Open-Label Extension Study of Omalizumab in Patients With Chronic Rhinosinusitis With Nasal Polyps
Phase: PHASE3
Conditions: Nasal Polyps, Chronic Rhinosinusitis
Sponsor: Hoffmann-La Roche

 
Official Title: Open-Label Extension Study of Omalizumab in Patients With Chronic 
Rhinosinusitis With Nasal Polyps 
NCT Number: NCT03478930 
Document Date: Protocol Version 1: 16-October-2017 
 
 
 

FINAL PROTOCOL APPROVAL
CONFIDENTIAL
This clinical study is being sponsored globally by F. Hoffmann-La Roche Ltd of Basel, 
Switzerland. However, it may be implemented in individual countries by Roche's local affiliates, 
including Genentech, Inc. in the United States.  The information contained in this document, especially 
any unpublished data, is the property of F. Hoffmann-La Roche Ltd (or under its control) and therefore 
is provided to you in confidence as an investigator, potential investigator, or consultant, for review by 
you, your staff, and an applicable Ethics Committee or Institutional Review Board.  It is understood that 
this information will not be disclosed to others without written authorization from Roche except to the 
extent necessary to obtain informed consent from persons to whom the drug may be administered.
Omalizumab—F. Hoffmann-La Roche Ltd
1/Protocol WA40169, Version 1
PROTOCOL
TITLE:
OPEN-LABEL EXTENSION STUDY OF 
OMALIZUMAB IN PATIENTS WITH CHRONIC 
RHINOSINUSITIS WITH NASAL POLYPS
PROTOCOL NUMBER:
WA40169
VERSION NUMBER:
1
EUDRACT NUMBER:
2017-003450-16
IND NUMBER:
5369
TEST PRODUCT:
Omalizumab (IGE025)
MEDICAL MONITOR:
, M.D.
SPONSOR:
F. Hoffmann-La Roche Ltd
DATE FINAL:
See electronic date stamp below
 
16-Oct-2017 13:50:39
Title
Approver's Name
Company Signatory
Date and Time (UTC)

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TABLE OF CONTENTS
PROTOCOL ACCEPTANCE FORM .................................................................... 9
PROTOCOL SYNOPSIS .................................................................................... 10
1.
BACKGROUND .......................................................................................... 18
1.1
Background on Chronic Rhinosinusitis with Nasal 
Polyps.................................................................................... 18
1.2
Background on Omalizumab ................................................. 19
1.3
Study Rationale and BenefitRisk Assessment..................... 19
1.3.1
BenefitRisk Assessment...................................................... 19
2.
OBJECTIVES AND ENDPOINTS ............................................................... 21
3.
STUDY DESIGN......................................................................................... 24
3.1
Description of the Study......................................................... 24
3.2
End of Study and Length of Study......................................... 26
3.3
Rationale for Study Design.................................................... 26
3.3.1
Rationale for Omalizumab Dose and Schedule..................... 26
3.3.2
Rationale for Open-Label Study Design ................................ 27
4.
MATERIALS AND METHODS .................................................................... 27
4.1
Patients.................................................................................. 27
4.1.1
Inclusion Criteria.................................................................... 27
4.1.2
Exclusion Criteria................................................................... 28
4.1.3
Omalizumab Dose Determination.......................................... 28
4.2
Method of Treatment Assignment and Blinding..................... 28
4.3
Study Treatment and Other Treatments Relevant 
to the Study Design ............................................................... 28
4.3.1
Study Treatment Formulation, Packaging, and 
Handling ................................................................................ 29
4.3.1.1
Omalizumab .......................................................................... 29
4.3.1.2
Mometasone Furoate Monohydrate Nasal Spray .................. 29
4.3.2
Study Treatment Dosage, Administration, and 
Compliance............................................................................ 29
4.3.3
Mometasone Furoate Monohydrate Nasal Spray .................. 30
4.3.4
Investigational Medicinal Product Accountability ................... 30

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4.3.5
Continued Access to Omalizumab......................................... 31
4.4
Concomitant Therapy ............................................................ 31
4.4.1
Prohibited Therapy ................................................................ 31
4.5
Study Assessments ............................................................... 32
4.5.1
Informed Consent Forms and Screening Log........................ 32
4.5.2
Physical Examinations........................................................... 32
4.5.3
Vital Signs.............................................................................. 33
4.5.4
CRSwNP Specific Assessments............................................ 33
4.5.5
Physician Review of eDiary Data and 
Compliance............................................................................ 33
4.5.6
Laboratory, Biomarker, and Other Biological 
Samples................................................................................. 33
4.5.7
Patient-Reported Outcomes .................................................. 34
4.5.7.1
Nasal Symptoms, including Nasal Congestion 
Score ..................................................................................... 35
4.5.7.2
Sino-Nasal Outcome Test-22 ................................................ 35
4.5.7.3
Patient Global Impression of Change.................................... 35
4.5.7.4
University of Pennsylvania Smell Identification 
Test........................................................................................ 35
4.5.7.5
Asthma Quality of Life Questionnaire (Patients 
with Comorbid Asthma Only)................................................. 35
4.5.7.6
EuroQol 5-Dimension 5-Level Questionnaire ........................ 36
4.5.7.7
Medical Outcomes Study Sleep Scale................................... 36
4.5.7.8
Healthy Days Core Module.................................................... 36
4.5.8
Optional Samples for Research Biosample 
Repository ............................................................................. 36
4.5.8.1
Overview of the Research Biosample Repository.................. 36
4.5.8.2
Approval by the Institutional Review Board or 
Ethics Committee .................................................................. 37
4.5.8.3
Sample Collection.................................................................. 37
4.5.8.4
Confidentiality........................................................................ 37
4.5.8.5
Consent to Participate in the Research 
Biosample Repository............................................................ 38
4.5.8.6
Withdrawal from the Research Biosample 
Repository ............................................................................. 38
4.5.8.7
Monitoring and Oversight....................................................... 39

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4.6
Treatment, Patient, Study, and Site 
Discontinuation...................................................................... 39
4.6.1
Study Treatment Discontinuation........................................... 39
4.6.2
Patient Discontinuation from Study........................................ 39
4.6.3
Study Discontinuation............................................................ 40
4.6.4
Site Discontinuation............................................................... 40
5.
ASSESSMENT OF SAFETY....................................................................... 40
5.1
Safety Plan ............................................................................ 41
5.1.1
Safety and Data Monitoring ................................................... 41
5.1.2
Anaphylaxis Adjudication Committee .................................... 41
5.1.3
Risks Associated with Omalizumab....................................... 41
5.1.3.1
Anaphylaxis ........................................................................... 41
5.1.3.2
Serum Sickness..................................................................... 42
5.1.3.3
Churg-Strauss Syndrome and Hypereosinophilic 
Syndrome .............................................................................. 43
5.1.3.4
Thrombocytopenia................................................................. 43
5.1.3.5
Malignancies.......................................................................... 43
5.1.3.6
Arterial Thrombotic Events .................................................... 44
5.1.3.7
Antibody Formation to Omalizumab ...................................... 44
5.1.4
Management of Patients Who Experience 
Specific Adverse Events........................................................ 44
5.1.4.1
Dose Modifications and Treatment Interruption..................... 44
5.1.4.2
Management of Drug Induced Liver Injuries.......................... 44
5.2
Safety Parameters and Definitions ........................................ 44
5.2.1
Adverse Events ..................................................................... 45
5.2.2
Serious Adverse Events (Immediately Reportable 
to the Sponsor)...................................................................... 45
5.2.3
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor).................................................... 46
5.3
Methods and Timing for Capturing and 
Assessing Safety Parameters................................................ 47
5.3.1
Adverse Event Reporting Period ........................................... 47
5.3.2
Eliciting Adverse Event Information....................................... 47
5.3.3
Assessment of Severity of Adverse Events ........................... 47

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5.3.4
Assessment of Causality of Adverse Events ......................... 48
5.3.5
Procedures for Recording Adverse Events............................ 48
5.3.5.1
Injection-Site Reactions......................................................... 49
5.3.5.2
Anaphylactic Reactions ......................................................... 49
5.3.5.3
Diagnosis versus Signs and Symptoms................................. 49
5.3.5.4
Adverse Events That Are Secondary to Other 
Events.................................................................................... 49
5.3.5.5
Persistent or Recurrent Adverse Events................................ 50
5.3.5.6
Abnormal Laboratory Values ................................................. 50
5.3.5.7
Abnormal Vital Sign Values ................................................... 51
5.3.5.8
Abnormal Liver Function Tests.............................................. 51
5.3.5.9
Deaths ................................................................................... 52
5.3.5.10
Preexisting Medical Conditions.............................................. 52
5.3.5.11
Lack of Efficacy or Worsening of Nasal Polyposis................. 52
5.3.5.12
Hospitalization or Prolonged Hospitalization.......................... 52
5.3.5.13
Adverse Events Associated with an Overdose or 
Error in Drug Administration .................................................. 53
5.3.5.14
Patient-Reported Outcome Data ........................................... 53
5.4
Immediate Reporting Requirements from 
Investigator to Sponsor.......................................................... 53
5.4.1
Emergency Medical Contacts................................................ 54
5.4.2
Reporting Requirements for Serious Adverse 
Events and Adverse Events of Special Interest..................... 55
5.4.2.1
Events That Occur prior to Study Drug Initiation.................... 55
5.4.2.2
Events That Occur after Study Drug Initiation........................ 55
5.4.3
Reporting Requirements for Pregnancies.............................. 55
5.4.3.1
Pregnancies in Female Patients............................................ 55
5.4.3.2
Abortions ............................................................................... 56
5.4.3.3
Congenital Anomalies/Birth Defects ...................................... 56
5.5
Follow-Up of Patients after Adverse Events .......................... 56
5.5.1
Investigator Follow-Up........................................................... 56
5.5.2
Sponsor Follow-Up ................................................................ 56
5.6
Adverse Events That Occur after the Adverse 
Event Reporting Period.......................................................... 56

 
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5.7 
Expedited Reporting to Health Authorities, 
Investigators, Institutional Review Boards, and 
Ethics Committees ................................................................. 57 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN ....................... 57 
6.1 
Determination of Sample Size ............................................... 57 
6.2 
Analysis Cohorts .................................................................... 58 
6.3 
Summaries of Treatment Group and Cohort 
Comparability ......................................................................... 58 
6.4 
Summaries of Conduct of Study ............................................ 59 
6.5 
Efficacy Analyses .................................................................. 59 
6.5.1 
Efficacy Analysis Populations ................................................ 59 
6.5.2 
Primary Efficacy Endpoints .................................................... 59 
6.5.2.1 
Nasal Polyp Score ................................................................. 60 
6.5.2.2 
Nasal Congestion Score ........................................................ 60 
6.5.3 
Secondary Efficacy Endpoints ............................................... 61 
6.5.3.1 
Nasal Polyp Score and Nasal Congestion Score ................... 61 
6.5.3.2 
Nasal Symptoms ................................................................... 61 
6.5.3.3 
SNOT-22, UPSIT, EQ-5D-5L, and AQLQ .............................. 62 
6.5.4 
Exploratory Efficacy/Psychometric Endpoints ........................ 62 
6.6 
Safety Analyses ..................................................................... 62 
6.6.1 
Primary Safety Analysis: Adverse Events .............................. 62 
6.6.2 
Secondary Safety Analysis: Clinical Laboratory 
Evaluations ............................................................................ 62 
6.7 
Pharmacokinetic/Pharmacodynamic Analyses ...................... 63 
6.8 
Interim Analysis ..................................................................... 63 
6.9 
Missing Data .......................................................................... 63 
6.10 
Unused and Spurious Data .................................................... 63 
7. 
DATA COLLECTION AND MANAGEMENT ............................................... 64 
7.1 
Data Quality Assurance ......................................................... 64 
7.2 
Electronic Case Report Forms ............................................... 64 
7.3 
Electronic Patient-Reported Outcome ................................... 65 
7.4 
Source Data Documentation .................................................. 65 
7.5 
Use of Computerized Systems .............................................. 66 
7.6 
Retention of Records ............................................................. 66 

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8.
ETHICAL CONSIDERATIONS.................................................................... 66
8.1
Compliance with Laws and Regulations ................................ 66
8.2
Informed Consent.................................................................. 67
8.3
Institutional Review Board or Ethics Committee.................... 68
8.4
Confidentiality........................................................................ 68
8.5
Financial Disclosure .............................................................. 69
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ..................................................................................... 69
9.1
Study Documentation ............................................................ 69
9.2
Protocol Deviations................................................................ 69
9.3
Site Inspections ..................................................................... 69
9.4
Administrative Structure......................................................... 70
9.5
Publication of Data and Protection of Trade 
Secrets .................................................................................. 70
9.6
Protocol Amendments ........................................................... 71
10. REFERENCES ........................................................................................... 72
LIST OF TABLES
Table 1
Objectives and Corresponding Endpoints................................... 21
Table 2
Adverse Event Severity Grading Scale ....................................... 47
Table 3
Causal Attribution Guidance ....................................................... 48
LIST OF FIGURES
Figure 1
Study Schema............................................................................. 26
LIST OF APPENDICES
Appendix 1 Schedule of Activities....................................................................... 77
Appendix 2 Omalizumab Dosing Table for Nasal Polyps ................................... 80
Appendix 3 Nasal Polyps Scoring System.......................................................... 81
Appendix 4 Nasal Symptoms Assessed Daily via Electronic Diary..................... 82
Appendix 5 Nasal Symptoms Assessed via In-Clinic or Telephone Interview .... 83
Appendix 6 Sino-Nasal Outcome Test-22 (SNOT-22) Questionnaire................. 84
Appendix 7 Patient Global Impression of Change .............................................. 85

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Appendix 8 Asthma Quality of Life Questionnaire............................................... 86
Appendix 9 EuroQol 5-Dimension 5-Level Questionnaire................................... 93
Appendix 10 Medical Outcomes Study Sleep Scale........................................... 95
Appendix 11 Healthy Days Core Module............................................................ 97
Appendix 12 Sampson's Criteria for Diagnosing Potential Cases of 
Anaphylaxis................................................................................. 98

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PROTOCOL ACCEPTANCE FORM
TITLE:
OPEN-LABEL EXTENSION STUDY OF 
OMALIZUMAB IN PATIENTS WITH CHRONIC 
RHINOSINUSITIS WITH NASAL POLYPS
PROTOCOL NUMBER:
WA40169
VERSION NUMBER:
1
EUDRACT NUMBER:
2017-003450-16
IND NUMBER:
5369
TEST PRODUCT:
Omalizumab (IGE025)
MEDICAL MONITOR:
, M.D.
SPONSOR:
F. Hoffmann-La Roche Ltd
I agree to conduct the study in accordance with the current protocol.
Principal Investigator's Name  (print)
Principal Investigator's Signature
Date
Please retain the signed original of this form for your study files.  Please return a copy of 
the signed form as instructed by your local study monitor.

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PROTOCOL SYNOPSIS
TITLE:
OPEN-LABEL EXTENSION STUDY OF OMALIZUMAB IN 
PATIENTS WITH CHRONIC RHINOSINUSITIS WITH NASAL 
POLYPS
PROTOCOL NUMBER:
WA40169
VERSION NUMBER:
1
EUDRACT NUMBER:
2017-003450-16
IND NUMBER:
5369
TEST PRODUCT:
Omalizumab (IGE025)
PHASE:
3
INDICATION:
Chronic rhinosinusitis with nasal polyps
SPONSOR:
F. Hoffmann-La Roche Ltd
Objectives and Endpoints
The overall purpose of this study is to evaluate the safety, efficacy, and durability of response of 
omalizumab in an open-label setting in adult patients with chronic rhinosinusitis with nasal 
polyps (CRSwNP) who completed the double-blind placebo-controlled Phase III Study GA39688
or GA39855.  Specific objectives and corresponding endpoints for the study are outlined below.
Primary Safety Objective
Corresponding Endpoints
To evaluate adverse events 
associated with usage of omalizumab
in patients with CRSwNP

Incidence of serious and non-serious adverse events

Incidence of adverse events leading to omalizumab 
discontinuation
Secondary Safety Objective
Corresponding Endpoint
To evaluate any potential laboratory 
abnormalities associated with usage 
of omalizumab in patients with 
CRSwNP

Clinically significant change in laboratory values
Primary Efficacy Objective
Corresponding Endpoints a
To evaluate efficacy of continued 
treatment with omalizumab after an 
initial 24-week treatment period
Change from baseline at Weeks 4 b, 8 b, 16 b, 24 b, 36, 
and 52 in NPS
Change from baseline at Weeks 4 b, 8 b, 12 b, 16 b, 20 b, 
24 b, 28, 32, 36, 40, 44, 48, and 52 in NCS
To evaluate the durability of response 
following treatment discontinuation
Change from baseline at Weeks 52, 64, and 76 in NPS 
Change from baseline at Weeks 52, 56, 60, 64, 68, 72, 
and 76 in NCS

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Secondary Efficacy Objectives
Corresponding Endpoints a
To evaluate the impact of treatment 
duration with omalizumab on durability 
of response
Change from baseline at Week 76 in the following 
assessments: 
–
NPS
–
NCS
–
TNSS
–
Loss of smell
–
Posterior rhinorrhea
–
Anterior rhinorrhea
–
SNOT-22
–
EQ-5D-5L
–
AQLQ (patients with comorbid asthma only)
–
UPSIT
To evaluate efficacy of continued 
treatment with omalizumab after an 
initial 24-week treatment period
Change from baseline at Weeks 4 b, 8 b, 12 b, 16 b, 20 b, 
24 b, 28, 32, 36, 40, 44, 48, and 52 in the following 
assessments:
–
TNSS
–
Posterior rhinorrhea
–
Anterior rhinorrhea
–
Loss of smell
Change from baseline at Weeks 4 b, 8 b, 16 b, 24 b, 36, 
and 52 in the following assessments:
–
SNOT-22
–
AQLQ (patients with comorbid asthma only)
Change from baseline at Weeks 16 b, 24 b, 36, and 52 in 
EQ-5D-5L
Change from baseline at Weeks 8 b, 16 b, 24 b, 36, and 52 
in UPSIT

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Secondary Efficacy Objectives (cont.)
Corresponding Endpoints a (cont.)
To evaluate the durability of response 
following treatment discontinuation
Change from baseline at Weeks 52, 56, 60, 64, 68, 72, 
and 76 in the following assessments:
–
TNSS
–
Posterior rhinorrhea
–
Anterior rhinorrhea
–
Loss of smell
Change from baseline at Weeks 64 and 76 in SNOT-22
Change from baseline at Weeks 52, 64, and 76 in the 
following assessments: 
–
EQ-5D-5L
–
AQLQ (in patients with comorbid asthma only)
–
UPSIT
Exploratory Efficacy Objectives
Corresponding Endpoints
To evaluate efficacy of continued 
treatment with omalizumab after an 
initial 24-week treatment period
Reduction in the need for surgery by Weeks 36 and 52, 
as defined by an NPS of 4 (unilateral score of 2 on 
each side) and improvement in SNOT-22 score of 8.9
Requirement of rescue treatment (systemic CS 
for 3 consecutive days) or having had surgery for nasal 
polyps through Week 52
Requirement of rescue treatment (systemic CS 
for 3 consecutive days) through Week 52
Having had surgery for nasal polyps through Week 52
To evaluate the effect of omalizumab 
on sleep quality after an initial 24-week 
treatment period of placebo
Change from Week 24 at Weeks 36, 52, 64, and 76 in 
MOS Sleep Scale
To evaluate the effect of omalizumab 
on overall physical and mental health 
after an initial 24-week treatment 
period of placebo

Change from Week 24 at Weeks 36, 52, 64, and 76 in 
Healthy Days Core Module
Exploratory Psychometric 
Objective
Corresponding Endpoint
To collect data to support 
psychometric analyses to assess 
sensitivity of EQ-5D-5L

PGIC at Weeks 36, 52, 64, and 76
AQLQAsthma Quality of Life Questionnaire; CRSwNPchronic rhinosinusitis with nasal polyps; 
EQ-5D-5LEuroQol 5-Dimension 5-Level Questionnaire; MOS Medical Outcomes Study; 
NCSnasal blockage/congestion score; NPSnasal polyp score; PGICPatient Global Impression 
of Change; SNOT-22Sino-Nasal Outcome Test-22; TNSStotal nasal symptom score; 
UPSIT University of Pennsylvania Smell Identification Test.
a Baseline is defined as the last pre-treatment measurement prior to randomization in 
Studies GA39688/GA39855 (i.e., baseline of Studies GA39688/GA39855). 
b These data are from Studies GA39688/GA39855.

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Study Design
Description of Study
This study is an open-label clinical study.  Patients who have completed the treatment period of 
Study GA39688/GA39855 and fulfill the eligibility criteria for the open-label extension (OLE) 
study will be enrolled. 
Patients will be eligible for enrollment in the study at the Week 24 visit of 
Study GA39688/GA39855 or within 28 days after the Week 24 visit of 
Study GA39688/GA39855.  Whenever possible, patients should enroll and begin open-label 
dosing of omalizumab at the Week 24 visit of Study GA39688/GA39855 rather than return for a 
subsequent visit.  However, if necessary, patients may return within 28 days of the Week 24 
visit of Study GA39688/GA39855 to enroll and begin dosing.  The rationale for enrolling patients 
into this OLE study at the Week 24 visit of Study GA39688/GA39855, or within a short period of 
time thereafter, is to allow for relatively continuous exposure to omalizumab over a 52-week 
period of time.  Enrollment at the Week 24 visit of Study GA39688/GA39855 may also reduce 
patient burden by obviating the need for an additional clinic visit.
Informed consent into this OLE study must be completed by the time of enrollment and 
open-label omalizumab dosing.  Whenever possible, investigators should begin the consent 
process for this OLE study well in advance of the Week 24 visit of Study GA39688/GA39855.  
Providing information about this OLE study to patients early in Study GA39688/GA39855 will 
facilitate a seamless transition into this protocol. 
After enrollment into this OLE study, patients will receive 28 weeks of dosing of open-label 
omalizumab before entering a 24-week off-treatment observation phase of the study.  In this 
protocol, the timing of the visit schedule for this OLE study is defined in time relative to the 
baseline of Study GA39688/GA39855.  That is, the first visit of this OLE study is referred to as 
the "Week 24 Visit."  Similarly, the last visit occurring during the 28-week treatment phase is 
referred to as the "Week 52 Visit," and the final visit of the 24-week follow-up period is referred 
to as the "Week 76 Visit."  Note that the Week 52 Visit is not only considered to be the last visit 
of the treatment phase, but also the first visit of the follow-up period.
The first dose of open-label omalizumab should be administered on the day of enrollment into 
this OLE study ("Week 24 Visit").  The dosing table will be the same as that used with 
Study GA39688/GA39855.
Patients should remain on stable doses of intranasal corticosteroid (CS) therapy (mometasone 
nasal spray 200 g twice a day [BID]) for the entire treatment and follow-up periods.  That is, 
patients should remain on stable doses of intranasal CS therapy for both the treatment period of 
Study GA39688/GA39855, the treatment period of this current study, and the follow-up period of 
this current study.  As in Study GA39688/GA39855, patients deemed by the investigator to be 
intolerant to a BID regimen of mometasone may remain on a stable dosage of mometasone 
once daily (QD) (two sprays/nostril, both nostrils, 50 g/spray QD for a total daily dosage of 
200 g).  Any patient transitioned to daily mometasone should remain on this regimen for the 
remainder of the study.  
Safety, efficacy, and patient-reported outcome (PRO) measures will be assessed during the 
treatment and follow-up periods, as detailed in the schedule of activities.  
After the treatment period ends (after Week 52 Visit), patients will be followed for an additional 
24 weeks as part of the follow-up period.  There is no dose administered at Week 52.  During 
the follow-up period, patients will be asked to continue completion of their daily electronic diary 
(eDiary) assessment of nasal symptoms.  An important objective of this portion of this study will 
be to understand the extent and timing of any relapse in symptoms related to nasal polyposis.  
Patients will return to clinic at Week 64 and for a final visit at Week 76, with telephone visits at 
Weeks 56, 60, 68, and 72. 
All patients who discontinue study drug early during the treatment period will be asked to 
complete the remainder of the treatment period and then complete the 24-week follow-up 
period.  For example, if a patient discontinues study drug at Week 32, that patient would be 
asked to return for the Week 36 and Week 52 visits to complete all assessments and would 
then complete the follow-up visits. 
Nasal polyp score (NPS) will be assessed by video nasal endoscopy, scored using a standard 
scoring system (maximum NPS is 8) by a central panel of independent sinus surgeons who are 

 
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blinded to treatment assignment from Studies GA39688/GA39855 and blinded to timepoint of 
assessment within this OLE study (e.g., readers will not know whether nasal endoscopy was 
obtained during the treatment period or the follow-up period).  
Number of Patients 
All subjects completing Week 24 of Study GA39688/GA39855 and otherwise meeting inclusion 
and exclusion criteria are eligible to enroll.  It is anticipated that a maximum of approximately 
240 patients will enroll into this study. 
Target Population 
Inclusion Criteria 
Patients must meet the following criteria for study entry: 
 
Signed Informed Consent Form 
 
Age 1875 years old, inclusive, at time of signing informed consent form for 
Study GA39688 or Study GA39855 
 
Ability to comply with the study protocol, in the investigator's judgment 
 
Participation in Study GA39688 or Study GA39855, including completion of endoscopy and 
other assessments at Week 24, without discontinuation of study drug 
 
Completion of eDiary daily assessments for at least 4 out of 7 days in the week prior to the 
Week 24 visit of Study GA39688 or Study GA39855 
 
For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use acceptable contraceptive methods during the treatment 
period and for 60 days after the last dose of study drug 
– 
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the 
patient.  Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception. 
– 
Acceptable methods of contraception include surgical sterilization (e.g., bilateral tubal 
ligation, vasectomized partner), hormonal contraception (e.g., implantable, injectable, 
patch, oral), and intrauterine device (IUD).  
– 
Women of childbearing potential must have a negative pregnancy test result prior to 
initiation of study drug in this study. 
 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
 
Anaphylaxis/hypersensitivity related to study drug in Study GA39688/GA39855 
 
Serious adverse events related to study drug in Study GA39688/GA39855 that the 
investigator or Sponsor determines may jeopardize the patient's safety if he or she 
continues in the study 
 
Uncontrolled epistaxis within Study GA39688 or GA39855 
 
Pregnant or breastfeeding, or intending to become pregnant during the study or within 
60 days after the last dose of omalizumab 
 
Any serious medical condition or abnormality in clinical laboratory tests that, in the 
investigator's judgment, precludes the patient's safe participation in and completion of the 
study 
 
End of Study and Length of Study 
The end of the study is defined as the date of the last patient's last visit (LPLV).  The LPLV is 
expected to occur approximately 52 weeks after the last patent is enrolled (28-week treatment 
period of OLE followed by 24-week follow-up period).  
Investigational Medicinal Products 
The investigational medicinal product (IMP) for this study is omalizumab. 

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Test Product (Investigational Drug)
Study drug (omalizumab) will be administered subcutaneously to patients using a disposable 
25-gauge needle in the deltoid region of the right or left arm.  Alternatively, the injections can be 
administered in the thigh, if medically significant reasons preclude administration in the deltoid 
region.
Omalizumab will be administered subcutaneously every 2 or 4 weeks.  Because the solution is 
slightly viscous, the injection may take 510 seconds to administer.  The dose (mg) and dosing 
frequency will be determined by serum total IgE level (IU/mL) (measured before the start of 
treatment via central laboratory) and body weight (kg).  Assignment of omalizumab dose will be 
determined by using the study drugdosing table.  Doses of 150 mg are divided among more 
than one injection site to limit injections to no more than 150 mg per site.  The reconstituted vial 
is to be used for single-dose administration only.
Non-Investigational Medicinal Products
In this study, mometasone furoate monohydrate nasal spray is considered a non-IMP and is 
used as background therapy only.
Statistical Methods
Primary Analysis
The analysis of complete data from the study, including data from the safety follow-up period,
will be performed when all patients have either discontinued the study early or completed the 
safety follow-up period, all data from the study are in the database, and the database is cleaned 
and locked.  
Determination of Sample Size
No formal sample size calculation was performed for this study because the primary analysis is 
descriptive in nature, there will be no formal hypothesis testing, and this study is an OLE of 
previous studies (Studies GA39688 and GA39855), which plan to enroll approximately 240 
patients in total (120 patients each).  In order to be eligible for enrollment into this study, the 
patient must complete assessments at Week 24 in the prior study without discontinuation of 
study drug.  Therefore, due to the inclusion criteria of this study and potential dropout from 
Studies GA39688 and GA39855, the sample size of approximately 240 patients is a maximum.

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
ADA
anti-drug antibody
AERD
aspirin-exacerbated respiratory disease
AQLQ
Asthma Quality of Life Questionnaire
AQLQ(S)
standardized Asthma Quality of Life Questionnaire
ATEs
arterial thrombotic events
BID
twice a day
CIU
chronic idiopathic urticaria
CRO
contract research organization
CRS
chronic rhinosinusitis
CRSwNP
chronic rhinosinusitis with nasal polyps
CS
corticosteroid
CSU
chronic spontaneous urticaria
EC
Ethics Committee
eCRF
electronic Case Report Form
EDC
electronic data capture
eDiary
electronic diary
EQ-5D-5L
EuroQol 5-Dimension 5-level Questionnaire
EXCELS
Epidemiologic Study of Xolair (omalizumab): Evaluating 
Clinical Effectiveness and Long-term Safety in Patients 
with Moderate-to-Severe Asthma
FAS-OLE
full analysis set of the OLE study
FDA
Food and Drug Administration
FESS
functional endoscopic sinus surgery
HIPAA
Health Insurance Portability and Accountability Act
HRQoL
health-related quality of life
ICH
International Council for Harmonisation
iDMC
independent Data Monitoring Committee
IL
interleukin
IMP
investigational medicinal product
IND
Investigational New Drug (Application)
IRB
Institutional Review Board
IWRS
interactive web-based response system
LPLV
last patient, last visit
MMRM
mixed-effect model repeated measurement
MOS
Medical Outcomes Study
NCS
nasal blockage/congestion score

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NPS
nasal polyp score
OLE
open-label extension
PGIC
Patient Global Impression of Change
PK
pharmacokinetic
PRO
patient-reported outcome
QD
once daily
QoL
quality of life
SAP
Statistical Analysis Plan
SmPC
Summary of Product Characteristics
SNOT-22
Sino-Nasal Outcome Test-22
SWFI
Sterile Water for Injection
TNSS
total nasal symptom score
ULN
upper limit of normal
UPSIT
University of Pennsylvania Smell Identification Test

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1.
BACKGROUND
1.1
BACKGROUND ON CHRONIC RHINOSINUSITIS WITH NASAL 
POLYPS
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly adult disease with 
a prevalence estimated to be 2.1%2.7% (Johansson et al. 2003; Klossek et al. 2005; 
We et al. 2015).  It is associated with reduced quality of life (QoL) and significant 
morbidity, including asthma, which can be severe and refractory, particularly in those 
patients with aspirin-exacerbated respiratory disease (AERD) (Hulse et al. 2014; 
Stevens and Schleimer 2016).
The diagnosis of CRSwNP is made in patients who exhibit a combination of symptoms 
(e.g., blockage/congestion, anterior or postnasal drip, and impaired sense of smell) in the 
presence of nasal polyps (Fokkens et al. 2012; Rimmer et al. 2014).  Intranasal and 
systemic/oral corticosteroids remain the mainstay of treatment, but many patients fail to 
achieve complete therapeutic benefit with these medications and resort to functional 
endoscopic sinus surgery (FESS) and other complex sinus surgery (Fokkens et al. 2012; 
Rimmer et al. 2014).  Although FESS and intranasal and oral corticosteroids are useful 
and often effective in reducing the size of nasal polyps and associated symptoms, many 
patients do not respond sufficiently and/or polyps return rapidly after medication 
withdrawal or within months or years following surgery.  In one trial, almost 40% of 
patients who received daily intranasal corticosteroids (mometasone furoate) following 
FESS suffered a relapse within 6 months of the procedure (Stjärne et al. 2009).  In another 
study, almost 50% of the patients who received oral corticosteroids in combination with 
topical therapy suffered a relapse within 12 months of treatment (Cassano et al. 1996).  
Moreover, oral corticosteroids are associated with significant side effects, and repeat 
surgical procedures become progressively more complex and risky.  In the United States, 
the only approved pharmacotherapy for nasal polyps is intranasal corticosteroids 
(mometasone furoate and/or beclomethasone). Because of limitations in treatment, 
combined with QoL that is considerably reduced in CRSwNP patients, nasal polyposis 
remains an important unmet medical need (Hulse et al. 2015).  
Patients with CRSwNP and most patients with asthma share a common IgE-mediated 
type 2 inflammatory response, characterized by elevated levels of interleukin (IL)-4, IL-5, 
IL-13, eosinophils, Th2 cells, and type 2 innate lymphoid cells (Wenzel et al. 1999; 
Kato 2015).  In addition, locally produced IgEoften against Staphylococcus aureus
enterotoxinsis associated with local inflammation in CRSwNP and, in particular, with 
comorbid asthma (Bachert et al. 2010).  Because of the common type 2 inflammatory 
disease between asthma and CRSwNP, approximately 20%30% of patients with asthma 
have CRSwNP, particularly those patients with AERD.  In addition, a substantial proportion 
of patients with CRSwNP have symptoms of asthma, with higher percentages associated 
with patients who have greater nasal polyp disease severity (Settipane 1987; Larsen 1996; 
Hedman et al. 1999; Johansson et al. 2003; Ragab et al. 2004; Pearlman et al. 2009; 
Promsopa et al. 2016).  Importantly, there appears to be a premorbid relationship between 

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asthma and CRSwNP, with the diagnosis of asthma often occurring prior to that of nasal 
polyposis (Larsen 1996; Tan et al. 2013; Lam et al. 2014). 
1.2
BACKGROUND ON OMALIZUMAB
Omalizumab (Xolair®) is a recombinant DNA-derived humanized IgG1 monoclonal 
antibody with a molecular mass of approximately 149 kDa that selectively binds to 
human IgE.
Omalizumab is designed to treat IgE-mediated disease by reducing the concentration of 
free IgE in blood and in tissue.  Omalizumab selectively binds to human IgE at the same 
site as does the high affinity IgE receptor (FcRI) (Schulman 2001), thereby reducing 
surface-bound IgE through this receptor on basophils and mast cells, reducing 
cross-linking of IgE to the receptor when antigen is bound and the subsequent basophil 
and mast cell triggered type 2 inflammation.
Omalizumab was approved by the U.S. Food and Drug Administration (FDA) for allergic 
asthma in 2003 and for chronic idiopathic urticaria (CIU), also known as chronic 
spontaneous urticaria (CSU), in 2014.
Refer to the Omalizumab Investigator's Brochure for details on nonclinical and clinical 
studies.
1.3
STUDY RATIONALE AND BENEFITRISK ASSESSMENT
This study will assess the long-term safety and tolerability of omalizumab every 2 or 
4 weeks with regard to adverse events and laboratory abnormalities and will also obtain 
long-term data on the efficacy of omalizumab in patients with CRSwNP after 
participation in the Phase III studies (GA39688 or GA39855). Patients will enroll in this 
study following the completion of the Phase III, double-blind, placebo-controlled 
Study GA39688 or GA39855.
Eligible patients receiving omalizumab or placebo in the controlled Phase III study will 
receive active omalizumab in this study for approximately 28 weeks followed by an 
approximately 24-week post-treatment follow-up period. Eligibility criteria and the 
timepoints for enrollment in this study are described in Section 4.1.
1.3.1
BenefitRisk Assessment
CRSwNP occurs in a subset of patients with chronic rhinosinusitis (CRS).  The polyps 
that develop in patients with CRSwNP are characterized histologically by the presence 
of large numbers of eosinophils and type 2 innate lymphoid cells as well as by mucosal 
edema and albumin containing pseudocysts with minimal extracellular matrix fibrosis 
(Huvenne et al. 2009; Mjösberg et al. 2011).  In contrast, nasal polyps associated with 
other diseases (e.g., cystic fibrosis) are associated with large numbers of neutrophils in 
the polyp tissue.  The polyps in patients with CRSwNP exhibit a type 2 cytokine profile, 
with predominant expression of IL-13, IL-5, and some IL-4 (Wang et al. 2015).  Activated 

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B cells produce IgE, often against Staphylococcus aureus, in association with increased 
mucus and chemokine production.  The marked local production of IgE antibodies in 
patients with CRSwNP appears to be functional and involved in the regulation of chronic 
inflammation (Zhang et al. 2011). Asthma and CRSwNP may share similar type 2 
cytokine profiles, such that a substantial proportion of patients with CRSwNP exhibit 
comorbid asthma.  In turn, a substantial proportion of patients with asthma have 
CRSwNP, particularly among those with more severe asthma (Settipane 1987; 
Larsen 1996; Ragab et al. 2004; Pearlman et al. 2009; Langdon and Mullol 2016).
Omalizumab interrupts the allergic cascade triggered by cross-linking IgE on the surface 
of mast cells and basophils by 1) forming complexes with IgE and preventing the arming 
of effector cells; 2) aiding off-loading of mast cells and basophils by trapping IgE as it 
dissociates from the FcRI receptor; 3) down-modulating FcRI (on mast cells, basophils, 
and dendritic cells) as a direct consequence of the reduction in free IgE levels; 
4) reducing antigen presentation to T lymphocytes by dendritic cells; 5) reducing IgE 
stimulated synthesis and secretion of proinflammatory cytokines by human airway 
smooth muscle cells; and 6) improving interferon-production by plasmacytoid dendritic 
cells (Presta et al.1993; Jardieu 1995; Heusser and Jardieu 1997; Holgate et al. 1998; 
Fick 1999; Jardieu and Fick 1999; Patalano 1999; Boushey 2001; Prussin et al. 2003; 
Roth and Tamm 2010; Teach et al. 2015).  These events then result in the reduction of 
type 2 inflammation, including reduced production of IL-4, IL-5, and IL-13 by innate and 
adaptive cells.  Therefore, given the multiple potential mechanisms of omalizumab in 
limiting the inflammation in nasal polyps, a strategy to antagonize IgE with omalizumab 
is likely to benefit patients with CRSwNP. 
The benefit of antagonizing IgE in patients with CRSwNP has also been suggested by a 
randomized, double-blind, placebo-controlled study in patients with nasal polyps and 
comorbid asthma published by Gevaert et al. 2013.  Twenty-four patients (nasal polyp 
size 5) were included and randomized 2:1 to receive omalizumab or placebo for 
16 weeks.  Twelve of the 24 patients had the diagnosis of aspirin hypersensitivity.  
Results showed a significant reduction from baseline in total nasal endoscopic polyp 
score in patients in the omalizumab group at Week 16 (-2.67, p0.001) but not in 
patients in the placebo group (-0.12, p0.99).  In addition, omalizumab treatment 
improved computed tomography image scores; reduced symptom scores for nasal 
congestion, anterior rhinorrhea, loss of sense of smell, wheeze, and dyspnea; and 
improved QoL scores, all irrespective of the presence of allergy (Gevaert et al. 2013).
A number of other case-controlled and randomized, double-blind, placebo-controlled 
studies have been performed over the past decade examining the efficacy of 
omalizumab for the treatment of nasal polyps (Penn and Mikula 2007; Pinto et al. 2010; 
Vennera et al. 2011; Tajiri et al. 2013; Sintobin et al. 2015).  The collective and 
cumulative clinical evidence strongly suggests a potential benefit of omalizumab in 
patients with CRSwNP.

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Omalizumab is being investigated in placebo-controlled randomized clinical trials 
(Studies GA39688 and GA39855), which will provide the source population for this 
current extension study.  These studies are enrolling patients with difficult-to-treat 
CRSwNP, large bilateral nasal polyps, and substantial burden to their heath-related 
quality of life (HRQoL).  As such, it is anticipated that patients may potentially require 
longer-term treatment of their CRSwNP with a biologic medication and that the usage of 
such biologic medications longer than 24 weeks may be warranted in some situations.  
Moreover, omalizumab may be utilized longer term for the other two indications for which 
it is approved: allergic asthma and CIU/CSU.  There is indeed significant evidence 
regarding omalizumab's longer-term safety profile, including the Epidemiologic Study of 
Xolair (Omalizumab): Evaluating Clinical Effectiveness and Long-Term Safety in Patients 
with Moderate-to-Severe Asthma (EXCELS), a prospective observational cohort study of 
adults and adolescents with allergic asthma with a median follow-up of 5 years including 
5007 patients in an omalizuamb cohort and 2829 patients in a comparator 
non-omalizumab cohort (Long et al. 2014).  
Thus, the studies that provide evidence for potential effectiveness of anti-IgE therapy in 
CRSwNP, the enrollment of difficult-to-treat patients with significant disease burden, the 
established safety profile of omalizumab, and omalizumab's frequent longer-term usage 
in other indications provide evidence for the benefitrisk assessment of conducting the 
current extension study. 
2.
OBJECTIVES AND ENDPOINTS
The overall purpose of this study is to evaluate the safety, efficacy, and durability of 
response of omalizumab in an open-label setting in adult patients with CRSwNP who 
completed the double-blind, placebo-controlled Phase III Study GA39688 or GA39855.  
Specific objectives and corresponding endpoints for the study are outlined below (see 
Table 1).
Table 1
Objectives and Corresponding Endpoints
Primary Safety Objective
Corresponding Endpoints
To evaluate adverse events 
associated with usage of omalizumab
in patients with CRSwNP
Incidence of serious and non-serious adverse events
Incidence of adverse events leading to omalizumab 
discontinuation
Secondary Safety Objective
Corresponding Endpoint
To evaluate any potential laboratory 
abnormalities associated with usage 
of omalizumab in patients with 
CRSwNP 

Clinically significant change in laboratory values

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Primary Efficacy Objective
Corresponding Endpoints a
To evaluate efficacy of continued 
treatment with omalizumab after an 
initial 24-week treatment period
Change from baseline at Weeks 4 b, 8 b, 16 b, 24 b, 36, 
and 52 in NPS
Change from baseline at Weeks 4 b, 8 b, 12 b, 16 b, 20 b, 
24 b, 28, 32, 36, 40, 44, 48, and 52 in NCS
To evaluate the durability of response 
following treatment discontinuation
Change from baseline at Weeks 52, 64, and 76 in NPS 
Change from baseline at Weeks 52, 56, 60, 64, 68, 72, 
and 76 in NCS
Secondary Efficacy Objectives
Corresponding Endpoints a
To evaluate the impact of treatment 
duration with omalizumab on durability 
of response
Change from baseline at Week 76 in the following 
assessments: 
–
NPS
–
NCS
–
TNSS
–
Loss of smell
–
Posterior rhinorrhea
–
Anterior rhinorrhea
–
SNOT-22
–
EQ-5D-5L
–
AQLQ (patients with comorbid asthma only)
–
UPSIT
To evaluate efficacy of continued 
treatment with omalizumab after an 
initial 24-week treatment period
Change from baseline at Weeks 4 b, 8 b, 12 b, 16 b, 20 b, 
24 b, 28, 32, 36, 40, 44, 48, and 52 in the following 
assessments:
–
TNSS
–
Posterior rhinorrhea
–
Anterior rhinorrhea
–
Loss of smell
Change from baseline at Weeks 4 b, 8 b, 16 b, 24 b, 36, 
and 52 in the following assessments:
–
SNOT-22
–
AQLQ (patients with comorbid asthma only)
Change from baseline at Weeks 16 b, 24 b, 36, and 52 in 
EQ-5D-5L
Change from baseline at Weeks 8 b, 16 b, 24 b, 36, and 52 
in UPSIT

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Secondary Efficacy Objectives (cont.)
Corresponding Endpoints a (cont.)
To evaluate the durability of response 
following treatment discontinuation
Change from baseline at Weeks 52, 56, 60, 64, 68, 72, 
and 76 in the following assessments:
–
TNSS
–
Posterior rhinorrhea
–
Anterior rhinorrhea
–
Loss of smell
Change from baseline at Weeks 64 and 76 in SNOT-22
Change from baseline at Weeks 52, 64, and 76 in the 
following assessments: 
–
EQ-5D-5L
–
AQLQ (in patients with comorbid asthma only)
–
UPSIT
Exploratory Efficacy Objectives
Corresponding Endpoints
To evaluate efficacy of continued 
treatment with omalizumab after an 
initial 24-week treatment period
Reduction in the need for surgery by Weeks 36 and 52, 
as defined by an NPS of 4 (unilateral score of 2 on 
each side) and improvement in SNOT-22 score of 8.9
Requirement of rescue treatment (systemic CS 
for 3 consecutive days) or having had surgery for nasal 
polyps through Week 52
Requirement of rescue treatment (systemic CS 
for 3 consecutive days) through Week 52
Having had surgery for nasal polyps through Week 52
To evaluate the effect of omalizumab 
on sleep quality after an initial 24-week 
treatment period of placebo
Change from Week 24 at Weeks 36, 52, 64, and 76 in 
MOS Sleep Scale
To evaluate the effect of omalizumab 
on overall physical and mental health 
after an initial 24-week treatment 
period of placebo
Change from Week 24 at Weeks 36, 52, 64, and 76 in 
Healthy Days Core Module
Exploratory Psychometric 
Objective
Corresponding Endpoint
To collect data to support 
psychometric analyses to assess 
sensitivity of EQ-5D-5L 

PGIC at Weeks 36, 52, 64, 76
AQLQAsthma Quality of Life Questionnaire; CRSwNPchronic rhinosinusitis with nasal polyps; 
EQ-5D-5LEuroQol 5-Dimension 5-Level Questionnaire; MOS Medical Outcomes Study; 
NCSnasal blockage/congestion score; NPSnasal polyp score; PGICPatient Global Impression 
of Change; SNOT-22Sino-Nasal Outcome Test-22; TNSStotal nasal symptom score; 
UPSIT University of Pennsylvania Smell Identification Test.
a Baseline is defined as the last pre-treatment measurement prior to randomization in
Studies GA39688/GA39855 (i.e., baseline of Studies GA39688/GA39855). 
b These data are from Studies GA39688/GA39855.

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3.
STUDY DESIGN
3.1
DESCRIPTION OF THE STUDY
This study is an open-label clinical study.  Patients who have completed the treatment 
period of Study GA39688/GA39855 and fulfill the eligibility criteria for the open-label 
extension (OLE) study will be enrolled. 
Written informed consent for participation in the study must be obtained before 
performing any study-specific tests or evaluations.  Patients will then start receiving 
open-label omalizumab as per the dosing schedule based on their body weight and IgE 
levels collected during the screening period of Study GA39688/GA39855 (see Figure 1).  
Patients will also undergo assessments as shown in the schedules of activities in
Appendix 1.
Patients will be eligible for enrollment in the study at the Week 24 visit of 
Study GA39688/GA39855 or within 28 days after the Week 24 visit of 
Study GA39688/GA39855.  Whenever possible, patients should enroll and begin 
open-label dosing of omalizumab at the Week 24 visit of Study GA39688/GA39855 
rather than return for a subsequent visit.  However, if necessary, patients may return 
within 28 days of the Week 24 visit of Study GA39688/GA39855 to enroll and begin 
dosing.  The rationale for enrolling patients into this OLE study at the Week 24 visit of 
Study GA39688/GA39855, or within a short period of time thereafter, is to allow for 
relatively continuous exposure to omalizumab over a 52-week period of time.  
Enrollment at the Week 24 visit of Study GA39688/GA39855 may also reduce patient 
burden by obviating the need for an additional clinic visit.
Informed consent into this OLE study must be completed by the time of enrollment and 
open-label omalizumab dosing.  Whenever possible, investigators should begin the 
consent process for this OLE study well in advance of the Week 24 visit of 
Study GA39688/GA39855.  Providing information about this OLE study to patients early 
in Study GA39688/GA39855 will facilitate a seamless transition into this protocol.
After enrollment into this OLE study, patients will receive 28 weeks of dosing of 
open-label omalizumab before entering a 24-week off-treatment observation phase of 
the study.  In this protocol, the timing of the visit schedule for this OLE study is defined in 
time relative to the baseline of Study GA39688/GA39855.  That is, the first visit of this 
OLE study is referred to as the "Week 24 Visit."  Similarly, the last visit occurring during 
the 28-week treatment phase is referred to as the "Week 52 Visit," and the final visit of 
the 24-week follow-up period is referred to as the "Week 76 Visit."  Note that the 
Week 52 Visit is not only considered to be the last visit of the treatment phase, but also 
the first visit of the follow-up period.

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The first dose of open-label omalizumab should be administered on the day of 
enrollment into this OLE study ("Week 24 Visit").  The dosing table will be the same as 
that used with Study GA39688/GA39855 (see Appendix 2).
Patients should remain on stable doses of intranasal corticosteroid (CS) therapy 
(mometasone nasal spray 200 g twice a day [BID] as per Section 4.3.3) for the entire 
treatment and follow-up periods.  That is, patients should remain on stable doses of 
intranasal CS therapy for both the treatment period of Study GA39688/GA39855, the 
treatment period of this current study, and the follow-up period of this current study.  As 
in Study GA39688/GA39855, patients deemed by the investigator to be intolerant to a 
BID regimen of mometasone may remain on a stable dosage of mometasone once daily 
(QD) (two sprays/nostril, both nostrils, 50 g/spray QD for a total daily dosage of 200 g).  
Any patient transitioned to daily mometasone should remain on this regimen for the 
remainder of the study. 
Safety, efficacy, and patient-reported outcome (PRO) measures will be assessed during 
the treatment and follow-up periods, as detailed in the schedule of activities (see 
Appendix 1).  
After the treatment period ends (after Week 52 Visit), patients will be followed for an 
additional 24 weeks as part of the follow-up period (Appendix 1). There is no dose 
administered at Week 52.  During the follow-up period, patients will be asked to continue 
completion of their daily electronic diary (eDiary) assessment of nasal symptoms. An 
important objective of this portion of this study will be to understand the extent and 
timing of any relapse in symptoms related to nasal polyposis.  Patients will return to 
clinic at Week 64 and for a final visit at Week 76, with telephone visits at Weeks 56, 60, 
68, and 72. 
All patients who discontinue study drug early during the treatment period will be asked to 
complete the remainder of the treatment period and then complete the 24-week 
follow-up period. For example, if a patient discontinues study drug at Week 32, that 
patient would be asked to return for the Week 36 and Week 52 visits to complete 
all assessments and would then complete the follow-up visits. 
NPS will be assessed by video nasal endoscopy, scored using a standard scoring 
system (Appendix 3; maximum NPS is 8) by a central panel of independent sinus 
surgeons who are blinded to treatment assignment from Studies GA39688/GA39855 and 
blinded to timepoint of assessment within this OLE study (e.g., readers will not know 
whether nasal endoscopy was obtained during the treatment period or the follow-up 
period).
A schedule of activities is provided in Appendix 1.

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Figure 1
Study Schema
OLEopen-label extension; Q2W every 2 weeks; Q4W every 4 weeks.
a The timing of the visit schedule is defined in time relative to the baseline of 
Study GA39688/GA39855.  Thus, the open-label treatment period of this study is 28 weeks 
and runs from the "Week 24 Visit" (approximately 24 weeks after initiation of study drug in 
Study GA39688/GA39855) to the "Week 52 Visit" (approximately 52 weeks after initiation of 
study drug in Study GA39688/GA39855).
3.2
END OF STUDY AND LENGTH OF STUDY
The end of the study is defined as the date of the last patient's last visit (LPLV).  The 
LPLV is expected to occur approximately 52 weeks after the last patent is enrolled
(28-week treatment period of OLE followed by 24-week follow-up period).
3.3
RATIONALE FOR STUDY DESIGN
3.3.1
Rationale for Omalizumab Dose and Schedule
In this study, patient weights and IgE values used to determine study drug dosing will be 
based only on values from the screening period of Study GA39688/GA39855 (see 
Section 4.1.3 for further details).  Omalizumab will be dosed according to the same 
dosing table used in Study GA39688/GA39855.  That is, dosing will be based on a 
dosing table that provides at least 0.016 mg/kg for every IU/mL of IgE, within a 4-week 
interval (see Appendix 2).  The dosing algorithm used as the basis of the dosing table is 
consistent with the approach used in published studies for the treatment of CRSwNP
and with the approach used for the treatment of allergic asthma.  The range of IgE 
values (30 IU/mL to 1,500 IU/mL) used in the dosing table comes from the asthma 
E.U. SmPC dosing table.  This asthma E.U. SmPC table has been modified to remove 
lower patient weights because this trial will include only adult patients, whereas the 
approved asthma E.U. SmPC table is also intended to treat pediatric patients.  As with 
the approved E.U. SmPC table, omalizumab will be administered every 4 weeks for 
doses up to and including 600 mg and every 2 weeks for those patients requiring higher 
doses (see Appendix 2). 

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3.3.2
Rationale for Open-Label Study Design
For the purposes of efficacy analyses, this study utilizes endpoints such as nasal 
blockage/congestion score (NCS) and NPS with continuous outcomes scales rather than 
binary event rates. These outcomes are evaluated over time, as detailed in Section 6.6, 
allowing an examination of the extent to which patients improve or worsen relative to a 
previous point in time.  In addition, providing omalizumab to all patients in this study 
provides larger sample sizes for analyses such as durability of response, relative to 
designs such as a randomizationwithdrawal approach.  Moreover, this open-label 
design will allow an examination of the impact of longer treatment duration on durability 
of response, as discussed in Section 6.5.3.1.
4.
MATERIALS AND METHODS
4.1
PATIENTS
The study will enroll patients from the double-blind, placebo-controlled, Phase III 
Study GA39688/GA39855 who have completed study treatment. These patients may 
enroll in this open-label study at the Week 24 visit of Study GA39688 or GA39855, or 
within 7 calendar days after the Week 24 visit (see Section 3.1 for further explanation).  
Patients must complete the Week 24 visit (and the assessments at this visit) of either 
Study GA39688 or Study GA39855 in order to be eligible to enroll into this study. 
4.1.1
Inclusion Criteria
Patients must meet the following criteria for study entry:

Signed Informed Consent Form

Age 1875 years old, inclusive, at time of signing informed consent form for 
Study GA39688 or Study GA39855

Ability to comply with the study protocol, in the investigator's judgment

Participation in Study GA39688 or Study GA39855, including completion of 
endoscopy and other assessments at Week 24, without discontinuation of study 
drug

Completion of eDiary daily assessments for at least 4 out of 7 days in the week prior 
to the Week 24 visit of Study GA39688 or Study GA39855

For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use acceptable contraceptive methods during the 
treatment period and for 60 days after the last dose of study drug
–
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle 
of the patient.  Periodic abstinence (e.g., calendar, ovulation, symptothermal, or 
postovulation methods) and withdrawal are not acceptable methods of 
contraception.
–
Acceptable methods of contraception include surgical sterilization (e.g., bilateral 
tubal ligation, vasectomized partner), hormonal contraception (e.g., implantable,
injectable, patch, oral), and intrauterine device (IUD).

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–
Women of childbearing potential must have a negative pregnancy test result 
prior to initiation of study drug in this study.
4.1.2
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:

Anaphylaxis/hypersensitivity related to study drug in Study GA39688/GA39855

Serious adverse events related to study drug in Study GA39688/GA39855 that the 
investigator or Sponsor determines may jeopardize the patient's safety if he or she 
continues in the study

Uncontrolled epistaxis within Study GA39688 or GA39855

Pregnant or breastfeeding, or intending to become pregnant during the study or 
within 60 days after the last dose of omalizumab

Any serious medical condition or abnormality in clinical laboratory tests that, in the 
investigator's judgment, precludes the patient's safe participation in and completion 
of the study
4.1.3
Omalizumab Dose Determination
Serum total IgE levels and body weight from the screening data from 
Study GA39688/GA39855 will be used to determine patient's eligibility for the study and 
determination of omalizumab dose. The serum total IgE levels and body weight should 
be based on the values from Day -35 of Study GA39688/GA39855 unless values from 
alternate timepoints during the screening period of those studies were utilized for the 
determination of study drug dosing in Study GA39688/GA39855 (e.g., because of 
missing values at Day -35).
4.2
METHOD OF TREATMENT ASSIGNMENT AND BLINDING
As this is an open-label study, all patients will receive omalizumab. To maintain the 
blind to the treatment assignment of the previous Study GA39688/GA39855, there will 
be no adjustment in dosing from those doses assigned in Study GA39688/GA39855,
which are based on values of total IgE and body weight from the screening period of 
Study GA39688/GA39855.
To minimize bias in this study, patients and the evaluating physicians will be blinded to 
treatment assignment of the previous Study GA39688/GA39855 until all patients have 
either completed the study through the follow-up period (Week 76) or discontinued early 
from the study, the database is locked, and the study analyses are final.
4.3
STUDY TREATMENT AND OTHER TREATMENTS RELEVANT 
TO THE STUDY DESIGN
The investigational medicinal product (IMP) for this study is omalizumab.

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4.3.1
Study Treatment Formulation, Packaging, and Handling
4.3.1.1
Omalizumab
Omalizumab will be supplied by the Sponsor.  Omalizumab is a sterile, white,
preservative-free, lyophilized powder, contained in a single-use vial that will be
reconstituted with Sterile Water for Injection (SWFI), USP, and administered as an SC
injection.  Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose,
2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg
polysorbate 20.  Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after
reconstitution with 1.4 mL SWFI, USP.  For additional details, see the pharmacy manual 
and the Omalizumab Investigator's Brochure.
4.3.1.2
Mometasone Furoate Monohydrate Nasal Spray
In this study, mometasone furoate monohydrate nasal spray is considered a non-IMP
and is used as background therapy only.
Each spray delivers 50 g of mometasone furoate monohydrate per actuation.  Sites are 
responsible for ensuring patients have access to the required mometasone furoate 
monohydrate nasal spray.  The nasal spray should be stored appropriately as per the 
local prescribing information. 
Any adverse events associated with an overdose or incorrect administration of 
mometasone furoate monohydrate nasal spray should be recorded on the 
Adverse Event electronic Case Report Form (eCRF).  
4.3.2
Study Treatment Dosage, Administration, and Compliance
The treatment regimen is summarized in Section 3.1.
Any overdose or incorrect administration of omalizumab should be noted on the 
Study Drug Administration eCRF.  Adverse events associated with an overdose or 
incorrect administration of any of the study treatments should be recorded on the 
Adverse Event eCRF.
Guidelines for dosage modification and treatment interruption or discontinuation for 
patients who experience adverse events are provided in Section 5.1.4.
Study drug (omalizumab) will be administered subcutaneously to patients using a 
disposable 25-gauge needle in the deltoid region of the right or left arm.  Alternatively, 
the injections can be administered in the thigh, if medically significant reasons preclude 
administration in the deltoid region.
Patients should be observed after administration of omalizumab for signs and symptoms 
of anaphylaxis.  More details are provided in Section 5.1.3.1.  In addition, the study staff 
should be prepared to manage anaphylaxis. Patients should also be informed of the 

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signs and symptoms of anaphylaxis and be instructed to seek immediate care should 
symptoms occur.
Omalizumab will be administered subcutaneously every 2 or 4 weeks.  Because the 
solution is slightly viscous, the injection may take 510 seconds to administer.  The 
dose (mg) and dosing frequency will be determined by serum total IgE level (IU/mL) 
(measured via central laboratory) and body weight (kg) as specified in Appendix 2.  
Both IgE level and body weight used for dosing will be based on values obtained during 
the screening period of Study GA39688/GA39855 as per Section 4.1.3.  Assignment of 
omalizumab dose will be determined by using the dosing table in Appendix 2.  Doses of 
150 mg are divided among more than one injection site to limit injections to no more 
than 150 mg per site.  The reconstituted vial is to be used for single-dose administration 
only.
Study drug kits must be stored at 2C8C (36F46F) in refrigerated conditions in a 
limited access area and/or a locked refrigerator.  Study drug should not be frozen or 
shaken.  Study drug should be stored immediately upon receipt but no later than 
24 hours after receipt. Omalizumab is for single-use only and contains no preservatives.  
The solution may be used for SC administration within 8 hours following reconstitution if 
stored in the vial at 2C8C (36F46F) or within 4 hours of reconstitution if stored at
room temperature.  For further details on drug handling, see the pharmacy manual.
4.3.3
Mometasone Furoate Monohydrate Nasal Spray
All patients will be required to continue mometasone furoate nasal spray 
(e.g., Nasonex), as taken during Study GA39688/GA39855, throughout the duration of 
the study period, including the follow-up period from Week 52 through Week 76.  As in 
Study GA39688/GA39855, patients will take two sprays/nostril, both nostrils, 50 g/spray
BID for a total daily dose of 400 g.  Patients deemed by the investigator to be intolerant 
to a BID regimen of mometasone may be treated with a stable dosage of mometasone 
QD (two sprays/nostril, both nostrils, 50 g/spray QD for a total daily dosage of 200 g).  
Any patient transitioned to daily mometasone should remain on this regimen for the 
remainder of this OLE study. 
Patient adherence to prescribed mometasone regimen will be assessed by the 
investigator at clinic visits and recorded in the appropriate eCRF.
For more information on formulation, dosing, and product safety, see the local
prescribing information for mometasone furoate nasal spray.
4.3.4
Investigational Medicinal Product Accountability
The IMP (omalizumab) required for completion of this study will be provided by the 
Sponsor.  The study site will acknowledge receipt of the IMP supplied by the sponsor 
using the interactive web-based response system (IWRS) to confirm the shipment 
condition and content.  Any damaged shipments will be replaced.

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IMPs will either be disposed of at the study site according to the study site's institutional 
standard operating procedure or be returned to the Sponsor with the appropriate 
documentation.  The site's method of destroying Sponsor-supplied IMPs must be agreed 
to by the Sponsor.  The site must obtain written authorization from the Sponsor before 
any Sponsor-supplied IMP is destroyed, and IMP destruction must be documented on 
the appropriate form.
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of by 
the study site should be recorded on the Drug Inventory Log.
4.3.5
Continued Access to Omalizumab
Currently, the Sponsor does not have any plans to provide the Roche IMP omalizumab
or any other study treatments or interventions to patients who have completed the study.  
The Sponsor may evaluate whether to continue providing omalizumab in accordance 
with the Roche Global Policy on Continued Access to Investigational Medicinal Product, 
available at the following web site:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
4.4
CONCOMITANT THERAPY
Concomitant therapy consists of any medication (e.g., prescription drugs, 
over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional 
supplements) used by a patient in addition to protocol-mandated treatment from Day -35 
(1st screening visit). All such medications should be reported to the investigator and 
recorded on the Concomitant Medications eCRF.
4.4.1
Prohibited Therapy
Use of the following concomitant therapies is prohibited as described below:

Investigational therapy other than the study drug

Sino-nasal surgical procedures, including polypectomies
Patients requiring sino-nasal surgery (e.g., nasal polypectomy) during the study 
should have their reasons for surgery documented and reviewed by the Medical 
Monitor.  Should surgery occur during the treatment phase, study medication 
should be discontinued, although study assessments should continue.  Should 
the patient elect to withdraw from study medication, the safety follow-up visits 
should be scheduled.  Details of the surgical procedure should be recorded on
the eCRF.

Any intranasal corticosteroids other than that required by the protocol

Any parenteral steroid injections such as triamcinolone

Use of verapamil

Use of cyclosporine, methotrexate, azathioprine, or mycophenolate and chronic use 
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Acute courses of oral or systemic corticosteroids must be justified and reasons 
documented.

Changes in allergen immunotherapy or initiation of new allergen immunotherapy

Changes in aspirin desensitization therapy or initiation of new aspirin desensitization 
therapy 

Use of systemic antibiotics for 14 days

Intranasal medication that may interfere with the symptoms of diseases
(antihistamines, nasal atropine, ipratropium bromide, nasal cromolyn, intranasal 
antibiotics like mupirocin irrigation), except nasal saline

Nasal decongestants except when administered by study personnel on the day of 
endoscopy immediately prior to such endoscopy
4.5
STUDY ASSESSMENTS 
The schedule of activities to be performed during the study is provided in Appendix 1.  
All activities must be performed and documented for each patient.  To ensure 
PRO instrument validity and that data standards meet health authority requirements, the 
questionnaires that will be completed at certain site visits (e.g., Sino-Nasal Outcome 
Test-22 [SNOT-22], EuroQol 5 Dimension, 5-Level Questionnaire [EQ-5D-5L], University 
of Pennsylvania Smell Identification Test [UPSIT], Asthma Quality of Life Questionnaire 
[AQLQ; for patients with comorbid asthma only], Medical Outcomes Study [MOS] Sleep 
Scale, Healthy Days Core Module) must be administered before the patient receives any 
information on disease status, prior to the performance of non-PRO assessments and 
prior to the administration of study treatment, unless otherwise specified.
Patients will be closely monitored for safety and tolerability throughout the study.  
Patients should be assessed for toxicity prior to each dose; dosing will occur only if the 
clinical assessment and laboratory test values are acceptable.
4.5.1
Informed Consent Forms and Screening Log
Written informed consent for participation in the study must be obtained before 
performing any study-related procedures.  Informed consent forms for enrolled patients 
and for patients who are not subsequently enrolled will be maintained at the study site.
All screening evaluations must be completed and reviewed to confirm that patients meet 
all eligibility criteria before enrollment.  The investigator will maintain a screening log to 
record details of all patients screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
4.5.2
Physical Examinations
Limited, symptom-directed physical examinations should be performed at specified visits 
and as clinically indicated.  Changes from baseline abnormalities should be recorded in 
patient notes.  New or worsened clinically significant abnormalities should be recorded 
as adverse events on the Adverse Event eCRF.

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4.5.3
Vital Signs
Vital signs will include measurements of pulse rate and systolic and diastolic blood 
pressure while the patient is in a seated position.  Blood pressure and pulse rate should 
be assessed prior to all study drug administrations.
4.5.4
CRSwNP Specific Assessments
The following measures of CRSwNP will be collected during the study:

NPS will be assessed by video nasal endoscopy (04 scale on each side).  Nasal 
endoscopy (including use of decongestants before the procedure) will be performed 
after all other efficacy assessments have been completed for each visit. In cases 
where nasal endoscopy is performed at a different location than the primary 
Principal Investigator site, endoscopy can be performed subsequent to the main site 
visit (within 3 days).  Standardized video files will be uploaded by the investigator or 
the assigned nasal endoscopist to the central reader's secured Internet site (see 
Appendix 3 for nasal polyp scoring system and the nasal endoscopy site manual for 
more details).  

Nasal symptoms including NCS (see Section 4.5.7.1 and Appendix 4)

SNOT-22 (see Section 4.5.7.2 and Appendix 6)

UPSIT (see Section 4.5.7.4)

Patient Global Impression of Change (PGIC) (see Section 4.5.7.3 and Appendix 7)
4.5.5
Physician Review of eDiary Data and Compliance
Electronic data from the eDiary will be transferred to a web-based platform for review.
Study site personnel (e.g., investigator) should review eDiary adherence to completion of 
eDiary at least once every 4 weeks, including during the follow-up period. Patients with 
poor eDiary adherence should be reminded during their clinic or telephone interviews 
about the importance of completing these assessments.
4.5.6
Laboratory, Biomarker, and Other Biological Samples
Samples for the following laboratory tests will be sent to the study site's local laboratory 
for analysis:

Urine pregnancy test
–
All women of childbearing potential should have a urine pregnancy test prior to 
the initiation of study drug, every 4 weeks during the study treatment period, 
and during the follow-up period, as indicated in Appendix 1.  Urine pregnancy 
test results must be reviewed and confirmed to be negative before
administering study drug in this study.  If a urine pregnancy test is positive or 
borderline, it must be confirmed by a serum pregnancy test (analyzed at the 
central laboratory) before giving study drug.

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Samples for the following laboratory tests will be sent to one or several central 
laboratories for analysis.

Standard hematology, including but not limited to:  WBC count, RBC count, 
hemoglobin, hematocrit, platelet count, differential count (neutrophils, eosinophils, 
basophils, monocytes, lymphocytes, other cells)

Standard chemistry panel (serum or plasma), including but not limited to: sodium, 
potassium, chloride, bicarbonate, glucose, BUN/urea, creatinine, total protein, 
albumin, phosphorus, calcium, total and direct bilirubin, ALP, ALT, AST, uric acid, 
LDH
Samples for the following laboratory tests will be sent to the sponsor or a designee for 
analysis:

Serum samples for pharmacokinetic (PK) and anti-drug antibody (ADA) analysis.  
PK samples may also be used for additional drug level/ADA testing.  During the 
open-label treatment period, the PK and ADA samples need to be drawn before 
administration of omalizumab.

Serum samples for determination of trough serum free-IgE and serum total-IgE.  
The IgE samples may also be used for specific IgE testing, including but not limited 
to specific IgE to Staphylococcus aureus enterotoxin.  The samples from PK, ADA,
and IgE testing will be destroyed no later than 5 years after the final Clinical Study 
Report has been completed, unless the patient gives specific consent for his or her 
residual samples to be donated for optional exploratory research.  During the 
open-label treatment period, the samples need to be drawn before administration of 
omalizumab.
4.5.7
Patient-Reported Outcomes
PRO questionnaires will be translated into the local language as appropriate and will be 
completed in their entirety at specified timepoints during the study, as outlined in
Appendix 1.  To ensure instrument validity and that data standards meet health authority 
requirements, questionnaires will be self-administered early in the clinic visit, before the 
patient receives any information on his or her disease status and prior to the 
performance of non-PRO assessments (e.g., endoscopy, UPSIT), unless otherwise 
specified.  Additionally, PROs should be collected prior to the administration of study 
treatment.
Patients will complete specific PRO assessments on a daily basis in the morning.  
For such daily PRO assessments, patients will use an eDiary.  Patients will be instructed 
to complete the questions in their eDiary in the morning, within approximately 1 hour of 
awakening.  The device will be programmed to lock data entry in the afternoon.  The 
electronic device and/or instructions for completing the questionnaires electronically will 
be provided by site staff.  During the treatment and follow-up periods, nasal symptoms 
will also be collected via interview at site visits and entered into the electronic data 
capture (EDC) system. The data will be transmitted to a centralized database 

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maintained by the electronic device vendor.  The data will be available for access by 
appropriate study personnel.
4.5.7.1
Nasal Symptoms, including Nasal Congestion Score 
Patient-reported nasal symptoms (nasal congestion, sense of smell, anterior rhinorrhea, 
posterior rhinorrhea) will be scored as not at all, mild, moderate, or severe (scores of 0, 
1, 2, or 3, respectively).  Total nasal symptom score (TNSS) consists of nasal 
congestion, loss of smell, and rhinorrhea.  Symptoms will be reported by patients daily 
(in the morning) on an eDiary, through treatment and follow-up periods. The nasal 
symptom questions, which include NCS, are provided in Appendix 4.  
Additionally, during specific visits, as indicated in Appendix 1, these patient-reported 
nasal symptoms will also be collected by site staff in clinic or by telephone, via interview
with a 1-week recall period. The interview nasal symptom assessment questions are 
provided in Appendix 5.
4.5.7.2
Sino-Nasal Outcome Test-22
SNOT-22 (Hopkins et al. 2009) utilizes a 2-week recall period to measure common 
symptoms of CRS with and without nasal polyps (nasal blockage, facial pain, sense of 
smell, drainage, need to blow nose, sneezing, runny nose, and sleep and emotional 
issues; see Appendix 6).
The 22 items are summed to provide a total score, with a lower score indicating fewer 
problems and better HRQoL.  The SNOT-22 will be completed electronically at specified 
timepoints, as outlined in the schedule of activities (see Appendix 1).
4.5.7.3
Patient Global Impression of Change
The PGIC is a single-item assessment of the patient's impression of his or her change in 
nasal polyp symptoms since the previous study visit. Change in nasal polyps symptoms 
is rated on a seven-point scale ranging from very much worse to very much improved. 
The PGIC will be administered at specific visits specified in the schedule of activities
(see Appendix 1).  A copy of the PGIC is provided in Appendix 7.
4.5.7.4
University of Pennsylvania Smell Identification Test
The UPSIT (Doty et al. 1984) is a 40-item objective assessment of sense of olfactory 
function. It is a self-administered "scratch-and-sniff" test.  The UPSIT is provided in 
booklets that have 40 microencapsulated odorants, each with a multiple-choice option 
for the response. The number of correct responses is summed to provide a total score. 
The UPSIT will be completed at clinic visits at specified timepoints, as outlined in the 
schedule of activities (see Appendix 1).
4.5.7.5
Asthma Quality of Life Questionnaire (Patients with Comorbid 
Asthma Only)
The standardized AQLQ (AQLQ[S]) will be completed by patients with comorbid asthma 
in order to assess the patients' asthma-specific HRQoL (Juniper et al. 1999).  The

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32-item questionnaire contains four domains:  activity limitations, symptoms, emotional 
function, and environmental stimuli.  The AQLQ(S) has a recall specification of 2 weeks.  
Items are scored on a seven-point scale ranging from 1 (severe impairment) to 7 
(no impairment).  A copy of the AQLQ(S) is provided in Appendix 8.  
4.5.7.6
EuroQol 5-Dimension 5-Level Questionnaire
The EQ-5D-5L is a self-reported health status questionnaire that consists of 
six questions that are used to calculate a health utility score for use in health economic 
analysis (EuroQol Group 1990; Brooks 1996; Herdman et al. 2011; Janssen et al. 2013;
Appendix 9).  Patients will complete the EQ-5D-5L at specific visits as specified in the 
schedule of activities (see Appendix 1). 
There are two components to the EuroQol EQ-5D-5L:  a five-item health state profile that 
assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression 
as well as a visual analogue scale that measures health state.  Published weighting 
systems allow for creation of a single summary score.  Overall scores range from 0 to 1, 
with low scores representing a higher level of dysfunction.  The EQ-5D-5L will be utilized 
in this study for economic modeling.  
4.5.7.7
Medical Outcomes Study Sleep Scale
The MOS Sleep Scale is a 12-item questionnaire asking patients to rate various 
dimensions of their sleep over the past 4 weeks (Hays and Stewart 1992; Spritzer and 
Hays 2003). Several scores can be derived: sleep disturbance, snoring, shortness of 
breath, sleep adequacy, somnolence, Sleep Problems Index I, Sleep Problems Index II, 
sleep quantity, and optimal sleep (see Appendix 10).
4.5.7.8
Healthy Days Core Module
The Healthy Days Core Module is a four-item questionnaire that asks patients to rate 
their overall health and number of healthy days they experienced in the past month. It is 
a brief assessment of the overall physical and mental health of a patient (see
Appendix 11). Patients will complete the Healthy Days Core Module at specific visits as 
specified in the schedule of activities (see Appendix 1).
4.5.8
Optional Samples for Research Biosample Repository
4.5.8.1
Overview of the Research Biosample Repository
The Research Biosample Repository (RBR) is a centrally administered group of facilities 
used for the long-term storage of human biologic specimens, including body fluids, solid 
tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides).  The collection, 
storage, and analysis of RBR specimens will facilitate the rational design of new 
pharmaceutical agents and the development of diagnostic tests, which may allow for 
individualized drug therapy for patients in the future.

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Specimens for the RBR will be stored from patients who give specific consent to donate 
samples for research. RBR specimens will be used to achieve the following objectives:

To study the association of biomarkers with efficacy, adverse events, or disease 
progression

To increase knowledge and understanding of disease biology

To study drug response, including drug effects and the processes of drug absorption 
and disposition

To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays
4.5.8.2
Approval by the Institutional Review Board or Ethics 
Committee
Collection and submission of biological samples to the RBR is contingent upon the 
review and approval of the exploratory research and the RBR portion of the Informed 
Consent Form by each site's Institutional Review Board or Ethics Committee (IRB/EC) 
and, if applicable, an appropriate regulatory body.  If a site has not been granted 
approval for RBR sampling, this section of the protocol (Section 4.5.8) will not be 
applicable at that site.
4.5.8.3
Sample Collection
The following samples will be stored in the RBR and used for research purposes, 
including, but not limited to, research related to omalizumab or CRSwNP and related 
diseases:

Residual blood, serum, and any derivatives thereof (e.g., DNA, RNA, proteins, 
peptides), including residual PK and ADA serum
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual.  
RBR specimens are to be stored until they are no longer needed or until they are 
exhausted.  However, the RBR storage period will be in accordance with the 
IRB/EC-approved Informed Consent Form and applicable laws (e.g., health authority 
requirements).
4.5.8.4
Confidentiality
Specimens and associated data will be labeled with a unique patient identification 
number.
Patient medical information associated with RBR specimens is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law.

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Given the complexity and exploratory nature of the analyses of RBR specimens, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication.
Data generated from RBR specimens must be available for inspection upon request by 
representatives of national and local health authorities, and Sponsor monitors, 
representatives, and collaborators, as appropriate.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR data will become and remain the exclusive and unburdened property 
of the Sponsor, except where agreed otherwise.
4.5.8.5
Consent to Participate in the Research Biosample Repository
The Informed Consent Form will contain a separate section that addresses participation 
in the RBR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RBR.  Patients will be 
told that they are free to refuse to participate and may withdraw their specimens at any 
time and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to provide optional RBR specimens.  
Patients who decline to participate will not provide a separate signature.
The investigator should document whether or not the patient has given consent to 
participate and (if applicable) the date(s) of consent, by completing the RBR Research 
Sample Informed Consent eCRF.
In the event of an RBR participant's death or loss of competence, the participant's 
specimens and data will continue to be used as part of the RBR research.
4.5.8.6
Withdrawal from the Research Biosample Repository
Patients who give consent to provide RBR specimens have the right to withdraw their 
consent from the RBR at any time for any reason.  However, if RBR specimens have 
been tested prior to withdrawal of consent, results from those tests will remain as part of 
the overall research data.  If a patient wishes to withdraw consent to the testing of his or 
her specimens, the investigator must inform the Medical Monitor in writing of the 
patient's wishes through use of the appropriate RBR Subject Withdrawal Form and, if the 
trial is ongoing, must enter the date of withdrawal on the RBR Research Sample 
Withdrawal of Informed Consent eCRF.  The patient will be provided with instructions on 
how to withdraw consent after the trial is closed.  A patient's withdrawal from 
Study WA40169 does not, by itself, constitute withdrawal of specimens from the RBR.  
Likewise, a patient's withdrawal from the RBR does not constitute withdrawal from
Study WA40169.

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4.5.8.7
Monitoring and Oversight
RBR specimens will be tracked in a manner consistent with Good Clinical Practice by a 
quality-controlled, auditable, and appropriately validated laboratory information 
management system, to ensure compliance with data confidentiality as well as 
adherence to authorized use of specimens as specified in this protocol and in the 
Informed Consent Form.  Sponsor monitors and auditors will have direct access to 
appropriate parts of records relating to patient participation in the RBR for the purposes 
of verifying the data provided to the Sponsor.  The site will permit monitoring, audits, 
IRB/EC review, and health authority inspections by providing direct access to source 
data and documents related to the RBR samples.
4.6
TREATMENT, PATIENT, STUDY, AND SITE DISCONTINUATION
4.6.1
Study Treatment Discontinuation
Patients must permanently discontinue study treatment if they experience any of the 
following:

Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient's safety if he or she continues to receive study treatment

Investigator or Sponsor determines it is in the best interest of the patient

Pregnancy
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF.  Patients who discontinue study treatment will not be replaced.  
Patients who discontinue study treatment should continue with remaining study 
assessments as per Appendix 1.
Patients who do not wish to continue with study assessments will return to the clinic for a 
dosing termination visit within 28 days after the last dose of study drug and will then 
subsequently return for a safety follow-up visit (see Appendix 1 for additional details).  
4.6.2
Patient Discontinuation from Study
Patients have the right to voluntarily withdraw from the study at any time for any reason.  
In addition, the investigator has the right to withdraw a patient from the study at any time.  
Reasons for withdrawal from the study may include, but are not limited to, the following:

Patient withdrawal of consent

Study termination or site closure

Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient's safety if he or she continues in the study

Investigator or Sponsor determines it is in the best interest of the patient
Every effort should be made to obtain information on patients who discontinue from the 
study. The patient should be asked to return for a study discontinuation visit within 

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28 days after the last dose of study drug and then return for a safety follow-up visit.  The 
primary reason for withdrawal from the study should be documented on the appropriate 
eCRF.  If a patient requests to be withdrawn from the study, this request must be 
documented in the source documents and signed by the investigator.  Patients who 
withdraw from the study will not be replaced.
4.6.3
Study Discontinuation
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include, but are not limited to, the following:

The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to patients

Patient enrollment is unsatisfactory
The Sponsor will notify the investigator if the Sponsor decides to discontinue the study.  
4.6.4
Site Discontinuation
The Sponsor has the right to close a site at any time.  Reasons for closing a site may 
include, but are not limited to, the following:

Excessively slow recruitment

Poor protocol adherence

Inaccurate or incomplete data recording

Non-compliance with the International Council for Harmonisation (ICH) guideline for 
Good Clinical Practice

No study activity (i.e., all patients have completed the study and all obligations have 
been fulfilled)
5.
ASSESSMENT OF SAFETY
Omalizumab is not approved for the treatment of adult patients with CRSwNP who have 
had an inadequate response to standard-of-care treatments.  The safety plan for 
patients in this study is based on the extensive clinical and postmarketing experience 
with omalizumab for the last 13 years.  Omalizumab is marketed in over 90 countries for 
allergic asthma and 80 countries for CIU/CSU as of 31 December 2016.  The estimated 
cumulative omalizumab exposure is 31,000 Patient-Years in clinical trials and 
819,000 Patient-Years in the postmarketing setting as of 31 December 2016.
The clinical safety of omalizumab has been well documented in a number of clinical trials 
that involve adults and children with moderate to severe allergic asthma.  The adverse 
event profile of omalizumab observed during the clinical development program of allergic 
asthma was similar to placebo, with the most commonly reported adverse events being 
headaches and injection site reactions, including injection site pain, swelling, erythema, 
pruritus.  Anaphylactic reactions were observed but were rare and typically occurred 
within 2 hours of the first injection.  The overall adverse event profile in CIU/CSU studies 

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was consistent with the known safety profile of omalizumab. Omalizumab has also been 
investigated in patients with seasonal allergic rhinitis, perennial allergic rhinitis, atopic 
dermatitis, and peanut allergy.  The safety profile of omalizumab in non-asthma trials 
has not differed from the safety profile of omalizumab in asthma trials. 
The Sponsor does not anticipate a difference in the safety profile of omalizumab in the 
population with nasal polyps from the existing safety profile in asthma and CIU/CSU
where the safety profile of the molecule is already well defined.  No specific safety 
concerns were identified in the published literature for the similar indication and study 
population with omalizumab.
5.1
SAFETY PLAN
The anticipated important safety risks for omalizumab are outlined below.  Please refer 
to the omalizumab Investigator's Brochure for a complete summary of safety information. 
Several measures will be taken to ensure the safety of patients participating in this study.  
Eligibility criteria have been designed to exclude patients at higher risk for toxicities.  
Patients will undergo safety monitoring during the study, including assessment of the 
nature, frequency, and severity of adverse events.  In addition, guidelines for managing 
adverse events, including criteria for treatment interruption or discontinuation, is 
provided appropriately (see Section 4.6).
5.1.1
Safety and Data Monitoring
All safety events will be closely monitored by the study team.  The sponsor followed the 
U.S. FDA guidance (FDA 2006) to evaluate the need for an independent Data 
Monitoring Committee (iDMC) and decided not to have an iDMC for this study based on 
the criteria mentioned in the guidance.  Given the established safety record of 
omalizumab, the nature of nasal polyposis, and the outcomes being examined, an iDMC 
is not indicated in this study.
5.1.2
Anaphylaxis Adjudication Committee
All potential anaphylaxis cases reported by investigators to the Sponsor will be 
subsequently submitted for adjudication to a blinded three-member anaphylaxis 
adjudication committee composed of external experts in allergic diseases.  The 
committee will assess whether the reported event is a true anaphylaxis event (based on 
Sampson's criteria; see Appendix 12) and whether the reported anaphylaxis event is 
causally related to study drug.  Further details will be provided in the Anaphylaxis 
Adjudication Charter.
5.1.3
Risks Associated with Omalizumab
5.1.3.1
Anaphylaxis
Anaphylaxis has been reported to occur after administration of omalizumab in clinical 
trials and in postmarketing spontaneous reports. Anaphylactic reactions were rare in 
clinical trials (0.1%) and estimated as 0.2% from postmarketing reporting. The reported 

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signs and symptoms included, but were not limited to, bronchospasm, hypotension, 
syncope, urticaria, and/or angioedema of the throat or tongue. Some of these events 
have been reported as life threatening.
The majority of anaphylactic-type reactions have been reported to occur after the 
first dose, with numbers decreasing with subsequent doses, but such reactions were 
also reported beyond 1 year after starting scheduled treatment. The events were 
reported to occur predominantly within the first 2 hours post-dose, with few reports 
occurring as far as 36 hours post-dose.
Details regarding management of these events are provided below:

Administer omalizumab only in a healthcare setting by healthcare providers 
prepared to manage anaphylaxis that can be life-threatening; medications for the 
treatment of anaphylactic reactions should be available for immediate use following 
administration of omalizumab.

Patients should be observed for at least 2 hours after the first 3 study drug doses, 
within this OLE study, and at least 30 minutes after subsequent doses.  However, 
some patients may require longer observation periods, depending on investigator 
judgment taking into account the time to onset of anaphylaxis seen in clinical trials 
and postmarketing spontaneous reports.  The American College of Allergy, Asthma, 
and Immunology guideline on the observation period after omalizumab 
administration (Kim et al. 2010) recommends 2 hours of monitoring in the clinic after 
the first three injections and 30 minutes or an appropriate time agreed upon by the 
individual patient and healthcare professional for subsequent injections.  However, a 
delayed onset of symptoms and protracted progression of anaphylaxis should be 
taken into account when administering omalizumab (Limb et al. 2007).  

Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek 
immediate medical care should signs or symptoms occur.

Discontinue omalizumab in patients who experience a severe hypersensitivity
(anaphylactic) reaction.
5.1.3.2
Serum Sickness
Serum sickness and serum sicknesslike reactions, which are delayed allergic type III
reactions, have rarely been seen in patients treated with humanized monoclonal 
antibodies including omalizumab in the post-approval use. The onset has typically been 
15 days after administration of the first or subsequent injections, also after long 
duration of treatment. Symptoms suggestive of serum sickness include 
arthritis/arthralgia, rash (urticaria or other forms), fever, and lymphadenopathy. 
Antihistamines and corticosteroids may be useful for preventing or treating this disorder.

Patients should be informed and advised to report any suspected symptoms of 
serum sicknesslike reactions.

Physicians should stop omalizumab if a patient develops this constellation of signs 
and symptoms.

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5.1.3.3
Churg-Strauss Syndrome and Hypereosinophilic Syndrome 
Patients with severe asthma may rarely present systemic hypereosinophilic syndrome or 
allergic eosinophilic granulomatous vasculitis (Churg-Strauss syndrome), both of which 
are usually treated with systemic corticosteroids.  In rare cases, patients on therapy with 
anti-asthma medicinal products, including omalizumab, may present or develop systemic 
eosinophilia and vasculitis. These events are commonly associated with the reduction of 
oral corticosteroid therapy and alerted to the development of marked eosinophilia, 
vasculitic rash, worsening pulmonary symptoms, paranasal sinus abnormalities, 
cardiac complications, and/or neuropathy. 
Abrupt discontinuation of systemic or inhaled corticosteroids after initiation of 
omalizumab therapy is not recommended. Decreases in corticosteroids should be 
performed under the direct supervision of a physician and may need to be performed 
gradually.  Patients with known or suspected Churg-Strauss syndrome should be 
excluded from the study.
5.1.3.4
Thrombocytopenia 
In nonclinical studies, a dose-dependent and reversible circulating platelet reduction was 
observed.  In clinical studies, few patients experienced platelet counts below the lower 
limit of the normal laboratory range.  None of these changes was associated with 
bleeding episodes or a decrease in hemoglobin.  
5.1.3.5
Malignancies
During initial clinical trials in adults and adolescents 12 years of age and older with 
allergic asthma, there was a numerical imbalance in cancers arising in the active 
treatment group compared with the control group. The number of observed cases was 
uncommon (1/100) in both the active and the control group. In a subsequent 
observational study (EXCELS) comparing 5007 omalizumab-treated patients and 
2829 non-omalizumab-treated patients followed for up to 5 years, the incidence rates of 
primary malignancies per 1000 patient years were 16.01 (295/18,426 patient years) and 
19.07 (190/9963 patient years), respectively, which does not indicate an increased 
malignancy risk (rate ratio 0.84, 95% CI: 0.621.13). In a further analysis of randomized 
double-blind placebo-controlled clinical trials, including 4254 patients on omalizumab 
and 3178 patients on placebo, omalizumab treatment was not associated with an 
increased malignancy risk based on incidence rates per 1000 patient years of 4.14 
(14/3382 patient years) for omalizumab-treated patients and 4.45 (11/2474 patient years) 
for placebo patients (rate ratio 0.93, 95% CI: 0.392.27). The overall observed 
incidence rate of malignancy in the omalizumab clinical trial program was comparable to 
that reported in the general population. There were no cases of malignancy in clinical 
trials in allergic asthma in the 6 to 12 years-of-age group with omalizumab; there were 
2 cases of malignancy in the control group (medulloblastoma and nephroblastoma).
In the Phase III CIU/CSU program (733 patients enrolled and receiving at least 1 dose of 
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24 weeks), there was 1 case of malignancy in the placebo group (242 patients) and 
1 case in the omalizumab 300-mg group (412 patients) in a patient with a preexisting 
history.
5.1.3.6
Arterial Thrombotic Events
In controlled clinical trials in allergic asthma and during interim analyses of EXCELS (an
observational study), a numerical imbalance of arterial thrombotic events (ATEs) was 
observed. ATEs included stroke, transient ischemic attack, myocardial infarction, 
unstable angina, and cardiovascular death (including death from unknown cause). 
The results from EXCELS revealed the rate of ATEs per 1,000 patient years was 
7.52 (115/15,286 patient years) for omalizumab-treated patients and 5.12 
(51/9,963 patient years) for control patients. Although there was no consistent evidence 
of an association between omalizumab use and risk of ATEs, the 95% CIs were wide 
and could not definitively exclude an elevated risk.
5.1.3.7
Antibody Formation to Omalizumab
Omalizumab is a humanized monoclonal anti-IgE antibody. The formation of 
anti-omalizumab antibodies (also called ADAs) after omalizumab administration is a rare 
event.  There were 3 ADA-positive cases out of 23,375 serum samples tested in the 
Allergic Asthma and CSU/CIU programs following omalizumab administration.  These 
cases were not associated with any severe adverse events.
There was no case of drug-induced ADAs recorded across the entire CSU/CIU 
development program.
5.1.4
Management of Patients Who Experience Specific Adverse 
Events
5.1.4.1
Dose Modifications and Treatment Interruption
No dose modification or treatment interruption is allowed during the conduct of the study.  
Omalizumab should be discontinued in patients who experience a severe 
hypersensitivity reaction.
5.1.4.2
Management of Drug Induced Liver Injuries
Liver injury has not been described as a risk associated with omalizumab. However, 1) if 
the patient's AST or ALT is 8upper limit of normal (ULN), or 2) if the patient's AST or 
ALT 3ULN and total bilirubin 2ULN or clinical jaundice occurs, study drug should 
be discontinued, liver test should be repeated, and an evaluation for causes for the liver 
test abnormality should be initiated.
5.2
SAFETY PARAMETERS AND DEFINITIONS
Safety assessments will consist of monitoring and recording adverse events (including 
serious adverse events and adverse events of special interest), performing 
protocol-specified safety laboratory assessments, measuring protocol-specified vital 

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signs, and conducting other protocol-specified tests that are deemed critical to the safety 
evaluation of the study.
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.2.2.
5.2.1
Adverse Events
According to the ICH guideline for Good Clinical Practice, an adverse event is any 
untoward medical occurrence in a clinical investigation subject administered a 
pharmaceutical product, regardless of causal attribution.  An adverse event can 
therefore be any of the following:

Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product

Any new disease or exacerbation of an existing disease (a worsening in the 
character, frequency, or severity of a known condition), except as described in 
Section 5.3.5.11. 

Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline

Any deterioration in a laboratory value or other clinical test (e.g., ECG, X-ray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study drug

Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to assignment of study treatment (e.g., nasal endoscopy)
5.2.2
Serious Adverse Events (Immediately Reportable to the 
Sponsor)
A serious adverse event is any adverse event that meets any of the following criteria:

Is fatal (i.e., the adverse event actually causes or leads to death)

Is life threatening (i.e., the adverse event, in the view of the investigator, places the 
patient at immediate risk of death)
This does not include any adverse event that, had it occurred in a more severe 
form or was allowed to continue, might have caused death.

Requires or prolongs inpatient hospitalization (see Section 5.3.5.12)

Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient's ability to conduct normal life 
functions)

Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug

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
Is a significant medical event in the investigator's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above)
The terms "severe" and "serious" are not synonymous.  Severity refers to the intensity of 
an adverse event (e.g., rated as mild, moderate, or severe, or according to National 
Cancer Institute Common Terminology Criteria for Adverse Events; see Section 5.3.3); 
the event itself may be of relatively minor medical significance (such as severe 
headache without any further findings).
Severity and seriousness need to be independently assessed for each adverse event
recorded on the eCRF.
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2 for
reporting instructions).
5.2.3
Adverse Events of Special Interest (Immediately Reportable to 
the Sponsor)
Adverse events of special interest are required to be reported by the investigator to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5.4.2 for reporting instructions).  Adverse events of special interest for this study 
are as follows:

Suspected anaphylaxis/anaphylactoid reactions identified based on Sampson's 
criteria (see Appendix 12)

Cases of potential drug-induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by 
Hy's Law (see Section 5.3.5.8)

Suspected transmission of an infectious agent by the study drug, as defined below:
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a patient exposed to a medicinal product.  This term applies only
when a contamination of the study drug is suspected.

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5.3
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS
The investigator is responsible for ensuring that all adverse events (see Section 5.2.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.45.6.
For each adverse event recorded on the Adverse Event eCRF, the investigator will make 
an assessment of seriousness (see Section 5.2.2 for seriousness criteria), severity (see 
Section 5.3.3), and causality (see Section 5.3.4).  
5.3.1
Adverse Event Reporting Period
Investigators will seek information on adverse events at each patient contact.  All 
adverse events, whether reported by the patient or noted by study personnel, will be 
recorded in the patient's medical record and on the Adverse Event eCRF.
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention (e.g., invasive 
procedures such as biopsies, discontinuation of medications) should be reported 
(see Section 5.4.2 for instructions for reporting serious adverse events).
After initiation of study drug, all adverse events will be reported until the end of the safety 
follow-up period (Week 76).  Instructions for reporting adverse events that occur after the 
adverse event reporting period are provided in Section 5.6.
5.3.2
Eliciting Adverse Event Information
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following:
"How have you felt since your last clinic visit?"
"Have you had any new or changed health problems since you were last here?" 
5.3.3
Assessment of Severity of Adverse Events
Table 2 will be used for assessing severity of adverse events.
Table 2
Adverse Event Severity Grading Scale
Severity
Description
Mild
Discomfort noticed, but no disruption of normal daily activity
Moderate
Discomfort sufficient to reduce or affect normal daily activity
Severe
Incapacitating with inability to work or to perform normal daily activity
Note:  Regardless of severity, some events may also meet seriousness criteria.  
Refer to definition of a serious adverse event (see Section 5.2.2).

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5.3.4
Assessment of Causality of Adverse Events
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether an 
adverse event is considered to be related to the study drug, indicating "yes" or "no" 
accordingly.  The following guidance should be taken into consideration (see also 
Table 3):

Temporal relationship of event onset to the initiation of study drug

Course of the event, with special consideration of the effects of dose reduction, 
discontinuation of study drug, or reintroduction of study drug (as applicable)

Known association of the event with the study drug or with similar treatments

Known association of the event with the disease under study

Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event

Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event
Table 3
Causal Attribution Guidance
Is the adverse event suspected to be caused by the study drug on the basis of facts, evidence, 
science-based rationales, and clinical judgment?
YES
There is a plausible temporal relationship between the onset of the adverse event and 
administration of the study drug, and the adverse event cannot be readily explained by 
the patient's clinical state, intercurrent illness, or concomitant therapies; and/or the 
adverse event follows a known pattern of response to the study drug; and/or the 
adverse event abates or resolves upon discontinuation of the study drug or dose 
reduction and, if applicable, reappears upon re-challenge.
NO
An adverse event will be considered related, unless it fulfills the criteria specified below.  
Evidence exists that the adverse event has an etiology other than the study drug 
(e.g., preexisting medical condition, underlying disease, intercurrent illness, 
or concomitant medication); and/or the adverse event has no plausible temporal 
relationship to administration of the study drug (e.g., cancer diagnosed 2 days after 
first dose of study drug).
For patients receiving combination therapy, causality will be assessed individually for 
each protocol-mandated therapy.
5.3.5
Procedures for Recording Adverse Events
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF.  Avoid colloquialisms and abbreviations.
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF.

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5.3.5.1
Injection-Site Reactions
Local adverse events that occur during (or within 24 hours) after study drug 
administration and are judged to be related to study drug injection should be captured as 
a diagnosis (e.g., "injection-site reaction" on the Adverse Event eCRF).  Associated 
signs and symptoms should be recorded on the dedicated Injection-Site Reaction eCRF.  
If a patient experiences both a local and systemic reaction to the same dose of study 
drug, each reaction should be recorded separately on the Adverse Event eCRF, with 
signs and symptoms also recorded separately on the dedicated Injection-Site
Reaction eCRF.
5.3.5.2
Anaphylactic Reactions
The investigator should use Sampson's criteria (Appendix 12) to identify the potential 
cases of anaphylaxis and report as a diagnosis on the Adverse Event eCRF.  If possible, 
avoid ambiguous terms such as "systemic reaction." Any case of known or suspected 
anaphylaxis will require the completion of a dedicated eCRF to record the specific signs 
and symptoms associated with this event.  
5.3.5.3
Diagnosis versus Signs and Symptoms
A diagnosis (if known) should be recorded on the Adverse Event eCRF rather than 
individual signs and symptoms (e.g., record only liver failure or hepatitis rather than 
jaundice, asterixis, and elevated transaminases).  However, if a constellation of signs 
and/or symptoms cannot be medically characterized as a single diagnosis or syndrome 
at the time of reporting, each individual event should be recorded on the Adverse Event 
eCRF.  If a diagnosis is subsequently established, all previously reported adverse events 
based on signs and symptoms should be nullified and replaced by one adverse event 
report based on the single diagnosis, with a starting date that corresponds to the starting 
date of the first symptom of the eventual diagnosis.
5.3.5.4
Adverse Events That Are Secondary to Other Events
In general, adverse events that are secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events.  A medically significant secondary adverse event 
that is separated in time from the initiating event should be recorded as an independent 
event on the Adverse Event eCRF.  For example:

If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF.

If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF.

If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF.

If dizziness leads to a fall and consequent fracture, all three events should be 
reported separately on the eCRF.

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
If neutropenia is accompanied by an infection, both events should be reported 
separately on the eCRF.
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated.
5.3.5.5
Persistent or Recurrent Adverse Events
A persistent adverse event is one that extends continuously, without resolution, between 
patient evaluation timepoints.  Such events should only be recorded once on the 
Adverse Event eCRF.  The initial severity (intensity or grade) of the event will be 
recorded at the time the event is first reported.  If a persistent adverse event becomes 
more severe, the most extreme severity should also be recorded on the Adverse Event 
eCRF.  If the event becomes serious, it should be reported to the Sponsor immediately 
(i.e., no more than 24 hours after learning that the event became serious; see
Section 5.4.2 for reporting instructions).  The Adverse Event eCRF should be updated 
by changing the event from "non-serious" to "serious," providing the date that the event 
became serious, and completing all data fields related to serious adverse events.
A recurrent adverse event is one that resolves between patient evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as a 
separate event on the Adverse Event eCRF.
5.3.5.6
Abnormal Laboratory Values
Not every laboratory abnormality qualifies as an adverse event.  A laboratory test result 
must be reported as an adverse event if it meets any of the following criteria:

Is accompanied by clinical symptoms

Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation)

Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy

Is clinically significant in the investigator's judgment 
It is the investigator's responsibility to review all laboratory findings.  Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event.
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., ALP and bilirubin 5upper limit of normal [ULN] associated with cholestasis), only 
the diagnosis (i.e., cholestasis) should be recorded on the Adverse Event eCRF.
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating whether the test result is above or below the normal range 
(e.g., "elevated potassium," as opposed to "abnormal potassium").  If the laboratory 

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abnormality can be characterized by a precise clinical term per standard definitions, the 
clinical term should be recorded as the adverse event.  For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as "hyperkalemia."
Observations of the same clinically significant laboratory abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.3.5.5 for 
details on recording persistent adverse events).
5.3.5.7
Abnormal Vital Sign Values
Not every vital sign abnormality qualifies as an adverse event.  A vital sign result must 
be reported as an adverse event if it meets any of the following criteria:

Is accompanied by clinical symptoms

Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation)

Results in a medical intervention or a change in concomitant therapy

Is clinically significant in the investigator's judgment 
It is the investigator's responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an adverse event.
If a clinically significant vital sign abnormality is a sign of a disease or syndrome
(e.g., high blood pressure), only the diagnosis (i.e., hypertension) should be recorded on 
the Adverse Event eCRF.
Observations of the same clinically significant vital sign abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.3.5.5 for 
details on recording persistent adverse events).
5.3.5.8
Abnormal Liver Function Tests
The finding of an elevated ALT or AST (3ULN) in combination with either an elevated 
total bilirubin (2ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury 
(as defined by Hy's Law).  Therefore, investigators must report as an adverse event the 
occurrence of either of the following:

Treatment-emergent ALT or AST 3ULN in combination with total bilirubin 
2ULN

Treatment-emergent ALT or AST 3ULN in combination with clinical jaundice
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Section 5.3.5.3) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 

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the event), either as a serious adverse event or an adverse event of special interest (see 
Section 5.4.2).
5.3.5.9
Deaths
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5.3.1), regardless of relationship to study drug, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2). 
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, "unexplained death" should be recorded on the Adverse Event eCRF.  If the 
cause of death later becomes available (e.g., after autopsy), "unexplained death" should 
be replaced by the established cause of death.  The term "sudden death" should not be 
used unless combined with the presumed cause of death (e.g., "sudden cardiac death").
Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.6.
5.3.5.10
Preexisting Medical Conditions
A preexisting medical condition is one that is present at the screening visit for this study.  
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF.
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study.  When 
recording such events on the Adverse Event eCRF, it is important to convey the concept
that the preexisting condition has changed by including applicable descriptors 
(e.g., "more frequent headaches").
5.3.5.11
Lack of Efficacy or Worsening of Nasal Polyposis
Medical occurrences or symptoms of deterioration that are anticipated as part of 
nasal polyposis should be recorded as an adverse event if judged by the investigator to 
have unexpectedly worsened in severity or frequency or changed in nature at any time 
during the study.  When recording an unanticipated worsening of nasal polyposis on the 
Adverse Event eCRF, it is important to convey the concept that the condition has 
changed by including applicable descriptors (e.g., "worsening of nasal polyposis as 
compared to baseline").
5.3.5.12
Hospitalization or Prolonged Hospitalization
Any adverse event that results in hospitalization (i.e., inpatient admission to a hospital) 
or prolonged hospitalization should be documented and reported as a serious adverse 

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event (per the definition of serious adverse event in Section 5.2.2), except as outlined 
below.  
An event that leads to hospitalization under the following circumstances should not be 
reported as an adverse event or a serious adverse event:

Hospitalization for respite care

Planned hospitalization required by the protocol if required by site (e.g., for study 
drug administration or nasal endoscopy) 

Hospitalization for a preexisting condition, provided that all of the following criteria 
are met:
The hospitalization was planned prior to the study or was scheduled during the 
study when elective surgery became necessary because of the expected 
normal progression of the disease.
The patient has not experienced an adverse event.
An event that leads to hospitalization under the following circumstances is not 
considered to be a serious adverse event, but should be reported as an adverse event 
instead:

Hospitalization that was necessary because of patient requirement for outpatient 
care outside of normal outpatient clinic operating hours
5.3.5.13
Adverse Events Associated with an Overdose or Error in Drug 
Administration
An overdose is the accidental or intentional use of a drug in an amount higher than the 
dose being studied.  An overdose or incorrect administration of study treatment is not 
itself an adverse event, but it may result in an adverse event.  All adverse events 
associated with an overdose or incorrect administration of study drug should be 
recorded on the Adverse Event eCRF.  If the associated adverse event fulfills 
seriousness criteria, the event should be reported to the Sponsor immediately 
(i.e., no more than 24 hours after learning of the event; see Section 5.4.2).
5.3.5.14
Patient-Reported Outcome Data
Adverse event reports will not be derived from PRO data by the Sponsor, and safety 
analyses will not be performed using PRO data.  However, if any PRO responses 
suggestive of a possible adverse event are identified during site review of the PRO data, 
the investigator will determine whether the criteria for an adverse event have been met 
and, if so, will report the event on the Adverse Event eCRF.
5.4
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 

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place more than 24 hours after the investigator learns of the event.  The following is a list 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study drug:

Serious adverse events (defined in Section 5.2.2; see Section 5.4.2 for details on 
reporting requirements)

Adverse events of special interest (defined in Section 5.2.3; see Section 5.4.2 for 
details on reporting requirements)

Pregnancies (see Section 5.4.3 for details on reporting requirements)
The investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the 
information).  New significant information includes the following:

New signs or symptoms or a change in the diagnosis

Significant new diagnostic test results

Change in causality based on new information

Change in the event's outcome, including recovery

Additional narrative information on the clinical course of the event
Investigators must also comply with local requirements for reporting serious adverse 
events to the local health authority and IRB/EC.
5.4.1
Emergency Medical Contacts
Medical Monitor Contact Information (Primary)
Medical Monitor:
, M.D.
PPD 
Telephone No. (24/7) North America:
(888) 483-7729
Telephone No. (24/7) Europe:
44 1223 374 240
Additional contact information will be provided by the Sponsor as needed.
Questions and issues related to medical monitoring may be directed to the above 
numbers, which are available 24 hours per day, 7 days per week.
Roche Medical Monitor Contact Information (Secondary)
Roche Medical Responsible:
, M.D.  
Telephone No.:

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5.4.2
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest
5.4.2.1
Events That Occur prior to Study Drug Initiation
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention should be reported.  
The paper Clinical Trial Serious Adverse Event/Adverse Event of Special Interest 
Reporting Form provided to investigators should be completed and submitted to the 
Sponsor or its designee immediately (i.e., no more than 24 hours after learning of the 
event), either by faxing or by scanning and emailing the form using the fax number or 
email address provided to investigators.
5.4.2.2
Events That Occur after Study Drug Initiation
After initiation of study drug, all adverse events including serious adverse events, 
non-serious events, and adverse events of special interest will be reported until 
completion of the follow-up period.  Investigators should record all case details that can 
be gathered immediately (i.e., within 24 hours after learning of the event) on the 
Adverse Event eCRF and submit the report via the EDC system.  A report will be 
generated and sent to Roche Safety Risk Management by the EDC system.
In the event that the EDC system is unavailable, the paper Clinical Trial Serious Adverse 
Event/Adverse Event of Special Interest Reporting Form provided to investigators should 
be completed and submitted to the Sponsor or its designee immediately (i.e., no more 
than 24 hours after learning of the event), either by faxing or by scanning and emailing 
the form using the fax number or email address provided to investigators.  Once the 
EDC system is available, all information will need to be entered and submitted via the 
EDC system.  
Instructions for reporting serious adverse events that occur post-study are provided in 
Section 5.6.
5.4.3
Reporting Requirements for Pregnancies
5.4.3.1
Pregnancies in Female Patients
Female patients of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study or within 60 days after the last 
dose of study drug.  A Clinical Trial Pregnancy Reporting Form should be completed and 
submitted to the Sponsor or its designee immediately (i.e., no more than 24 hours after 
learning of the pregnancy), either by faxing or by scanning and emailing the form using 
the fax number or email address provided to investigators.  Pregnancy should not be 
recorded on the Adverse Event eCRF.  The investigator should discontinue study drug 
and counsel the patient, discussing the risks of the pregnancy and the possible effects 
on the fetus.  Monitoring of the patient should continue until conclusion of the pregnancy.  
Any serious adverse events associated with the pregnancy (e.g., an event in the fetus, 
an event in the mother during or after the pregnancy, or a congenital anomaly/birth
defect in the child) should be reported on the Adverse Event eCRF.  In addition, the 

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investigator will submit a Clinical Trial Pregnancy Reporting Form when updated 
information on the course and outcome of the pregnancy becomes available.  
5.4.3.2
Abortions
Any abortion should be classified as a serious adverse event (as the Sponsor considers 
abortions to be medically significant), recorded on the Adverse Event eCRF, and 
reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event; see Section 5.4.2).  
5.4.3.3
Congenital Anomalies/Birth Defects
Any congenital anomaly/birth defect in a child born to a female patient exposed to study 
drug should be classified as a serious adverse event, recorded on the Adverse Event 
eCRF, and reported to the Sponsor immediately (i.e., no more than 24 hours after 
learning of the event; see Section 5.4.2).
5.5
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS
5.5.1
Investigator Follow-Up
The investigator should follow each adverse event until the event has resolved to baseline 
grade or better, the event is assessed as stable by the investigator, the patient is lost to 
follow-up, or the patient withdraws consent.  Every effort should be made to follow all 
serious adverse events considered to be related to study drug or trial-related procedures 
until a final outcome can be reported.
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the patient's medical record to facilitate source data 
verification.
All pregnancies reported during the study should be followed until pregnancy outcome.
5.5.2
Sponsor Follow-Up
For serious adverse events, adverse events of special interest, and pregnancies, the 
Sponsor or a designee may follow up by telephone, fax, email, and/or a monitoring visit 
to obtain additional case details and outcome information (e.g., from hospital discharge 
summaries, consultant reports, autopsy reports) in order to perform an independent 
medical assessment of the reported case.
5.6
ADVERSE EVENTS THAT OCCUR AFTER THE ADVERSE 
EVENT REPORTING PERIOD
The Sponsor should be notified if the investigator becomes aware of any serious 
adverse event that occurs after the end of the adverse event reporting period (defined as 
study completion date), if the event is believed to be related to prior study drug treatment.  
These events should be reported through use of the Adverse Event eCRF.  However, if 
the EDC system is not available, the investigator should report these events directly to 
the Sponsor or its designee, either by faxing or by scanning and emailing the paper 

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Clinical Trial Serious Adverse Event/Adverse Event of Special Interest Reporting Form 
using the fax number or email address provided to investigators.
5.7
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES
The Sponsor will promptly evaluate all serious adverse events and adverse events of 
special interest against cumulative product experience to identify and expeditiously 
communicate possible new safety findings to investigators, IRBs, ECs, and applicable 
health authorities based on applicable legislation.
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events using the following reference document:

Omalizumab Investigator's Brochure
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document.
Reporting requirements will also be based on the investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed.
6.
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN
The analysis of complete data from the study, including data from the safety follow-up 
period will be performed when all patients have either discontinued the study early or 
completed the safety follow-up period, all data from the study are in the database, and 
the database is cleaned and locked.  Detailed specifications of the statistical methods 
will be described in the Statistical Analysis Plan (SAP).  The SAP may be reviewed by 
health authorities and will be finalized prior to database lock.  To allow for incorporation 
of health authority input, the statistical methods in the SAP may differ from and will 
supersede those described in this document.
Throughout this Section the term "descriptive statistics" is defined as follows, unless 
otherwise noted: 

For continuous variables descriptive statistics will include at a minimum: number of 
subjects, mean, standard deviation, median, minimum, and maximum.

For categorical variables descriptive statistics will include at a minimum: number of 
patients and percentage of patients.
6.1
DETERMINATION OF SAMPLE SIZE
No formal sample size calculation was performed for this study because the primary 
analysis is descriptive in nature, there will be no formal hypothesis testing, and this study 
is an OLE of previous studies (Studies GA39688 and GA39855), which plan to enroll 
approximately 240 patients in total (120 patients each).  In order to be eligible for 

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enrollment into this study, the patient must complete assessments at Week 24 in the 
prior study without discontinuation of study drug.  Therefore, due to the inclusion criteria 
of this study and potential dropout from Studies GA39688 and GA39855, the sample 
size of approximately 240 patients is a maximum.
6.2
ANALYSIS COHORTS
The study population will consist of two cohorts:

Cohort A: Study participants who have completed Study GA39688 grouped 
according to treatment randomized in Study GA39688 (omalizumab or placebo) and 
who have enrolled into the current study

Cohort B: Study participants who have completed Study GA39855 grouped 
according to treatment randomized in Study GA39855 (omalizumab or placebo) and 
who have enrolled into the current study
6.3
SUMMARIES OF TREATMENT GROUP AND COHORT
COMPARABILITY
The two previous studies (GA39688 and GA39855) from which the current study 
population is drawn are planned to be identical with respect to all design considerations 
including: 

Geographic regions (North America, ex-North America)

Schedule of assessments

Inclusion/exclusion criteria

Treatment regimen based on the omalizumab dosing table (see Appendix 2) 
Therefore, baseline characteristics, study conditions, and treatment regimen 
characteristics are expected to be similar between the two trials as characterized by:

Number of injections received

Number of patients in each dosing schedule (e.g., Q2W, Q4W)

Relative dose intensity (e.g., the amount of study drug administered divided by the 
amount of study drug planned)
To ensure comparability of study treatment, Cohorts A and Cohort B baseline 
characteristics (e.g., age, sex, race/ethnicity, NPS, NCS, sense of smell, anterior 
rhinorrhea, posterior rhinorrhea, and SNOT-22) will be summarized in all patients with 
data using descriptive statistics both by cohort and by previously-randomized treatment 
group within cohort (omalizumab and placebo).  Prior study treatment characteristics will 
be compared by descriptive statistics across cohorts (e.g., omalizumab from Cohort A 
with omalizumab from Cohort B) to control for potential confounding of different early 
withdrawal rates by treatment groups. Baseline disease characteristics for each cohort 
(e.g., NCS, NPS, SNOT-22, etc.) will be defined as the last measurement prior to 
randomization in the previous study (GA39688, GA39855).

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6.4
SUMMARIES OF CONDUCT OF STUDY
Descriptive statistics will be used to evaluate the conduct of the study.  The number of 
patients enrolled will be tabulated by study site and by treatment randomized 
(omalizumab or placebo) in the previous study in all patients with data.  Patient 
disposition (the number of patients enrolled, treated, and completing each study period) 
will be tabulated by cohort (and pooled cohorts) by treatment randomized (omalizumab 
or placebo) in the previous study in all patients with data.  Premature study drug 
discontinuation and study discontinuation, as well as reasons for discontinuations, will be 
summarized.  Eligibility criteria deviations and other major protocol deviations will be 
summarized.
6.5
EFFICACY ANALYSES
All efficacy analyses for this study will be presented by cohort and by treatment group 
(four groups: [1] Cohort A omalizumab, [2] Cohort A placebo, [3] Cohort B omalizumab, 
[4] Cohort B placebo).  In addition, if no meaningful differences exist between cohorts
with respect to the comparisons outlined in Section 6.3, and if efficacy results from 
Studies GA39688 and GA39855 appear consistent, the cohorts will be pooled for all
efficacy analyses (two groups: [1] Cohorts A and B omalizumab, [2] Cohorts A and B 
placebo) in addition to being presented separately. 
In all efficacy analyses, baseline will be defined as the last measurement from previous 
studies taken prior to randomization (i.e., baseline of Study GA39688 or GA39855).  This 
definition of baseline is deemed the most meaningful because it allows for comparison of 
treatment regimens (i.e., 52 weeks of omalizumab treatment vs. 24 weeks of placebo 
followed by 28 weeks of omalizumab treatment).  It also allows for a graphical 
assessment of the trajectory of the endpoint over the entire course of a 52-week 
treatment period (over the course of the current and previous studies) in both treatment 
groups.  Assuming that omalizumab is beneficial as compared to placebo, it is expected 
that the distribution of continuous endpoints (e.g., NCS, NPS, etc.) at Week 24 (the 
beginning of this study) will meaningfully differ between the omalizumab and placebo 
groups.  Therefore, it would be inappropriate to define baseline as the measurement 
taken at Week 24. 
6.5.1
Efficacy Analysis Populations
All efficacy analyses will be based on the full analysis set of the OLE study (FAS-OLE), 
consisting of all patients enrolled into this OLE grouped according to the treatment 
assigned (omalizumab or placebo) at randomization of the previous studies.
6.5.2
Primary Efficacy Endpoints
Because the primary analysis is descriptive in nature, there will be no formal hypothesis 
testing in the analysis of the primary efficacy endpoints.

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6.5.2.1
Nasal Polyp Score
Polyp size in each nasal opening will be graded through an assessment of the video 
nasal endoscopy (04 integer scale, see Appendix 3; Gevaert et al. 2013) by a central 
panel of independent sinus surgeons who are blinded to treatment assignment in the 
previous studies.  NPS is the sum of the polyp scores in both nostrils (maximum score 
of 8).  For patients who have had a relatively common surgical procedure called middle 
turbinectomy, scoring will be modified (see Appendix 3).  In addition to all timepoints 
through Week 24 of the previous study, in this OLE study NPS will be assessed on 
Weeks 36, 52, 64, and 76.  Baseline NPS is defined as the last measurement from the 
previous study performed before randomization (i.e., baseline of 
Study GA39688/GA39855).  The absolute change from baseline NPS values will be 
defined as the NPS at the timepoint minus the NPS at baseline.  
Change from baseline of Study GA39688/GA39855 in NPS will be summarized at 
each timepoint by descriptive statistics on observed data (i.e., mean, median, standard 
deviation, and 95% CIs) by treatment group from Study GA39688/GA39855. 
Both efficacy and durability of response will be assessed descriptively and graphically, 
within patients enrolled in the OLE and randomized to omalizumab in 
Study GA39688/GA39855, according to the mean estimates of absolute change from 
baseline in NPS over all timepoints through Week 76, including data from timepoints 
from the previous studies. 
In addition, the durability of response will be assessed, by treatment group from 
Study GA39688/GA39855, by descriptive analysis of the change from baseline at 
Weeks 52, 64, and 76 in NPS.  The duration of response will be assessed in each arm 
separately as the last timepoint at which a meaningful change from baseline in NPS is 
present.
6.5.2.2
Nasal Congestion Score
NCS will be scored by patients as not at all, mild, moderate, or severe (a score of 0, 1, 2, 
or 3, respectively; see Appendix 4; Fairley et al. 1993) every morning through Week 76 
via eDiary.  Details on the calculation of the average daily NCS (i.e., number of days 
included) at baseline and at each timepoint will be provided in the SAP.  In addition to 
monthly timepoints through Week 24 of the previous studies (from patients enrolled in 
the OLE), for each patient and monthly study timepoint of the OLE study (i.e., Weeks 52, 
56, 60, 64, 68, 72, and 76), the NCS for that study visit will be defined as the average of 
the daily scores leading up to that timepoint.  The absolute change from baseline in the 
average daily NCS values will be defined as the average NCS at the timepoint minus the 
average daily NCS at baseline, where baseline is defined as the average of the daily 
NCS over the period leading up to randomization.  Through ongoing monitoring of eDiary 
compliance, investigators will aim to obtain at least 4 of the 7 days of data for NCS in 
any given week.  

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Change from baseline of Study GA39688/GA39855 at each timepoint in NCS will be 
summarized by descriptive statistics on observed data (i.e., mean, median, standard 
deviation, and 95% CIs) by treatment group from Study GA39688/GA39855. Both 
efficacy and durability of response will be assessed descriptively and graphically, within 
patients randomized to omalizumab in Study GA39688/GA39855, according to the mean 
estimates of absolute change from baseline in NCS over all timepoints through Week 76, 
including data from timepoints from the previous studies.
In addition, the durability of response will be assessed, by treatment group from 
Study GA39688/GA39855, by descriptive analysis of the change from baseline at 
Weeks 52, 56, 60, 64, 68, 72, and 76 in NCS.  The duration of response will be 
assessed in each arm separately as the last timepoint at which a meaningful change 
from baseline in NCS is present.
6.5.3
Secondary Efficacy Endpoints
6.5.3.1
Nasal Polyp Score and Nasal Congestion Score
The impact of longer treatment duration on durability of response according to NPS and 
NCS will be assessed separately using two mixed-effect model repeated measurement 
(MMRM) models for NPS and NCS as dependent variables, respectively. The models 
will use absolute change from baseline of Study GA39688/GA39855 as the dependent
variable, adjusted by geographic region through the use of a categorical variable and by 
baseline asthma comorbidity and aspirin sensitivity status, as well as timepoint (at a 
minimum the model will include Weeks 24, 36, 52, 64, and 76), 
Study GA39688/GA39855 baseline NPS (or NCS, respectively), treatment, treatment by 
timepoint interaction, and Study GA39688/GA39855 baseline NPS (or NCS, respectively) 
by timepoint interaction. Further details about the model and additional covariates will 
be described in the SAP.  Point estimates, 95% CIs, and p-values for the treatment 
effect (omalizumab vs. placebo) on absolute change from Study GA39688/GA39855
baseline in NPS (or NCS, respectively) will be calculated on the basis of the model for all 
modeled timepoints, including Week 76, using appropriate contrasts.  
The SAP will describe adjustments, if any, for potential unspecified confounders of 
treatment group differences due to the fact that enrollment into the OLE occurs 
post-randomization into the previous studies.
6.5.3.2
Nasal Symptoms 
Nasal symptoms other than NCS (i.e., TNSS, loss of smell, posterior rhinorrhea, and 
anterior rhinorrhea) will be analyzed according to the same methods as those used for 
NCS score specified in Section 6.5.2.2 and using separate MMRM models as specified 
above.

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6.5.3.3
SNOT-22, UPSIT, EQ-5D-5L, and AQLQ
SNOT-22, UPSIT, EQ-5D-5L, and AQLQ will be analyzed according to the same 
methods as those used for NPS as specified in Section 6.5.2.1 and using separate 
MMRM models as specified above.
6.5.4
Exploratory Efficacy/Psychometric Endpoints
For the for MOS Sleep Scale and Healthy Days Core Module, change from Week 24 to 
Weeks 36, 52, 64, and 76 will be summarized by descriptive statistics on observed data 
(i.e., mean, median, standard deviation, and 95% CIs) by treatment randomized to 
(placebo/omalizumab) from the previous studies. Further details on the analysis of 
reduction in need for surgery, requirement of rescue treatment, having had surgery for 
nasal polyps, MOS Sleep Scale, Healthy Days Core Module, as well as the PGIC will be 
described in the SAP.
6.6
SAFETY ANALYSES
All safety analyses will be based on the subset of the full analysis set of the OLE study
(FAS-OLE) who received at least one dose of omalizumab grouped according to the 
treatment assigned (omalizumab or placebo) at randomization of the previous studies.
Safety will be assessed through the summary of exposure to study drug, adverse events,
and laboratory test results.
Exposure to omalizumab (number of omalizumab administrations and duration of 
treatment) will be summarized for the OLE by treatment group assigned (omalizumab or 
placebo) at randomization of the previous studies.
6.6.1
Primary Safety Analysis: Adverse Events
Verbatim descriptions of treatment-emergent adverse events will be coded and their
incidence will be summarized. A treatment-emergent adverse event is defined as any 
new adverse event reported or any worsening of an existing condition on or after the 
first dose of study drug.  Only adverse events that occurred during the OLE will be 
summarized. In addition, separate summaries will be generated for serious adverse 
events, deaths, adverse events of special interest as defined in Section 5.2.3, and 
adverse events leading to discontinuation of study drug.
6.6.2
Secondary Safety Analysis: Clinical Laboratory Evaluations
Descriptive summaries of laboratory values at Study GA39688/GA39855 baseline and 
throughout the study will be generated for selected parameters. For these selected 
parameters, changes from baseline and the proportion of patients experiencing clinically 
significant changes relative to baseline will be compared between treatment groups as 
randomized in the previous studies.

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6.7
PHARMACOKINETIC/PHARMACODYNAMIC ANALYSES
Predose serum omalizumab concentrations (Cmin) and total and free IgE will be 
measured at Week 36 and Week 52 during the treatment period and at Weeks 64 
and 76 during the follow-up period according to the summary of activities (Appendix 1). 
These concentrations will be summarized using descriptive statistics (mean, standard 
deviation, coefficient of variation, median, minimum, and maximum) by timepoint based 
on the safety analysis population.
Additional PK analyses will be conducted as appropriate.
6.8
INTERIM ANALYSIS
The Sponsor may choose to conduct one interim analysis depending on the results of 
Study GA39688 or GA39855 (e.g., if time to maximum efficacy has not plateaued by 
Week 24).  Results from this interim analysis may be used to support a marketing 
application with health authorities based on results from the previous 
Study GA39688/GA39855. The decision to conduct the optional interim analysis, along 
with the rationale, timing, and statistical details for the analysis, will be documented in 
the SAP prior to the conduct of the interim analysis.  The interim analysis will be 
performed and interpreted by members of the Sponsor study team and appropriate 
senior management personnel, who will be unblinded at the treatment group level.  
Access to treatment assignment information will follow the Sponsor's standard 
procedures. Any optional interim analysis will be performed after database lock of the 
previous studies (Studies GA39688/GA39855).  In this situation, investigators will remain 
blinded to individual treatment assignment from the previous studies 
(Studies GA39688/GA39855).  
6.9
MISSING DATA
Unless otherwise noted, in the analysis of all continuous co-primary, secondary, and 
exploratory endpoints, missing values will not be explicitly imputed in the analyses,
which will be based on descriptive statistics for the co-primary efficacy endpoints and on
mixed-effect model repeated measurement (MMRM) models for the secondary efficacy 
endpoints. Patients without post-baseline efficacy endpoint data will not contribute to the 
MMRM models.
6.10
UNUSED AND SPURIOUS DATA
For the efficacy analysis of continuous co-primary, secondary, and exploratory 
endpoints, a single data point will be assigned to a planned timepoint (e.g., Weeks 4, 8, 
16, 24, 36, 52, 64, and 76) according to the Schedule of Activities for that particular 
endpoint (see Appendix 1) based on the proximity of the date of the assessment to the 
planned timepoint and may include data collected as part of a planned, unscheduled, 
safety follow-up, dosing termination, or early termination visit. All data points collected 
but not assigned to a planned timepoint in the analysis will be unused in the planned 

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analysis. Further details on the assignment of data points to planned timepoints for 
analysis will be described in the SAP.
Due to the nature of the data capture instruments (e.g., eCRF, eDiary, or tablet), 
spurious response data is not expected for PRO efficacy endpoints. In the event of a 
documented device malfunction leading to spurious data (i.e., a date that is recorded 
prior to the date of first patient screened or after last patient's last visit), those data will 
be ignored (assumed missing) for the purpose of efficacy analysis and discussed in the 
Clinical Study Report (CSR). Any spurious lab values or vital sign measurements will be 
excluded from summary tables and discussed in the CSR.
7.
DATA COLLECTION AND MANAGEMENT
7.1
DATA QUALITY ASSURANCE
The Sponsor will be responsible for data management of this study, including quality 
checking of the data.  Data entered manually will be collected via EDC through use of 
eCRFs.  Sites will be responsible for data entry into the EDC system.  In the event of 
discrepant data, the Sponsor will request data clarification from the sites, which the sites 
will resolve electronically in the EDC system.
The Sponsor will produce an EDC Study Specification document that describes the 
quality checking to be performed on the data.  Central laboratory, central imaging, 
eDiary/ePRO, and IWRS data will be sent directly to the Sponsor, using the Sponsor's
standard procedures to handle and process the electronic transfer of these data.
eCRFs and correction documentation will be maintained in the EDC system's audit trail.  
System backups for data stored by the Sponsor and records retention for the study data 
will be consistent with the Sponsor's standard procedures.
Some PRO data will be collected through the use of an electronic device provided by a 
vendor (see Section 7.3 for details).
Some data from patient assessments will be collected on paper and entered into the 
EDC system by site staff.
7.2
ELECTRONIC CASE REPORT FORMS 
eCRFs are to be completed through use of a Sponsor-designated EDC system.  Sites 
will receive training and have access to a manual for appropriate eCRF completion.  
eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor.
All eCRFs should be completed by designated, trained site staff.  eCRFs should be 
reviewed and electronically signed and dated by the investigator or a designee.

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At the end of the study, the investigator will receive patient data for his or her site in a 
readable format on a compact disc that must be kept with the study records.  
Acknowledgement of receipt of the compact disc is required.
7.3
ELECTRONIC PATIENT-REPORTED OUTCOME 
Patients will use an electronic device to capture PRO data.  The device is designed for 
entry of data in a way that is attributable, secure, and accurate, in compliance with 
U.S. FDA regulations for electronic records (21 CFR Part 11).  The data will be 
transmitted to a centralized database maintained by the electronic device vendor.
The electronic data will be available for view access only, via a secure web server.  Only 
identified and trained users may view the data, and their actions will become part of the 
audit trail.  The Sponsor will have view access only.  System backups for data stored by 
the Sponsor and records retention for the study data will be consistent with the 
Sponsor's standard procedures.
Once the study is complete, the data, audit trail, and trial and system documentation will 
be archived.  The investigator will receive patient data for the site in both human- and 
machine-readable formats on an archival-quality compact disc that must be kept with the 
study records as source data.  Acknowledgement of receipt of the compact disc is 
required.  In addition, the Sponsor will receive all data in a machine-readable format on a 
compact disc.
7.4
SOURCE DATA DOCUMENTATION
Study monitors will perform ongoing source data verification and review to confirm that 
critical protocol data (i.e., source data) entered into the eCRFs by authorized site 
personnel are accurate, complete, and verifiable from source documents. 
Source documents (paper or electronic) are those in which patient data are recorded 
and documented for the first time.  They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, PROs, evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies of 
transcriptions that are certified after verification as being accurate and complete, 
microfiche, photographic negatives, microfilm or magnetic media, X-rays, patient files, 
and records kept at pharmacies, laboratories, and medico-technical departments 
involved in a clinical trial.
Before study initiation, the types of source documents that are to be generated will be 
clearly defined in the Trial Monitoring Plan.  This includes any protocol data to be 
entered directly into the eCRFs (i.e., no prior written or electronic record of the data) and 
considered source data.

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Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.6.
To facilitate source data verification and review, the investigators and institutions must 
provide the Sponsor direct access to applicable source documents and reports for 
trial-related monitoring, Sponsor audits, and IRB/EC review.  The study site must also 
allow inspection by applicable health authorities.
7.5
USE OF COMPUTERIZED SYSTEMS
When clinical observations are entered directly into a study site's computerized medical 
record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with health 
authority requirements pertaining to computerized systems used in clinical research.  An 
acceptable computerized data collection system allows preservation of the original entry 
of data.  If original data are modified, the system should maintain a viewable audit trail 
that shows the original data as well as the reason for the change, name of the person 
making the change, and date of the change.
7.6
RETENTION OF RECORDS
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, electronic or paper PRO data (if applicable), Informed Consent 
Forms, laboratory test results, and medication inventory records, must be retained by the 
Principal Investigator for at least 15 years after completion or discontinuation of the 
study or for the length of time required by relevant national or local health authorities, 
whichever is longer.  After that period of time, the documents may be destroyed, subject 
to local regulations.  
No records may be disposed of without the written approval of the Sponsor.  Written 
notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location.
8.
ETHICAL CONSIDERATIONS
8.1
COMPLIANCE WITH LAWS AND REGULATIONS
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the laws and 
regulations of the country in which the research is conducted, whichever affords the 
greater protection to the individual.  The study will comply with the requirements of the 
ICH E2A guideline (Clinical Safety Data Management:  Definitions and Standards for 
Expedited Reporting).  Studies conducted in the United States or under a 
U.S. Investigational New Drug (IND) Application will comply with U.S. FDA regulations 
and applicable local, state, and federal laws.  Studies conducted in the European Union

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or European Economic Area will comply with the E.U. Clinical Trial Directive 
(2001/20/EC).
8.2
INFORMED CONSENT
The Sponsor's sample Informed Consent Form (and ancillary sample Informed Consent 
Forms such as a Child's Informed Assent Form or Mobile Nursing Informed Consent 
Form, if applicable) will be provided to each site.  If applicable, it will be provided in a 
certified translation of the local language.  The Sponsor or its designee must review and 
approve any proposed deviations from the Sponsor's sample Informed Consent Forms 
or any alternate consent forms proposed by the site (collectively, the "Consent Forms") 
before IRB/EC submission.  The final IRB/ECapproved Consent Forms must be 
provided to the Sponsor for health authority submission purposes according to local 
requirements.
If applicable, the Informed Consent Form will contain separate sections for any optional 
procedures.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential risks associated with each optional procedure.  
Patients will be told that they are free to refuse to participate and may withdraw their 
consent at any time for any reason.  A separate, specific signature will be required to 
document a patient's agreement to participate in optional procedures.  Patients who 
decline to participate will not provide a separate signature.
The Consent Forms must be signed and dated by the patient or the patient's legally 
authorized representative before his or her participation in the study.  The case history or 
clinical records for each patient shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study.
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the patient 
to participate.  The final revised IRB/EC-approved Consent Forms must be provided to 
the Sponsor for health authority submission purposes.
Patients must be re-consented to the most current version of the Consent Forms (or to a 
significant new information/findings addendum in accordance with applicable laws and 
IRB/EC policy) during their participation in the study.  For any updated or revised 
Consent Forms, the case history or clinical records for each patient shall document the 
informed consent process and that written informed consent was obtained using the 
updated/revised Consent Forms for continued participation in the study.
A copy of each signed Consent Form must be provided to the patient or the patient's 
legally authorized representative.  All signed and dated Consent Forms must remain in 
each patient's study file or in the site file and must be available for verification by study 
monitors at any time.

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For sites in the United States, each Consent Form may also include patient authorization 
to allow use and disclosure of personal health information in compliance with the U.S. 
Health Insurance Portability and Accountability Act (HIPAA) of 1996.  If the site utilizes a 
separate Authorization Form for patient authorization for use and disclosure of personal 
health information under the HIPAA regulations, the review, approval, and other 
processes outlined above apply except that IRB review and approval may not be 
required per study site policies.
8.3
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE
This protocol, the Informed Consent Forms, any information to be given to the patient, 
and relevant supporting information must be submitted to the IRB/EC by the Principal 
Investigator and reviewed and approved by the IRB/EC before the study is initiated.  
In addition, any patient recruitment materials must be approved by the IRB/EC. 
The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the requirements, 
policies, and procedures established by the IRB/EC.  Investigators are also responsible 
for promptly informing the IRB/EC of any protocol amendments (see Section 9.6).
In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 
local health authority and IRB/EC.  Investigators may receive written IND safety reports 
or other safety-related communications from the Sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health 
authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site's study file. 
8.4
CONFIDENTIALITY
The Sponsor maintains confidentiality standards by coding each patient enrolled in the 
study through assignment of a unique patient identification number.  This means that 
patient names are not included in data sets that are transmitted to any Sponsor location.
Patient medical information obtained by this study is confidential and may be disclosed 
to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law.
Medical information may be given to a patient's personal physician or other appropriate 
medical personnel responsible for the patient's welfare, for treatment purposes.
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 

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be available in accordance with the effective Roche policy on study data publication 
(see Section 9.5).
Data generated by this study must be available for inspection upon request by 
representatives of national and local health authorities, Sponsor monitors, 
representatives, and collaborators, and the IRB/EC for each study site, as appropriate.
8.5
FINANCIAL DISCLOSURE
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study (see definition of end of 
study in Section 3.2).
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION
9.1
STUDY DOCUMENTATION
The investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented, including, but not limited to, the protocol, protocol 
amendments, Informed Consent Forms, and documentation of IRB/EC and 
governmental approval.  In addition, at the end of the study, the investigator will receive 
the patient data, including an audit trail containing a complete record of all changes to 
data.
9.2
PROTOCOL DEVIATIONS
The investigator should document and explain any protocol deviations. The investigator 
should promptly report any deviations that might have an impact on patient safety and 
data integrity to the Sponsor and to the IRB/EC in accordance with established IRB/EC 
policies and procedures.  The Sponsor will review all protocol deviations and assess 
whether any represent a serious breach of Good Clinical Practice guidelines and require 
reporting to health authorities.  As per the Sponsor's standard operating procedures, 
prospective requests to deviate from the protocol, including requests to waive protocol 
eligibility criteria, are not allowed.
9.3
SITE INSPECTIONS
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, patients' medical records, and eCRFs.  The investigator will 
permit national and local health authorities; Sponsor monitors, representatives, and 
collaborators; and the IRBs/ECs to inspect facilities and records relevant to this study.

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9.4
ADMINISTRATIVE STRUCTURE
Omalizumab in the treatment of nasal polyposis is a joint development project between
F. Hoffmann-La Roche Ltd and Novartis Pharmaceuticals. This study is sponsored by
F. Hoffmann-La Roche Ltd and will be managed by F. Hoffmann-La Roche Ltd and a 
contract research organization (CRO). The CRO will manage clinical site operations and 
medical monitoring. 
Approximately 100140 sites globally are expected to participate. It is anticipated that a 
maximum of approximately 240 patients will enroll in this study, as per Section 6.1.  
An IWRS will be used for study drug inventory management and to randomize patients 
to study drug. 
Central facilities will be used for certain study assessments throughout the study 
(e.g., specified laboratory tests and PK and ADA analyses), as specified in Section 4.5.6.  
Accredited local laboratories will be used for routine monitoring; local laboratory ranges 
will be collected.
Samples for urine pregnancy tests will be analyzed at the local laboratory.  Samples for 
PD, PK, and antibody tests will be sent to the Sponsor or a designee for analysis.  
All other samples will be sent to one of several central laboratories for analysis. 
PRO data will be recorded electronically via devices supplied by a PRO vendor.  
Patients will be provided an eDiary device for answering questions on controller 
medication and rescue use.
Endoscopy reads will be read centrally and managed by a central reading vendor.
9.5
PUBLICATION OF DATA AND PROTECTION OF TRADE 
SECRETS
Regardless of the outcome of a trial, the Sponsor is dedicated to openly providing 
information on the trial to healthcare professionals and to the public, both at scientific 
congresses and in peer-reviewed journals. The Sponsor will comply with all 
requirements for publication of study results.  For more information, refer to the Roche 
Global Policy on Sharing of Clinical Trials Data at the following web site:
www.roche.com/roche_global_policy_on_sharing_of_clinical_study_information.pdf
The results of this study may be published or presented at scientific congresses.  For all 
clinical trials in patients involving an IMP for which a marketing authorization application 
has been filed or approved in any country, the Sponsor aims to submit a journal 
manuscript reporting primary clinical trial results within 6 months after the availability of 
the respective Clinical Study Report.  In addition, for all clinical trials in patients involving 
an IMP for which a marketing authorization application has been filed or approved in any 
country, the Sponsor aims to publish results from analyses of additional endpoints and 
exploratory data that are clinically meaningful and statistically sound.

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The investigator must agree to submit all manuscripts or abstracts to the Sponsor prior 
to submission for publication or presentation.  This allows the Sponsor to protect 
proprietary information and to provide comments based on information from other 
studies that may not yet be available to the investigator.
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data.  In this case, a coordinating investigator will be designated by mutual agreement.
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.  Any formal publication 
of the study in which contribution of Sponsor personnel exceeded that of conventional 
monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise.
9.6
PROTOCOL AMENDMENTS
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements.
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information).

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10.
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inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin 
Immunol 2015;136:147685.
Vennera Mdel C, Picado C, Mullol J, et al. Efficacy of omalizumab in the treatment of 
nasal polyps. Thorax 2011;66:8245. doi:10.1136/thx.2010.152835. Epub 25 
November 2010.

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Wang M, Wang X, Zhang N, et al. Association of periostin expression with eosinophilic 
inflammation in nasal polyps. Letter to the Editor. J Allergy Clin Immunol 
2015;136:17003.
We J, Lee WH, Tan KL, et al. Prevalence of nasal polyps and its risk factors: Korean 
National Health and Nutrition Examination Survey 2009-2011. Am J Rhinol 
Allergy 2015;29:e248. doi: 10.2500/ajra.2015.29.4131.
Wenzel SE, Schwartz LB, Langmack EL, et al. Evidence that severe asthma can be 
divided pathologically into two inflammatory subtypes with distinct physiologic and 
clinical characteristics. Am J Respir Crit Care Med 1999;160:10018.
XOLAIR (omalizumab) Summary of product characteristics, Genentech 2003 [cited 
17 October 2016]. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000606/WC500057298.pdf 
Zhang N, Holtappels G, Gevaert P, et al. Mucosal tissue polycolnal IgE is functional in 
response to alergen and SEB. Allergy 
2011;66:1418. doi: 10.1111/j.1398-9995.2010.02448.x.

 
Appendix 1 
Schedule of Activities 
Assessments 
Open-Label Treatment Period 
Follow-Up Period 
Start of 
OLE/Wk24 
Wk 36 
Wk 52 
Wk 56 a 
Wk 60 a 
Wk 64 
Wk 68 a 
Wk 72 a 
Wk 76 
DT/ET b 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
Omalizumab treatment c 
<> 
 
 
 
 
 
 
NPS endoscopy d, e 
x 
x 
 
 
x 
 
 
x 
x 
Nasal symptoms (eDiary) f 
<> 
 
Nasal symptoms 
(interview) g 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SNOT-22 d 
x 
x 
 
 
x 
 
 
x 
x 
EQ-5D-5L d 
 
x 
x 
 
 
x 
 
 
x 
x 
AQLQ d, h 
x 
x 
 
 
x 
 
 
x 
x 
UPSIT d 
 
x 
x 
 
 
x 
 
 
x 
x 
MOS Sleep Scale 
x 
x 
x 
 
 
x 
 
 
x 
x 
Healthy Days Core Module 
x 
x 
x 
 
 
x 
 
 
x 
x 
PGIC 
 
x 
x 
 
 
x 
 
 
x 
x 
PK d, i 
 
x 
x 
 
 
x 
 
 
x 
x 
ADA 
 
 
 
 
 
x 
 
 
x 
x 
Hematology d 
x 
x 
 
 
x 
 
 
x 
x 
Chemistry d 
x 
x 
 
 
x 
 
 
x 
x 
Total IgE i 
 
x 
x 
 
 
x 
 
 
x 
x 
Free IgE i 
 
x 
x 
 
 
x 
 
 
x 
x 
Urine pregnancy test j 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
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Appendix 1
Schedule of Activities (cont.)
Assessments
Open-Label Treatment Period
Follow-Up Period
Start of 
OLE/Wk24
Wk 36
Wk 52
Wk 56 a
Wk 60 a
Wk 64
Wk 68a
Wk 72a
Wk 76
DT/ET b
Weight
x
Limited physical 
examination d
x
x
x
x
x
Vital signsk
x
x
x
x
x
x
Adverse events l
<>
Concomitant medications l,m
<>
ADAanti-drug antibody; AQLQAsthma Quality of Life Questionnaire; DT dosing termination; eDiaryelectronic diary; EQ-5D-5LEuroQol 
5-Dimension 5-Level Questionnaire; ET early termination; MOSMedical Outcomes Study; NPS nasal polyp score; OLEopen-label extension; 
PGICPatient Global Impression of Change; PKpharmacokinetic; PRO patient-reported outcome; Q2W every 2 weeks; Q4W every 4 weeks; 
SNOT-22 Sino-Nasal Outcome Test-22; UPSIT University of Pennsylvania Smell Identification Test; Wk week.
a Telephone visits take place at Weeks 56, 60, 68, and 72 to assess adverse events, concomitant medications, and telephone-based PROs.
b Patients who discontinue study drug or discontinue from the study will be asked to complete the DT/ET visit.
c Patients return to clinic every 2 or 4 weeks to receive open-label omalizumab.  Last omalizumab dose is received at Week 48 for patients 
receiving Q4W dosing and at Week 50 for patients receiving Q2W dosing.
d The following tests/assessments will not be necessary to collect at start of OLE/Week 24 because they are collected at Week 24 of the pivotal 
studies: nasal endoscopy, SNOT-22, EQ-5D-5L, AQLQ, UPSIT, PK, hematology, chemistry, and limited physical examination. A full physical 
examination will not be necessary as part of this OLE study because of the full physical examination at the initiation of Study GA39688 and 
GA39855.
e If initial video endoscopy done during visit is of insufficient quality to allow for assessment of nasal polyps score, patient should return to clinic 
within 10 working days to repeat video endoscopy.   Patients are expected to undergo a total of four endoscopies in this OLE study, except in 
situations in which video endoscopy needs to be repeated because of insufficient quality. 
f
Patients will be instructed to complete the questions in their eDiary in the morning, within approximately 1 hour of awakening. The same 
questions are assessed via eDiary during this OLE study as are being assessed during the treatment period of Study GA39688/GA39855.
g Nasal symptoms with a 7-day recall will be assessed in-clinic via in-person interview at Weeks 24, 36, 52, 64, and 76 and will be assessed via 
telephone interview at Weeks 56, 60, 68, and 72

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Appendix 1
Schedule of Activities (cont.)
h AQLQ only in asthma patients
i
The Week 36 PK, total IgE, and free IgE collection should be conducted prior to the omalizumab dose. 
j
Urine pregnancy testing should be conducted every 4 weeks during the treatment period at Weeks 24, 28, 32, 36, 40, 44, 48, and 52.  Urine 
pregnancy test at Week 24 does not need to be repeated if performed at Week 24 as part of Study GA39688/GA39855 and if completed within 
24 hours of study drug administration as part of the initial visit of this OLE study.
k Vital signs collected at every visit (every 2 weeks in patients receiving omalizumab Q2W and every 4 weeks in patients receiving omalizumab
Q4W).
l
Adverse events and concomitant medications should be assessed and recorded at least monthly.
m Patients will remain on mometasone intranasally throughout the study as specified in Section 4.3.3.  At each visit the investigator must ensure 
that the patient has the necessary doses up to the next visit.

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Appendix 3
Nasal Polyps Scoring System
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 a
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
Notes:  Scoring system is used to evaluate polyp size in each nasal passage by means of 
video nasal endoscopy.  Nasal polyp score is the sum of unilateral polyp scores for each 
nasal passage.  
a The scoring is modified to accommodate patients who have had a middle turbinectomy, 
such that the polyp must reach the top of the inferior turbinate to be graded as Score 2.  
Source:  Gevaert P, Calus L, Van Zele T, et al. Omalizumab is effective in allergic and 
nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol 
2013;131:1106.e1.

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Appendix 5
Nasal Symptoms Assessed via In-Clinic or Telephone Interview
1.
Over the past week, was your nose blocked?
0 Not at all 1 Mild 2 Moderate3 Severe
2.
Over the past week, was your sense of smell reduced?
0 Not at all 1 Mild 2 Moderate3 Severe
3.
Over the past week, did you have a runny nose?
0 Not at all 1 Mild 2 Moderate3 Severe
4.
Over the past week, did you feel dripping at the back of the nose?
0 Not at all 1 Mild 2 Moderate3 Severe
Note:  These nasal symptoms will be assessed in-clinic or via telephone interview, as per 
schedule of activities in Appendix 1.  Study staff will read questions and all responses aloud
verbatim, and patients will respond verbally.  Subject answers will be recorded in the electronic 
data capture system.

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Appendix 8 Asthma Quality of Life Questionnaire

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Appendix 9 EuroQol 5-Dimension 5-Level Questionnaire
Under each heading, please check the ONE box that best describes your health TODAY.
MOBILITY
I have no problems walking.

I have slight problems walking.

I have moderate problems walking.

I have severe problems walking.

I am unable to walk.

SELF-CARE
I have no problems washing or dressing myself.

I have slight problems washing or dressing myself.

I have moderate problems washing or dressing myself.

I have severe problems washing or dressing myself.

I am unable to wash or dress myself.

USUAL ACTIVITIES (e.g., work, study, housework, family or leisure activities)
I have no problems doing my usual activities.

I have slight problems doing my usual activities.

I have moderate problems doing my usual activities.

I have severe problems doing my usual activities.

I am unable to do my usual activities.

PAIN/DISCOMFORT
I have no pain or discomfort.

I have slight pain or discomfort.

I have moderate pain or discomfort.

I have severe pain or discomfort.

I have extreme pain or discomfort.

ANXIETY/DEPRESSION
I am not anxious or depressed.

I am slightly anxious or depressed.

I am moderately anxious or depressed.

I am severely anxious or depressed.

I am extremely anxious or depressed.


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Appendix 10
Medical Outcomes Study Sleep Scale

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Appendix 12
Sampson's Criteria for Diagnosing Potential Cases of 
Anaphylaxis
Anaphylaxis is highly likely when any one of the following three criteria is fulfilled:
1) Acute onset of an illness (minutes to several hours) with involvement of the skin,
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen
lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING:
a)
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced
peak expiratory flow [PEF], hypoxemia)
b)
Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 
(e.g., hypotonia [collapse], syncope, incontinence)
2) Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours):
a)
Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush,
swollen lips-tongue-uvula)
b)
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced
PEF, hypoxemia)
c)
Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope,
incontinence)
d)
Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
3) Reduced BP after exposure to known allergen for that patient (minutes to several 
hours):
a)
Adults:  systolic BP of less than 90 mm Hg or greater than 30% decrease from
that person's baseline
Source:  Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the 
definition and management of anaphylaxis: summary report--Second National Institute of Allergy 
and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin 
Immunol 2006;117:3917.