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: L=Low, H=High;*=Potentially Clinically Significant; #=Abnormal/Clinically Significant per Investigator. Study day is calculated as days since the date of first dose of study 
drug.  
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. Listing will include all the laboratory tests from central lab data in Urinalysis. 
Programming note: Please be sure all lab parameters are listed. The column headings need to be inserted based on the actual data to be received. 
 
  
 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 174 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.8.24.1 
Vital Signs 
 
Subject 
ID 
Treatment 
Group 
Target  
Visit 
Performed? 
Date of 
Measurement 
(Study Day) 
Start Time 
Supine Position 
 
Time of 
Measurement 
Height 
(cm) 
Weight 
(kg) 
Temperature 
(°C) 
Respiration 
Rate 
(breaths/min) 
Systolic 
Blood Pressure 
(mmHg) 
Diastolic 
Blood Pressure 
(mmHg) 
Pulse Rate 
(beats/min) 
Any Findings 
Abnormal? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Screening 
Yes/No 
date9. (xx) 
time5. 
time5. 
xx.x. 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
Day -3 
 
date9. (xx) 
time5. 
time5. 
 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
Day 0 Pre-
dose 
 
date9. (xx) 
time5. 
time5. 
 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Screening 
 
date9. (xx) 
time5. 
time5. 
xx.x. 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
Day -3 
 
date9. (xx) 
time5. 
time5. 
 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
Day 0 Pre-
dose 
 
date9. (xx) 
time5. 
time5. 
 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx xxxxxxxxxx Screening 
 
date9. (xx) 
time5. 
time5. 
xx.x. 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
Day 1 Pre-
Dose 
 
date9. (xx) 
time5. 
time5. 
 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
 
Week 2 
 
date9. (xx) 
time5. 
time5. 
 
xxx.x 
xx.x 
xx 
xxx 
xxx 
xx 
Yes: CS/NCS / 
No 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CS= Clinically Significant; NCS = Not Clinically Significant; *=Potentially Clinically Significant.  On Days 0, 21 and 49, vital signs will be measured pre-dose, every 15 
minutes after the start of infusion, and immediately following the end of infusion.  Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID. 
 


 
 
ak001-002_statistical analysis plan_final_v1_2017_08_16 
 
Page 175 of 175 
CONFIDENTIAL 
 
 
Allakos, Inc. 
Page 1 of x 
AK001-002 
Listing 16.2.8.24.2 
Vital Sign Results of Potential Clinical Significance 
 
Subject ID 
Treatment Group 
Parameter (unit) 
Criteria 
Target  
Visit 
Collection Date 
(Study Day) 
Collection Time 
Results 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Temperature (°C) 
criteria 
Week x 
date9. (xx) 
time5. 
result 
 
 
 
 
 
 
 
 
 
Systolic Blood 
Pressure (mmHg) 
criteria 
Week x 
date9. (xx) 
time5. 
result 
 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Temperature (°C) 
criteria 
Week x 
date9. (xx) 
time5. 
result 
 
 
 
 
 
 
 
Systolic Blood 
Pressure (mmHg) 
criteria 
Week x 
date9. (xx) 
time5. 
result 
 
 
 
 
 
 
xxxxxx 
xxxxxxxxxx 
Temperature (°C) 
criteria 
Week x 
date9. (xx) 
time5. 
result 
 
 
 
 
 
 
 
Systolic Blood 
Pressure (mmHg) 
criteria 
Week x 
date9. (xx) 
time5. 
result 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CS= Clinically Significant; NCS = Not Clinically Significant. Study day is calculated as days since the date of first dose of study drug. 
 
path\l_program.sas date 
time   
 
Programming note: Sort by subject ID.