The ENCORE Study: Safety Evaluation of Repeat Placement of the Corticosteroid-Releasing S8 Sinus Implant in Chronic Sinusitis Patients With Nasal Polyps
Phase: PHASE3
Conditions: Chronic Sinusitis, Nasal Polyposis
Sponsor: Intersect ENT

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL
1 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
CLINICAL STUDY PROTOCOL
1
TITLE PAGE
Study Title
The ENCORE Study: Safety Evaluation of Repeat Placement of the 
Corticosteroid-Releasing S8 Sinus Implant in Chronic Sinusitis 
Patients with Nasal Polyps 
Protocol Number
P500-0717
Doc. Control Number
CP-00015
Investigational Product
S8 Sinus Implant (mometasone furoate, 1350 mcg)
Study Design
Prospective, non-randomized, open-label, multicenter clinical trial
Sponsor’s Name and Address
Intersect ENT, Inc.
1555 Adams Drive
Menlo Park, CA 94025
Tel:  +1 650-641-2100 
Fax: +1 650-641-2053
IND Number
116042
Phase of Development
Phase IIIB
Principal Investigators
R. Peter Manes, MD
Yale School of Medicine
New Haven, CT 06519-1369
Data Management and Study 
Monitoring
Intersect ENT 
Biostatistics and Data 
Analysis
Intersect ENT
This study will be conducted under the guidance of the International Council on Harmonisation (ICH) 
Good Clinical Practice, Clinical investigation of medical devices for human subjects - Good clinical 
practice (BS EN ISO14155: 2011) and other applicable local and federal regulations, including the 
archiving of essential documents.
CONFIDENTIALITY STATEMENT
This document is the property of Intersect ENT. The document is highly confidential and is to be used 
only in connection with matters authorized by a senior representative of Intersect ENT, and no part of it 
is to be disclosed to a third party without prior written permission from Intersect ENT.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL
2 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
TABLE OF CONTENTS
1
TITLE PAGE
...........................................................................................................................................................1
2
LIST OF ABBREVIATIONS
...........................................................................................................................................................4
3
DEFINITIONS OF TERMS
...........................................................................................................................................................5
4
PROTOCOL SUMMARY
...........................................................................................................................................................9
5
STUDY FLOW DIAGRAM
.........................................................................................................................................................14
6
SCHEDULE OF ASSESSMENTS
.........................................................................................................................................................15
7
BACKGROUND INFORMATION
.........................................................................................................................................................16
7.1
Chronic Sinusitis, Treatment Options and Unmet Clinical Need......................................16
7.2
Investigational Product - S8 Sinus Implant .......................................................................17
7.3
Overview of Prior Clinical Studies....................................................................................19
8
STUDY OBJECTIVE
.........................................................................................................................................................20
9
STUDY DESIGN AND ENDPOINTS
.........................................................................................................................................................20
9.1
Study Design......................................................................................................................20
9.2
Study Endpoints.................................................................................................................20
9.3
Other Endpoints .................................................................................................................21
10
SUBJECT SELECTION AND WITHDRAWAL
.........................................................................................................................................................22
10.1
Study Population................................................................................................................22
10.2
Eligibility Criteria..............................................................................................................22
10.3
Subject Withdrawal............................................................................................................24
11
SUBJECT TREATMENT AND STUDY PROCEDURES
.........................................................................................................................................................24
11.1
Screening Phase .................................................................................................................24
11.2
Baseline/Procedure Phase..................................................................................................25
11.3
Follow-Up Phase................................................................................................................27
12
CONCOMITANT MEDICATION
.........................................................................................................................................................28
13
MEDICAL AND SURGICAL INTERVENTIONS
.........................................................................................................................................................29

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL
3 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
13.1
Medical Intervention..........................................................................................................29
13.2
Surgical Intervention..........................................................................................................29
14
ASSESSMENT OF SAFETY
.........................................................................................................................................................30
14.1
Specifications of Safety Parameters...................................................................................30
14.2
Classification of Adverse Events.......................................................................................30
14.3
Guidelines for Reporting of Adverse Events.....................................................................32
15
SAFETY INSTRUCTIONS
.........................................................................................................................................................33
15.1
Contraindications...............................................................................................................33
15.2
Warnings and Precautions..................................................................................................33
15.3
Adverse Reactions .............................................................................................................33
15.4
Patient Counseling .............................................................................................................34
15.5
Potential Benefits from Study Participation ......................................................................34
16
STATISTICAL CONSIDERATIONS
.........................................................................................................................................................35
16.1
Sample Size Calculation ....................................................................................................35
16.2
Analysis of Safety Measures..............................................................................................35
16.3
Analysis of Efficacy Endpoints .........................................................................................35
16.4
Analysis of Other Endpoints..............................................................................................36
16.5
Handling Steroid or Surgical Interventions .......................................................................36
17
STUDY MANAGEMENT
.........................................................................................................................................................36
17.1
Ethical Considerations .......................................................................................................36
17.2
Sponsor Responsibilities....................................................................................................36
17.3
Investigator Responsibilities..............................................................................................38
17.4
Protection of Subject Confidentiality.................................................................................40
17.5
Study Suspension or Early Termination ............................................................................41
17.6
Site Closeout......................................................................................................................42
17.7
Quality Assurance and Supervision by Authorities...........................................................42
17.8
Final Clinical Study Report ...............................................................................................43
17.9
Publication Policy..............................................................................................................43
18
APPENDIX
.........................................................................................................................................................44
Appendix A. List of medications considered as high-dose steroids ...............................................44
19
REFERENCES
.........................................................................................................................................................45

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL
4 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
2
LIST OF ABBREVIATIONS 
Abbreviations
Expansion
AE
adverse event
AS
acute sinusitis
CFR
Code of Federal Regulations
CI
confidence interval
COPD
chronic obstructive pulmonary disease
CRA
clinical research associate
CRF
case report form
CS
chronic sinusitis
CSF
cerebrospinal fluid
CSR
clinical study report
CT
computed tomography
EDC
electronic data capture
e.g.
‘exempli gratia’ in Latin, meaning ‘for example’
ESS
endoscopic sinus surgery
et al
‘et alia’ in Latin, meaning ‘and others’
FDA
Food and Drug Administration
GCP
good clinical practice
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Council on Harmonisation
i.e.
‘id est’ in Latin, meaning ‘that is’
INCS
intranasal corticosteroids
IRB
institutional review board
IUD
intrauterine device
MFNS
mometasone furoate nasal spray
MRI
magnetic resonance imaging
RESS
repeat endoscopic sinus surgery
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SNOT-22
sino-nasal outcome test (22 items)
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment emergent adverse event
UADE
unanticipated adverse device effect

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 5 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
3
DEFINITIONS OF TERMS
Term
Definition
Acute sinusitis (AS)
Per the 2016 “International Consensus Statement on Allergy and 
Rhinology” definition, patient must have inflammation lasting < 4 weeks 
associated with the sudden onset of symptoms such as nasal 
blockage/obstruction/congestion or nasal discharge (anterior/posterior) 
and facial pain/pressure or reduction/loss of smell.
Adverse event (AE)
Any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
[21 CFR 312; BN ES ISO14155]
Adhesion grading scale
Adhesion severity graded on a 5-point scale from 0 to 4 at the 
screening and baseline visits, as follows:
0:
None
1: 
Small but non-obstructing (no separation required)
2:
Obstructing, but easily separated
3: 
Dense and obstructing, separation difficult 
4: 
Severe: complete adhesion of the middle turbinate to the 
lateral nasal wall
Bilateral polyp grade
Sum of left and right polyp grades (see - scale below), resulting in a 
bilateral polyp grade of 0 to 8
Case report form (CRF)
Standardized forms designed to capture monitored data as required by 
the protocol.
Chronic rhinosinusitis with nasal 
polyps 
Per the 2016 “International Consensus Statement on Allergy and 
Rhinology” definition, patient must have ≥ 12 weeks of:

Two or more of the following symptoms:
o
Mucopurulent discharge (rhinorrhea or postnasal drip)
o
Nasal obstruction and congestion
o
Decreased/absent sense of smell
o
Facial pressure/pain

And one or more of the following findings:
o
Evidence of inflammation on paranasal sinus 
examination or computed tomography
o
Evidence of purulence coming from paranasal sinuses 
or ostiomeatal complex

And presence of polyps. 
Enrolled
Subjects are considered enrolled upon signing the informed consent 
form. 
High-dose steroids
The following steroids are considered as high-dose in the study: oral, 
parenteral, injections, budesonide or other sinus steroid irrigations, 
rinses or drops, nebulized steroids administered nasally.
Implant delivery success
Successful deployment of the S8 Sinus Implant to the target site. 
Deployment is considered successful if the procedure concludes with a 
successful placement in the target sinus, even if a second attempt is 
required. Implant delivery success rate is calculated as proportion of 
successful deployments of the S8 Sinus Implant to the target site per 
total number of sinuses attempted including the baseline and repeat 
placement procedures. 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 6 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Term
Definition
Malfunction
Failure of an investigational medical device to perform in accordance 
with its intended purpose when used in accordance with the instruction 
for use or clinical investigation plan. [BS EN ISO14155] 
Failure of a device to meet its performance specifications or otherwise 
perform as intended. Performance specifications include all claims made 
in the labeling for the device. The intended performance of a device 
refers to the intended use for which the device is labeled or marketed. 
[21CFR 803]
Nasal obstruction/congestion scale
A 4-point scale defined as follows: 
0:
No symptoms
1:
Mild symptoms, clearly present but minimal awareness and 
easily tolerated
2:
Moderate symptoms, definite awareness of symptoms that is 
bothersome but tolerable
3:
Severe symptoms, hard to tolerate, cause interference with 
activities or daily living
Percent ethmoid sinus obstruction
Estimated visually based on endoscopic examination on a scale ranging 
from 0% (no obstruction) to 100% (complete obstruction of the ethmoid 
cavity by polyps, edema and/or scarring). 
Polyp grading scale
Polyps are assessed endoscopically and graded on an 8-point scale 
ranging from 0 to 4 defined as follows: 
0:
No visible sinonasal polyps
1:
Small amount of sinonasal polyps confined in middle meatus
1.5: Small amount of sinonasal polyps confined in middle meatus 
with expanded amount of polypoid edema obstructing ≥ 25% 
of the ethmoid sinus cavity
2:
Expanded amount of sinonasal polyps confined in middle 
meatus
2.5: Expanded amount of sinonasal polyps confined in middle 
meatus with expanded amount of polypoid edema obstructing 
≥ 50% of the ethmoid sinus cavity
3:
Sinonasal polyps extending beyond middle meatus but not 
totally obstructing the nasal cavity
3.5: Sinonasal polyps extending beyond middle meatus with 
expanded amount of polypoid edema obstructing ≥ 75% of 
the ethmoid sinus cavity
4:
Sinonasal polyps extending beyond middle meatus and 
completely obstructing the nasal cavity
Serious adverse event (SAE) or 
serious suspected adverse reaction 
(SSAR)
Adverse events are considered “serious” if, in the view of either the 
investigator or sponsor, they result in any the following outcomes:

Death; or

A life-threatening adverse event; or

Inpatient hospitalization or prolongation of existing 
hospitalization; or

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 7 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Term
Definition

A persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions; 
or 

A congenital anomaly/birth defect.
Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, 
based upon appropriate medical judgment, they may jeopardize the 
patient and may require medical or surgical intervention to prevent one 
of the outcomes listed in this definition. [21 CFR 312]
Suspected unexpected serious 
adverse reaction (SUSAR)
Any SSAR that is unexpected. [21 CFR 312]
Suspected adverse reaction (SAR) 
Any AE for which there is a reasonable possibility that the drug caused 
the AE. Reasonable possibility means there is evidence to suggest a 
causal relationship between the drug and the adverse event. Suspected 
adverse reaction (SAR) implies a lesser degree of certainty about 
causality than adverse reaction, which means any adverse event caused 
by a drug. [21 CFR 312]
Sino-Nasal Outcome Test (SNOT-
22)
A validated, disease-specific, symptom-scoring instrument consisting of 
22 questions, each scored on a scale of 0 to 5 defined as follows:
0: 
No problem
1: 
Very mild problem
2: 
Mild or slight problem
3: 
Moderate problem
4: 
Severe problem
5:
Problem as bad as it can be
Source data
All information in original records and certified copies of original 
records of clinical findings, observations, or other activities in a clinical 
trial necessary for the reconstruction and evaluation of the trial. 
Source documents
Original documents, data, and records. Printed, optical or electronic 
document containing source data. 
Subject
An individual who participates in a clinical investigation. 
Treatment emergent adverse event 
(TEAE)
Any event not present prior to the treatment or an event already present 
that worsens either in intensity or frequency following the treatment.
Unanticipated Adverse Device 
Effect (UADE)
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application, or any 
other unanticipated serious problem associated with a device that relates 
to the rights, safety, or welfare of subjects. [BS EN ISO 14155]
Unanticipated Serious Adverse 
Device Effect (USADE)
Any serious adverse device effect which by its nature, incidence, severity 
or outcome has not been identified in the current version of the risk 
analysis report. [21 CFR 812]
Unexpected adverse event or 
suspected adverse reaction
An AE/SAR is considered ‘unexpected’ if it is not listed in the 
investigator brochure or is not listed at the specificity or severity that has 
been observed. Unexpected events also refer to AE/SARs that are 
mentioned in the investigator brochure as occurring with a class of 
product or as anticipated from the pharmacological properties of the 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 8 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Term
Definition
product, but are not specifically mentioned as occurring with the 
particular investigational product. [21 CFR 312]

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 9 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
4
PROTOCOL SUMMARY
Study Title
The ENCORE Study: Safety Evaluation of Repeat Placement of the 
Corticosteroid-Releasing S8 Sinus Implant in Chronic Sinusitis Patients 
with Nasal Polyps
Objective
To assess the safety of repeat placement of the S8 Sinus Implant when 
used in chronic sinusitis (CS) patients with recurrent nasal polyps
Investigational Product
The S8 Sinus Implant (mometasone furoate, 1350 mcg) is a 
bioabsorbable, corticosteroid-eluting implant studied for the treatment of 
nasal polyps in patients ≥ 18 years of age who have had ethmoid sinus 
surgery.
The S8 Sinus Implant is placed in the ethmoid sinus under endoscopic 
visualization. The implant may be left in the sinus to gradually release the 
corticosteroid over approximately 90 days. The implant must be removed 
by 90 days after placement or may be removed earlier at the 
investigator’s discretion, using standard surgical instruments. 
Study Design
A prospective, non-randomized, open-label, multicenter clinical trial, 
consisting of three phases: 
Screening

Patients who sign the institutional-review board (IRB) approved 
informed consent form will be considered enrolled into the study.

All consented subjects will undergo a screening assessment 
consisting of an endoscopic examination. 
Baseline/Procedure

Eligible subjects will undergo a baseline assessment. 

Subject meeting all eligibility criteria will undergo an in-office 
bilateral placement of the S8 Sinus Implant in the ethmoid 
sinuses.
Follow-up

Subjects will return for 7 follow-up visits at Days 30, 60, 90, 120, 
150, 180 and 365.

At the Day 90 visit, subjects will undergo repeat in-office 
placement of the S8 Sinus Implant in each ethmoid sinus with 
nasal polyps (grade ≥ 1). Repeat placement will not be performed 
if polyp grade is < 1, or if the subject declines the procedure.
Subject Enrollment
A total of 50 subjects will be treated at up to 10 study centers across the 
U.S. with a maximum of 15 treated subjects at a single center.
Study Population
Patients ≥ 18 years of age with CS who have undergone prior endoscopic 
sinus surgery (ESS), including bilateral total ethmoidectomy, and present 
with bilateral ethmoid polyposis, and in whom bilateral placement of the 
S8 Sinus Implant is both feasible and medically appropriate. 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 10 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Eligibility Criteria
Key inclusion criteria:

Confirmed diagnosis of CS with nasal polyps. Per the 2016, 
“International Consensus Statement on Allergy and Rhinology” 
definition, patient must have ≥ 12 weeks of:
o
Two or more of the following symptoms:

Mucopurulent discharge (rhinorrhea or postnasal 
drip)

Nasal obstruction and congestion

Decreased/absent sense of smell

Facial pressure/pain
o
And one or more of the following findings:

Evidence of inflammation on paranasal sinus 
examination or computed tomography

Evidence of purulence coming from paranasal 
sinuses or ostiomeatal complex 
o
And presence of polyps.

Previous ESS including bilateral total ethmoidectomy at least 90 
days prior to screening.

Patient must have evidence of bilateral ethmoid sinus polyps 
(grade ≥ 2 on each side)

Ethmoid sinus anatomy is amenable to bilateral placement of the 
S8 Sinus Implant (20 mm nominal length, 7 mm compressed 
diameter)
Key exclusion criteria:

Extensive ethmoid sinus polyps (grade 4 on at least one side) 

Extensive adhesions/synechiae (grade 3 or 4)

Oral-steroid dependent condition

History of allergy or intolerance to corticosteroids or mometasone 
furoate

Physical obstruction that would preclude access to or placement 
of the S8 Sinus Implant in the middle meatus

Evidence of acute sinusitis (AS), invasive fungal sinusitis or 
another disease or condition expected to compromise survival or 
ability to complete assessments during the 180-day follow-up 
period

Use of parenteral and injected steroids (e.g., Kenalog injection) 
30 days prior to the baseline procedure 

Use of monoclonal antibodies (e.g., Dupoxent, Nucala, Xolair) 
for treatment for asthma, allergies or nasal polyps 30 days prior to 
the baseline procedure

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 11 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.

Use of oral steroids, budesonide or other sinus steroid 
irrigations/rinses, nebulized steroids administered nasally or 
budesonide drops 14 days prior to the baseline procedure
Safety Evaluation 
All adverse events reported by subjects between consent and the Day 365 
follow-up visit (end of study) will be tabulated. 
Each adverse event will be evaluated by investigators in terms of 
seriousness, severity (i.e., mild, moderate, severe) and strength of 
relationship (i.e., not related, unlikely related, possibly related, related) to 
study drug, study device, and implant procedure. 
Efficacy Endpoints
Patient-reported endpoints: 

Change from baseline to each time-point (Days 30, 60, 90, 120, 
150, 180) in the mean nasal obstruction/congestion score (scale 
0 to 3) based on a reflective questionnaire

Change from baseline to each time-point (Days 30, 60, 90, 120, 
150, 180) in SNOT-22 total score (scale 0 to 110), domain scores 
and individual symptom scores (scale 0 to 5) 
Endoscopic endpoints: 

Change from baseline to each time-point (Days 30, 60, 90, 120, 
150, 180) in bilateral polyp grade (scale 0 to 8) 

Change from baseline to each time-point (Days 30, 60, 90, 120, 
150, 180) in ethmoid sinus obstruction (scale 0% to 100%) 
Other Endpoints
Implant delivery success rate: 

Proportion of successful deployments of the S8 Sinus Implant to 
the target site including the baseline and repeat placement 
procedures. See Section 3 Definition of terms
Interventions received:

Proportion of subjects who received interventions (i.e., sinus-
related medications, systemic steroid interventions, surgical 
interventions for sinusitis) through Day 365 
Concomitant 
Medications

After the baseline procedure, subjects will be encouraged to use 
saline rinses regularly through Day 365.

After the baseline procedure, subjects will be required to use 
MFNS 200 mcg (two sprays in each nostril) once daily 
throughout the whole duration of the follow-up, unless the use of 
MFNS is not warranted clinically. Both the generic version of 
MFNS by Apotex or Novartis and the brand-name version by 
Merck (Nasonex) can be used. 

High-dose steroids (e.g., oral, parenteral, injections, budesonide 
or other sinus steroid irrigations/rinses or drops, nebulized 
steroids administered nasally) will be allowed during the study 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 12 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
follow-up only if clinically necessary. (see Medical and Surgical 
Interventions)

Orally-inhaled steroids for control of asthma will be permitted.

If infection is suspected at any time during the study, treatment 
with antibiotics will be permitted.

Use of monoclonal antibodies is prohibited throughout the 365-
day follow-up period.

To the extent possible, subjects will be maintained on stable 
regimens of leukotriene inhibitors and/or immunotherapy for 
allergies, if currently on such regimens; however, use of breath-
powered or other methods of intranasal steroid delivery for 
allergies is not permitted during the study.

Use of drug-eluting implants (PROPEL®, PROPEL® Mini, 
PROPEL® Contour) is prohibited during the baseline procedure 
and throughout the 365-day follow-up unless placed immediately 
following repeat ESS performed in the operating room setting.
Medical and Surgical 
Interventions
Medical interventions: 

During the study follow-up, high-dose steroids (e.g., oral, 
parenteral, injection, budesonide or other sinus steroid irrigations, 
rinses or drops, nebulized steroids administered nasally) may be 
used as a medical intervention in cases where a clinically 
significant increase or persistence in ethmoid sinus polyposis 
occurs, leading to subject seeking intervention. 

High-dose steroids may be used for reasons other than ethmoid 
sinus obstruction, if medically necessary. 

In either case, high-dose steroid interventions and reasons of their 
use will be recorded on the concomitant medication and follow-
up case report forms (CRF).
Surgical interventions:

During the study follow-up, surgical intervention (e.g., repeat 
ESS, office polypectomy) may be required in cases where a 
clinically significant increase or persistence in ethmoid sinus 
polyposis occurs. 
Follow-up
Each subject will return for 7 follow-up visits:

Day 30 (± 7 days)

Day 60 (± 7 days)

Day 90 (± 7 days) implant removal & repeat placement

Day 120 (± 7 days)

Day 150 (± 7 days) 

Day 180 (± 14 days) implant removal

Day 365 (± 14 days) 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 13 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Subjects may come in for additional unscheduled office visits if 
necessary. Circumstances that may warrant additional visits include, but 
are not limited to worsening of sinus symptoms, sinus-related adverse 
events requiring medical evaluation, and implant migration. 
Study Duration
The anticipated timeline for this study is as follows:

Enrollment start: November 2017

Enrollment end: January 2018

Follow-up end: November 2018
Duration of Study Period 
(per subject)
Screening visit (1 day) + baseline/procedure (1 day) + follow-up (365 
days) = Approximately 367 days

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 14 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
5
STUDY FLOW DIAGRAM
Enrollment/Screening
Medications
Study Population
Adult (≥ 18 years ) patients with 
chronic sinusitis and nasal polyps
(grade 2-3.5 on each side)
Prior bilateral total ethmoidectomy
Abbreviations: 
SNOT-22, Sino-Nasal Outcome Test 
Prior to the baseline procedure:
No parenteral steroids or 
monoclonal antibodies for ≥30 
days
No oral steroids, budesonide or 
other steroid irrigations or rinses, 
nebulized nasally steroids, or 
budesonide drops for ≥ 14 days
Mometasone Furoate Nasal 
Spray 2 sprays in each nostril once 
daily after baseline procedure 
through Day 365, unless not 
warranted clinically
Saline rinses to be used regularly
High-dose steroids (e.g oral, 
parenteral, injection, budesonide 
respules, rinses or drops, steroid 
nebulizers administered nasally) 
allowed only if clinically necessary
Repeat ESS allowed if clinically 
necessary
Antibiotics allowed if clinically 
necessary 
Day 30 (± 7 days)
Endoscopic grading
ENT
Subject
Endoscopic grading
(before implant placement)
Endoscopic grading
SNOT-22, Nasal Obstr/Cong 
(before implant placement)
SNOT-22, Nasal Obstr/Cong
Sample Size
N=50
Topical Anesthesia
Bilateral Placement
Day 60 (± 7 days)
Endoscopic grading
SNOT-22, Nasal Obstr/Cong
Day 90 (± 7 days)
Endoscopic grading
Implant removal
Repeat placement
SNOT-22, Nasal Obstr/Cong
Day 120 (± 7 days)
Endoscopic grading
SNOT-22, Nasal Obstr/Cong
Day 150 (± 7 days)
Endoscopic grading
SNOT-22, Nasal Obstr/Cong
Day 180 (± 14 days)
Endoscopic grading
Implant removal
SNOT-22, Nasal Obstr/Cong
Day 365 (± 14 days)

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 15 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
6
SCHEDULE OF ASSESSMENTS
Assessment
Screening
Baseline/Procedure
Day 30 (± 7 days)
Day 60 (± 7 days)
Day 90 (± 7 days)
Day 120 (± 7 days)
Day 150 (± 7 days)
Day 180 (± 14 days)
Day 365 (± 14 days)
Informed consent
X
Medical/surgical history
X
Endoscopic grading & recording
X
X
X
X
X
X
X
X
Nasal Obstruction/Congestion
X
X
X
X
X
X
X
Sino-Nasal Outcome Test (SNOT-22) 
X
X
X
X
X
X
X
In-office implant placement (bilateral)
X
Implant removal
X
X
In-office repeat placement (unilateral or bilateral)
Xa
Concomitant medications 
X
X
X
X
X
X
X
X
X
Adverse events reporting
X
X
X
X
X
X
X
X
X
Pregnancy test (female subjects)
Xb
Xb
Xb
Documented birth control (female subjects)
Xc
X
X
X
X
X
X
X
Note: If screening and baseline/procedure visits occur on the same day, assessments must be recorded on the 
baseline visit forms.
a. Repeat implant placement will be performed at Day 90 in each ethmoid sinus with polyp grade ≥ 1 (See 
Section 11.3 Repeat Implant Placement Procedure). 
b. Female subjects with reproductive potential are required to undergo a urine pregnancy test at screening and 
prior to the baseline procedure. If the screening and baseline/procedure visits occur on the same day, only one 
urine pregnancy test is required prior to the baseline procedure.  The pregnancy test must be repeated at Day 
90 prior to repeat implant placement procedure.
c. Female subjects are required to confirm their nursing status at baseline.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 16 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
7
BACKGROUND INFORMATION
7.1
Chronic Sinusitis, Treatment Options and Unmet Clinical Need
Chronic sinusitis (CS) is a prevalent disease process affecting 32 million Americans, 
corresponding to 13% of the adult population (Blackwell 2014). CS results in 18 to 22 million 
U.S. physician office visits annually, representing considerable health care expenditures 
(Bhattacharyya 2011, Caulley 2015). Patients with CS with nasal polyps have a higher burden 
of symptoms, revision sinus surgery, and greater use of medications. The presence of polyps 
negatively affects the ability of the otolaryngologists to treat patients and patients are subject to 
frequent relapses. 
The myriad of clinical management options demonstrates the lack of long-term effectiveness of 
any single treatment option for CS with nasal polyps (Joe 2008). This is best explained by the 
multi-factorial pathophysiology of CS with nasal polyps (Han 2013). Medical management with 
topical and possibly systemic corticosteroids are considered the initial treatment strategy of 
choice, with endoscopic sinus surgery (ESS) reserved for patients whose CS with nasal polyps 
fail to improve. Surgical treatment with polypectomy temporarily relieves ostiomeatal complex 
blockage and improves ventilation but is not curative (Fokkens 2012, Manes 2013). Nasal 
polyps have a strong tendency to recur in up to 40% of patients within 1.5 years after surgery 
(DeConde 2016) and 60% within 3 years (Wynn 2004) even when aeration is improved. 
Furthermore, about 20% of patients undergo revision surgery within 5 years after initial surgery 
(Philpott 2015, Wu 2014). 
Systemic corticosteroids have been shown to enhance the efficacy of surgical approaches but 
result in numerous adverse events such as gastrointestinal symptoms, adrenal suppression, 
insomnia, increased bone turnover, and epistaxis (Orlandi 2016, Poetker 2013). The 
development of corticosteroids that are delivered directly to the nasal mucosa has addressed 
much of the concern about the systemic adverse effects associated with systemic corticosteroid 
therapy (Fandino 2013, Sastre 2012, Wei 2013). However, intranasal topical preparations often 
fail because of limited penetration to the target sinus anatomy due to blockage of ostiomeatal 
complex by polyposis, crusting, secretions, and/or edema which limit delivery of an adequate 
amount of drug to the sinuses. Moreover, patient compliance with daily dosing of topical 
preparations and proper head position may compromise drug delivery and reduce efficacy 
(Sanan 2017). 
Current therapies for CS with nasal polyps have been tailored to improving postoperative 
aeration and minimizing sinonasal inflammation in hopes of decreasing polypoid regrowth 
(Santarelli 2016). Intersect ENT has developed the S8 Sinus Implant to provide an in-office 
option, independent of patient compliance, for treating recurrent CS with nasal polyps after 
ESS. 
The efficacy and safety of a single-use bilateral placement of the S8 Sinus Implant was studied 
as part of the S8 clinical program. This Phase IIIb study is designed to assess the safety of 
repeat placement of the S8 Sinus Implant when used in chronic sinusitis (CS) patients with 
recurrent nasal polyps.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 17 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
7.2
Investigational Product - S8 Sinus Implant 
Intended use
The S8 Sinus Implant is indicated for the treatment of nasal polyps in patients ≥ 18 years of age 
who have had ethmoid sinus surgery. 
Description
The S8 Sinus Implant is designed to accommodate the size and variability of a previously 
operated ethmoid sinus cavity. Once inserted under endoscopic visualization, the S8 Sinus 
Implant is designed to be self-retaining within the cavity. The S8 Sinus Implant is intended to 
provide an immediate onset of action by mechanical dilation of the middle meatus and ethmoid 
sinus with concurrent restoration of ventilation and drainage by decreasing nasal 
obstruction/congestion, inflammation and polyposis through local steroid delivery. Therefore, 
the S8 Sinus Implant combines a device mode of action (mechanical opening) with a drug mode 
of action (reduced inflammation).
Figures 1a-b depict the structure of the S8 Sinus Implant. The structural design features are the 
rounded cap at the leading end and the arched components that expand after placement to create 
an opening within ethmoid cavity. The arched components run through the cap to provide the 
shape of the implant. The resulting self-expanding nature of the implant provides an outward 
force against the mucosal surfaces. The alternating lengths of the implant legs are 25 and 20 
mm. This feature assists with retention of the implant within the sinus. When expanded to the 
dimensions of a typical operated ethmoid sinus cavity, the S8 Sinus Implant is approximately 20 
mm in nominal length and can expand to a nominal diameter of 34 mm. Figure 2a shows an 
ethmoid cavity obstructed by scarring and polyps; Figure 2b shows the S8 Sinus Implant 
immediately after placement, dilating the obstructed by polyps ethmoid sinus seen in Figure 2a 
to create an opening that permits ventilation and drainage to occur. 
Figure 1a. S8 Sinus Implant in an 
expanded state
Figure 1b. S8 Sinus Implant in a crimped 
state loaded onto the delivery system
25mm
20mm
Cap

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 18 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Figure 2a. Endoscopic view of the 
ethmoid cavity obstructed by scarring 
and polyposis before placement of the 
S8 Sinus Implant
Figure 2b. Endoscopic view of the ethmoid 
cavity depicted in 2a after placement of the S8 
Sinus Implant. Note dilation effect and 
creation of opening 
Composition
The S8 Sinus Implant is composed of a blend of two different ratios of a synthetic 
bioabsorbable co-polymer, poly(L-lactide-co-glycolide) with different lactide/glycolide ratios. 
The implant has a coating containing mometasone furoate (active ingredient), a synthetic 
corticosteroid with anti-inflammatory activity. The chemical name is 9α, 21-dichloro-11β,17α -
dihydroxy-16α -methylpregna-1,4-diene-3,20-dione 17-(2-furoate), with the empirical formula 
C27H30Cl2O6, and a molecular weight of 521.43 g/mol. The drug is embedded in a bioabsorbable 
polymer matrix containing poly-(DL-lactide-co-glycolide) and polyethylene glycol (inactive 
ingredients) which provides for gradual release of the drug. This top coating is designed to 
provide a controlled release of mometasone furoate over the course of 90 days. 
Crimper and delivery system 
The implant comes pre-assembled in a crimper. The crimper holds the implant during shipping 
and works in concert with the delivery system to crimp and load the implant. The delivery 
system is designed to be single-handed, allowing the physician to place the implant under 
endoscopic guidance. 
The delivery system is designed to provide access to the ethmoid sinus and controlled accurate 
deployment of the implant. The delivery system comprises the thumb and finger rests, the 
seeker and a cup (Figure 3). The seeker is extended by pushing with the thumb rest to load the 
implant onto the delivery system. The tip of the delivery system has a curvature of 10° to 
facilitate endoscopic placement.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 19 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Figure 3. Delivery system
General instructions for placement
The S8 Sinus Implant must be placed according to the prescribing information. To summarize, 
the S8 Sinus Implant is crimped and loaded by introducing the delivery system’s seeker tip into 
the center of the implant, depressing the finger rests to extend the seeker and allowing the cup to 
capture all legs of the implant. For endoscopic placement, the thumb rest is pressed again to 
release the implant from the distal tip of the seeker into the ethmoid cavity. Upon release, the S8 
Sinus Implant expands radially to conform to and dilate the sinus tissue. The delivery system is 
then retracted out of the patient. Final placement is confirmed by endoscopic visualization. The 
position of the S8 Sinus Implant can be adjusted after placement using the seeker on the 
delivery system.
7.3
Overview of Prior Clinical Studies 
The safety and efficacy of the S8 Sinus Implant have been evaluated in four US clinical studies: 
two controlled and two uncontrolled, totaling 417 CS with nasal polyps patients. 
Controlled studies
The two randomized, sham-controlled, parallel group, single-blind, multicenter studies were 
P500-1113 RESOLVE II (N = 300) and P500-1012 RESOLVE (N = 100). The RESOLVE II 
study was a Phase III clinical trial designed to demonstrate the efficacy and safety of the S8 
Sinus Implant by evaluating the patient-reported symptoms of nasal obstruction and congestion 
and the objective endoscopic measure of bilateral polyp grade as co-primary efficacy endpoints. 
RESOLVE II also included a prespecified plan to test five secondary efficacy endpoints, which 
are clinically relevant for this patient population. 
Uncontrolled studies
The two uncontrolled studies were P500-0911 S8 Pilot (N = 12) and P500-0513 S8 PK (N = 5). 
The S8 Pilot assessed and demonstrated the feasibility and safety of implant placement and its 
initial signals of efficacy (Lavigne 2014). The S8 PK study assessed implant delivery to the 
ethmoid sinus and systemic exposure to mometasone furoate by measuring plasma mometasone 
furoate concentrations through 30 days post-procedure (Ow 2014). 
Thumb Rest
Finger Rests
Seeker
Cup
Shaft
Shaft Length

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 20 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Overall efficacy and safety conclusions
The efficacy results from RESOLVE II and RESOLVE in 400 subjects demonstrated that 
bilateral placement of the S8 Sinus Implant provides compelling benefits consisting of early 
onset of symptomatic relief and endoscopic improvements in CS with nasal polyps patients who 
had undergone previous ESS but still presented with symptoms refractory to medical therapy 
and were candidates for RESS. Treatment effects were maintained long term (6 months). 
The safety results from the four clinical studies with 417 subjects supported favorable safety 
profile, including high patient acceptance, negligible systemic exposure, negligible ocular risk, 
and overall low implant-related adverse events, making it an appealing, minimally invasive 
topical therapy strategy for patients with CS with nasal polyps.
8
STUDY OBJECTIVE
To assess the safety of repeat placement of the S8 Sinus Implant when used in CS patients with 
recurrent nasal polyps. 
9
STUDY DESIGN AND ENDPOINTS
9.1
Study Design
This is a prospective, non-randomized, open-label, multicenter clinical trial. A total of 50 
subjects will be treated at up to 10 study centers across the U.S. with a maximum of 15 subjects 
treated at a single center. 
The study will consist of three phases: screening, baseline/procedure and follow-up. The total 
duration of an individual subject’s study participation will be approximately 367 days.
9.2
Study Endpoints
9.2.1
Safety Evaluation
All AE reported by subjects between consent and the Day 365 follow-up visit (end of study) 
will be tabulated. 
Each AE will be evaluated by investigators in terms of seriousness, severity (i.e., mild, 
moderate, severe) and strength of relationship (i.e., not related, unlikely related, possibly 
related, related) to study drug, study device, and implant procedure.
9.2.2
Efficacy Endpoints
Efficacy endpoints will consist of both patient-reported and endoscopic outcomes through Day 
180 follow-up visit.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 21 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Patient-reported endpoints

Change from baseline to each time-point (Days 30, 60, 90, 120, 150, 180) in the mean 
nasal obstruction/congestion score (scale 0 to 3)

Change from baseline to each time-point (Days 30, 60, 90, 120, 150, 180) in SNOT-22 
total score (scale 0 to 110), domain scores and individual symptom scores (scale 0 to 5)
Subjects will assess their CS sinus symptoms during each visit using paper questionnaires.
 See Section 3 Definitions of Terms and Section 6 Schedule of Assessments for details on 
scoring scales and timing of assessments.
Endoscopic endpoints

Change from baseline to each time-point (Days 30, 60, 90, 120, 150, 180) in bilateral 
polyp grade (scale 0 to 8) 

Change from baseline to each time-point (Days 30, 60, 90, 120, 150, 180) in ethmoid 
sinus obstruction (scale 0% to 100%)
Investigators will perform endoscopic evaluation with real-time grading and video recording. 
When grading polyps for this study, investigators will be instructed to consider only polyps 
originating from the ethmoid sinus/middle meatus and focus within the anatomical boundaries 
of the ethmoid sinus. Grading should not include polyps medial to the middle turbinate, polyps 
originating from the maxillary sinus, or polyps within the sphenoethmoid recess. Investigators 
will also be instructed to consider and account for polypoid edema if present in an expanded 
amount in the ethmoid sinus and middle meatus.
See Section 3 Definitions of Terms and Section 6 Schedule of Assessments for details on 
endoscopic grading scales and timing of assessments.
9.3
Other Endpoints
Implant delivery success rate
Proportion of successful deployments of the S8 Sinus Implant to the target site per total number 
of sinuses attempted including the baseline and repeat placement procedures. 
Interventions received
Proportion of subjects who received interventions (i.e., sinus-related medications, systemic 
steroid interventions, surgical interventions) through Day 365.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 22 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
10
SUBJECT SELECTION AND WITHDRAWAL
10.1 Study Population
The study population will consist of adult patients (≥ 18 years of age) with CS who have 
undergone prior ESS including bilateral total ethmoidectomy and present with bilateral ethmoid 
polyposis, and in whom bilateral placement of the S8 Sinus Implant is both feasible and 
medically appropriate. 
10.2 Eligibility Criteria
To be enrolled in the study, patients must meet all of the following inclusion criteria and none of 
the following exclusion criteria.
Inclusion criteria
a.
Patient has provided written informed consent using a form approved by the 
reviewing institutional review board (IRB) and sponsor.
b. Patient is ≥ 18 years of age.
c.
Patient is willing and able to comply with protocol requirements.
d. Patient has a confirmed diagnosis of CS with nasal polyps, as defined in the 2016 
“International Consensus Statement on Allergy and Rhinology”.
e.
Patient has undergone prior ESS including bilateral total ethmoidectomy at least 90 
days prior to screening.
f.
Patient has evidence of bilateral ethmoid sinus obstruction due to polyposis 
warranting intervention (polyp grade ≥ 2 on each side).
g. Patient is able to tolerate daily use of Mometasone Furoate Nasal Spray (MFNS).
h. Patient is able to tolerate topical/local anesthesia.
i.
In the opinion of the investigator, patient’s ethmoid sinus anatomy is amenable to 
in-office bilateral placement of the S8 Sinus Implant (i.e., able to pass into the 
middle meatus on both sides the S8 Sinus Implant with 20 mm in nominal length 
and 7 mm in compressed diameter).
j.
Female patients of reproductive potential must not be pregnant or nursing and must 
agree to not become pregnant during their participation in the study.
k. Female patients of childbearing potential must agree to use consistent and 
acceptable method(s) of birth control during their participation in the study.
Exclusion criteria
a.
Patient has extensive ethmoid sinus polyp grade (grade 4 on at least one side).
b. Patient has extensive adhesions/synechiae (grade 3 or 4). 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 23 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
c.
Patient has used parenteral and injected steroids (e.g., Kenalog injection) during 30 
days prior to the baseline procedure. 
d. Patient has used oral steroids, budesonide or other sinus steroid irrigations/rinses, 
nebulized steroids administered nasally or budesonide drops during 14 days prior to 
the baseline procedure.
e.
Patient has oral-steroid dependent condition such as chronic obstructive pulmonary 
disease (COPD) or asthma.
f.
Patient has known history of allergy or intolerance to corticosteroids or 
mometasone furoate.
g. Patient has used monoclonal antibodies for asthma, allergies or nasal polyps (e.g., 
Dupixent, Nucala, Xolair) during 30 days prior to the baseline procedure.
h. Patient requires monoclonal antibodies for asthma, allergies or nasal polyps during 
the duration of the study.
i.
Patient has presence of physical obstruction that would preclude access and 
placement of the S8 Sinus Implant in the middle meatus (e.g., severe septal 
deviation, septal spur, very small middle meatus, total obstruction of the sinonasal 
passage with severe adhesion, scarring, polypoid edema or polyps).
j.
Patient has known history of human immunodeficiency virus (HIV) or 
immunoglobulin G or A subclass deficiency.
k. Patient has clinical evidence of acute sinusitis (AS), as defined in the 2016 
“International Consensus Statement on Allergy and Rhinology”. 
l.
Patient has clinical evidence or suspicion of invasive fungal sinusitis (e.g., bone 
erosion on prior computed tomography (CT) scan, necrotic sinus tissue).
m. Patient has evidence of severe concomitant disease or condition expected to 
compromise survival or ability to complete assessments during the 365-day study 
follow-up period (e.g., cancer).
n. Patient is currently participating in another clinical study. 
o. Patient has previously undergone ESS and experienced a cerebrospinal fluid (CSF) 
leak or has residual compromised vision as a result of a complication in a prior ESS 
procedure. 
p. Patient has known dehiscence of the lamina papyracea.
q. Patient has evidence of active tuberculosis or active viral illness (e.g.,  ocular herpes 
simplex, chickenpox, measles).
r.
Patient has known history or diagnosis of glaucoma or ocular hypertension (prior 
ocular exam with intraocular pressure of >21 mmHg and pressure lowering 
medication given) or posterior subcapsular cataract.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 24 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
10.3 Subject Withdrawal
Study subject may be withdrawn or terminated for the following reasons:

Subject death

Concomitant disease or any disease or condition that makes further study participation 
impossible (but without relationship to the investigational product). 

Subject voluntarily chooses not to participate further in the study. If withdrawal takes 
place after baseline procedure, the implants will be removed, if still present.

Subject’s non-compliance with study procedures.

Lost to follow-up: the subject is more than 30 days late to a study visit and three 
documented attempts to contact the subject are unsuccessful. A subject who misses a 
study visit should be contacted by site personnel to determine the reason for the missed 
visit, which should be documented in the subject’s study records. Note: A subject who 
misses a study visit but attends a subsequent visit will no longer be considered lost to 
follow-up.

In the investigators’s opinion, a significant safety concern arises that requires subject 
discontinuation.

In the investigators’s opinion, it is not in the best interest of the subject to continue 
study participation. The implants will be removed, if still present.
If a subject decides to withdraw from the study, every attempt should be made to continue to 
collect safety data in the patient’s medical records. Data collected up to the point of subject 
withdrawal or termination will be maintained in the study database and included in analyses as 
appropriate.
All enrolled subjects, including those withdrawn or lost to follow-up, will be accounted for and 
documented.
11
SUBJECT TREATMENT AND STUDY PROCEDURES 
11.1 Screening Phase 
Pre-screening
During the pre-screening phase, investigators or designees will perform an initial evaluation of 
potential candidates for study eligibility. This initial pre-screening phase may include review of 
existing patient information (e.g., previously performed diagnostic measures, medical history, 
sinus endoscopies, sinus surgery). 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 25 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Consent, screening and enrollment
If the patient appears to be a potential candidate for the study based upon existing information, 
written informed consent will be obtained. No protocol required testing will be performed solely 
for the purposes of this study prior to obtaining patient written informed consent. 
Investigators or designees will approach the patient to obtain written informed consent. The 
background of the proposed study, the implant procedure, the follow-up schedule and all 
potential risks and benefits will be carefully explained to each patient. The investigator or 
designee obtaining the informed consent shall:

Avoid any coercion of or undue influence of patients to participate,

Not waive or appear to waive patient’s legal rights,

Use language that is non-technical and understandable to the patient, and

Provide ample time for the patient to consider participation.
Each patient must sign and date the informed consent form (ICF) approved by an appropriate 
IRB and the sponsor. Patients are considered enrolled in the study upon signing the IRB-
approved ICF. Enrolled subjects will be assigned unique identifying codes by an Electronic 
Data Capture (EDC) system and entered into the study database.
The screening assessment will include an endoscopic examination, which will be recorded (see 
Section 5 Study Flow Diagram and Section 6 Schedule of Assessments). In addition, female 
subjects of reproductive potential must confirm their nursing status and undergo a urine 
pregnancy test and be informed about acceptable birth control methods. If the screening visit 
occurs on the same day as the baseline/procedure visit, all assessments will be recorded in the 
baseline visit forms.
All subjects who do not pass the screening assessment will be considered as screen failures and 
will be terminated from the study. The reason for ineligibility will be recorded in the EDC. 
11.2 Baseline/Procedure Phase
Baseline assessment
Upon meeting eligibility requirements, subjects will come in for an in-office baseline 
assessment, consisting of:

Nasal obstruction/congestion questionnaire,

SNOT-22 questionnaire, and

Endoscopic grading and video recording.
Female subjects of childbearing potential will undergo a urine pregnancy test prior to the 
baseline procedure and be required to use acceptable contraceptive method(s) during the entire 
duration of the study follow-up. Acceptable methods of contraception may include:

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 26 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.

Established use of oral, injection or implantables hormonal contraceptives; 

Double-barrier methods (i.e., intra-uterine devices) and barrier contraceptives (e.g., 
condom, diaphragm or cervical/vault caps) used with spermicide (foam, gel, film, 
cream or suppository); 

Female sterilization (e.g., tubal occlusion, hysterectomy or bilateral salpingectomy); or

Vasectomized male partner, if the sole partner for the subject.
Note: The baseline assessment of symptoms and pregnancy testing must be performed before 
implant procedure.
Subject preparation for baseline procedure
Subjects will be prepared for the baseline procedure per investigator’s standard protocol used 
for nasal endoscopy. The topical anesthesia regimen may consist of: 

Spraying the nasal cavity with 4% lidocaine (or equivalent, such as pontocaine) with 
oxymetazoline (or equivalent) nasal decongestant spray;

Placing cotton pledgets soaked in lidocaine (or equivalent) and oxymetazoline (or 
equivalent) solution against the inferior turbinate, and into the ethmoid sinus (if 
available in the clinic setting, topical cocaine may be used); and

Injecting into the sinus tissue and/or polypoid tissue with lidocaine (or equivalent) as 
necessary.
The anesthesia period should be as long as necessary to ensure complete numbness of the 
subject’s septum and middle turbinate. Once properly anesthetized, subjects may undergo the 
baseline procedure.
Baseline procedure
Subjects will undergo in-office bilateral placement of the S8 Sinus Implant in the ethmoid 
sinuses (total of two implants). The S8 Sinus Implant will be provided by sponsor and must be 
placed according to the prescribing information. 
No other procedures (e.g. polypectomy or balloon sinuplasty) are allowed at the time of the 
baseline procedure.
Implant disposal
The crimper and delivery system must be disposed per standard institutional practices for 
biohazard waste. If the S8 Sinus Implant, delivery system or other system components are 
associated with a device-related adverse event (AE), malfunction or failure, all the components 
should be returned to sponsor for evaluation, when possible. For the return of biohazard 
product, sponsor must be contacted prior to product return for handling instructions.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 27 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Implant removal
The S8 Sinus Implant is made from bioabsorable polymers designed to gradually soften over 
time. The implant may be left in the sinus to gradually release the corticosteroid over 
approximately 90 days. It must be removed by 90 days or may be removed earlier at the 
investigator’s discretion, using standard surgical instruments. As the implant softens over time 
and the polyps decrease, the implant may expel out of the nose on its own or with actions such 
as sneezing or forceful nose blowing. 
Implant malfunction
All potential implant malfunctions and any associated AEs will be recorded in the 
corresponding CRFs in the EDC system. All instances of suspected implant malfunction will be 
reviewed by the sponsor.
11.3 Follow-Up Phase
The follow-up period begins immediately post-procedure (once the patient exits the clinic). 
Each subject will return for up to 7 follow-up visits (see Section 5 Study Flow Diagram and 
Section 6 Schedule of Assessments).

Day 30 (± 7 days)

Day 60 (± 7 days)

Day 90 (± 7 days) – implant removal & repeat implant placement 

Day 120 (± 7 days)

Day 150 (± 7 days) 

Day 180 (± 14 days) – implant removal, as applicable

Day 365 (± 14 days)
The protocol-required follow-up assessment at each visit through Day 180 will consist of:

Nasal obstruction/congestion questionnaire,

SNOT-22 questionnaire, and

Endoscopic grading and video recording.
Repeat implant placement procedure at Day 90
At the Day 90 follow-up visit, subjects with ethmoid sinuses with polyps (grade ≥1) will 
undergo repeat implant placement unilaterally or bilaterally. Repeat implant placement must not 
be performed in the ethmoid sinuses with no nasal polyps (grade <1). All implants placed at 
Day 90 must be removed at Day 180 or may be removed earlier at the investigator’s discretion.
If polypectomy is performed at the Day 90 follow-up visit, polyp grading must be done after 
polypectomy to qualify a given subject for repeat placement of the S8 Sinus Implant. 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 28 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Note: The assessment of symptoms and pregnancy testing must be performed before repeat 
implant placement procedure.
Unscheduled visits
Subjects may come in for additional unscheduled office visits if necessary. Circumstances that 
may warrant additional visits include but are not limited to: 

Worsening of sinus symptoms,

Sinus-related adverse events requiring medical evaluation, and/or 

Implant migration
The assessment at an unscheduled visit will consist of:

Nasal obstruction/congestion questionnaire,

SNOT-22 questionnaire, and

Endoscopic grading and video recording.
12
CONCOMITANT MEDICATION
The study standardized medication regimen will be as follows:

Leading up to the baseline procedure, there is a 30-day restriction for use of parenteral 
and injected steroids (e.g., Kenalog injection), and monoclonal antibodies (e.g., 
Dupixent, Nucala, Xolair) 1

Leading up to the baseline procedure, a 14-day restriction for use of oral steroids, 
budesonide or other sinus steroid irrigations/rinses, nebulized steroids administered 
nasally or budesonide drops. 

After the baseline procedure, subjects will be encouraged to use saline rinses regularly 
through Day 365. 

After the baseline procedure, subjects will be required to use MFNS 200 mcg (two 
sprays in each nostril) once daily throughout the entire duration of the follow-up, unless 
the use of MFNS is not warranted clinically. Both the generic version of MFNS by 
Apotex or Novartis and the brand-name version by Merck (Nasonex) can be used. 

High-dose steroids (e.g., oral, parenteral, injections, budesonide or other sinus steroid 
irrigations, rinses or drops, nebulized steroids administered nasally) will be allowed 
during the study follow-up only if clinically necessary (see Section 13 Medical and 
Surgical Interventions).

Orally-inhaled steroids for control of asthma will be permitted.

If infection is suspected at any time during the study, treatment with antibiotics will be 
permitted.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 29 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.

Use of monoclonal antibodies is prohibited during the 365-day follow-up period.

To the extent possible, subjects will be maintained on stable regimens of leukotriene 
inhibitors and/or immunotherapy (e.g., Montelukast, Zafirleukast, Zileuton) for 
allergies through Day 365, if currently on such regimens; however, use of breath-
powered or other methods of intranasal steroid delivery for allergies is not permitted 
during the study.

Use of drug-eluting implants (PROPEL®, PROPEL® Mini, PROPEL® Contour) is 
prohibited during the baseline procedure and throughout the 365-day follow-up period, 
unless placed immediately following RESS performed in the operating room setting.
All sinus-related and AE-related medications will be recorded in EDC, including their full 
brand/trade or generic names (whichever prescribed), dose, frequency, indication, start and end 
dates. Each AE will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and presented based on the system organ class (SOC) and preferred term.
13
MEDICAL AND SURGICAL INTERVENTIONS
Subsections below describe the rescue treatments consisting of medical and surgical 
interventions that will be allowed during the study follow-up based upon subject’s symptomatic 
and endoscopic outcomes.
13.1 Medical Intervention
During study follow-up, high-dose steroids (e.g., oral, parenteral, injection, budesonide or other 
sinus steroid irrigations, rinses or drops, nebulized steroids administered nasally) may be used 
as a medical intervention in cases where a clinically significant increase or persistence in 
ethmoid sinus polyposis occurs, coupled with subject complaint of sinusitis symptoms that 
cause subject to request intervention. 
If oral steroids are required for reasons other than, and not including, ethmoid sinus polyposis, a 
regimen is allowed. In either case, oral steroid intervention will be noted on the medication and 
follow up CRFs (see Section 16.5 Handling Steroid or Surgical Interventions). 
13.2 Surgical Intervention
During study follow-up, surgical intervention (e.g., in-office polypectomy, RESS) may be 
required in cases where a clinically significant increase or persistence in ethmoid sinus 
polyposis occurs, coupled with subject complaints of sinusitis symptoms that cause subject to 
prefer sinus surgery. 
Note: Subjects requiring medical or surgical interventions will be followed through the end of 
the study.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 30 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
14
ASSESSMENT OF SAFETY
14.1 Specifications of Safety Parameters
Adverse events for each subject from the time the subject gives informed consent through Day 
365 (end of study) will be recorded in EDC and monitored. Each AE will be evaluated by 
investigators in terms of seriousness, severity (i.e., mild, moderate, severe) and strength of 
relationship (i.e., not related, unlikely related, possibly related, related) to study drug, study 
device, and implant procedure. Each AE will be reviewed by sponsor personnel or contractors. 
The study sponsor is responsible for ensuring that all AEs are appropriately recorded and, when 
applicable, reported to the government(s), ethics committee(s) and other study centers per 
applicable regulations.
Subjects may experience a persisting set of symptoms associated with CS with nasal polyps and 
continue to present with symptoms during the timeframe after the baseline procedure. These 
may include symptoms such as facial pain or discomfort, headache, return of sense of smell, 
crusting, or epistaxis. Subjects with CS may also suffer from acute infectious and/or 
inflammatory exacerbations unrelated to the implant due to the natural course of their chronic 
sinusitis. Therefore, investigators should evaluate the occurrence of adverse events in this 
population with CS with the natural course of the disease in mind. Findings such as crusting, 
polyp persistence/formation or middle turbinate lateralization will not be considered as AEs 
since they are captured on the endoscopic grading forms. 
14.2 Classification of Adverse Events
Severity of event
Sponsor will be responsible for determining whether an AE is expected or unexpected based on 
the nature, severity, or frequency of the event as previously described in the risk management 
documents for the investigational product. TEAE, SAE, SAR, SUSAR, UADE and USADEs 
are defined in Section 3 Definitions of Terms.
Relationship of adverse event
An adverse event related to the use of study implant, which includes AEs resulting from 
insufficient or inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device. This also includes any 
event resulting from user error or from intentional misuse of the implant. [BS EN ISO 14155]
Based on the 21 CFR 312 and BS EN ISO 14155, the relationship of all AEs to the implant will 
be categorized into: 

Related: There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs in a plausible time relationship to drug administration and 
cannot be explained by concurrent disease or other drugs or chemicals. The response to 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 31 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
withdrawal of the drug (dechallenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically definitive.

Possibly-related: There is some evidence to suggest a causal relationship (e.g., the 
event occurred within a reasonable time after administration of the trial medication). 
However, other factors may have contributed to the event (e.g., the participant’s clinical 
condition, other concomitant events). Although an AE may rate only as “possibly 
related” soon after discovery, it can be flagged as requiring more information and be 
updated, as appropriate.

Unlikely-related: A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to drug administration makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after administration of the trial 
medication) and in which other drugs or chemicals or underlying disease provides 
plausible explanations (e.g., the participant’s clinical condition, other concomitant 
treatments).

Not-related: The AE is completely independent of study drug administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the investigator. 
Any AE that is determined by a participating investigator to be directly related (related and 
possibly-related) to the implant-procedure, device, or drug will be categorized as implant-
related.
For implant-related AE (anticipated or unexpected/unanticipated), sponsor may request source 
documentation to confirm the relationship of the AE/SAR to the implant and may review such 
AE with an independent otolaryngologist, as needed. 
Note: The occurrence of a diagnostic or elective surgical procedure for a pre-existing condition, 
unless the condition becomes more severe or increases in frequency, would not be considered 
implant-related.
Severity of adverse event
Severity of AEs will be graded per 21 CFR 312 as follows:

Mild: If an AE requires minimal or no treatment and does not interfere with the 
participant’s daily activities.

Moderate: If an AE results in a low level of inconvenience or concern with the 
therapeutic measures. Moderate AEs may cause some interference with functioning.

Severe: If an AE interrupts a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe AEs are usually potentially life-threatening or 
incapacitating.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 32 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
14.3 Guidelines for Reporting of Adverse Events
Adverse event reporting
All AEs, regardless of seriousness or relationship to the implant, will be recorded in EDC and 
will include event description, date of onset, investigator’s assessment of severity, relationship 
to investigational product, and date of resolution/stabilization of the event. All AEs occurring 
while on study must be documented appropriately regardless of relationship. All AEs will be 
followed through end of the study.
Any preexisting medical condition that is present at the time of screening will not be reported as 
an AE. The occurrence of a diagnostic or elective surgical procedures for a pre-existing 
condition will not be recorded as an AE, unless the condition become more severe or results in 
an AE
Whenever possible, diagnosis or single syndrome should be reported instead of symptoms. The 
investigator should specify the date of onset, severity, action taken with respect to implant, 
corrective treatment/therapy given, additional investigations performed, outcome, and his/her 
opinion as to whether there is a reasonable possibility that the AE was caused by the implant.
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode.
The investigator should take appropriate measures to follow all AEs until resolution or until 
progression has been stabilized, to ensure the safety of the subjects. If the AE continues beyond 
the last planned visit per protocol, investigators should follow the subjects until AE resolution; 
stabilization and safety data will be recorded in the patient medical records.
When subject participation is prematurely discontinued, every attempt should be made to 
continue to collect safety data in the patient’s medical records. 
Serious adverse event reporting 
All AEs that meet the criteria of an SAE must be reported to the sponsor based on the following 
timeline: 
Type of Report
Reporting Schedule
Serious adverse event or Serious 
Suspected Adverse Reaction
Within 24 hours after becoming aware
The investigator will report the above to the reviewing IRB per the IRB’s guidelines.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 33 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
All SAEs will be followed until satisfactory resolution; until the investigator deems the event to 
be chronic or the adherence to be stable. Other supporting documentation of the event may be 
requested by the sponsor and should be provided as soon as possible. 
Drug and device serious adverse event reporting
The study sponsor is responsible for conducting an evaluation of all ADE/SAR throughout the 
study duration. Since S8 Sinus Implant is a single-entity combination product, the sponsor shall 
report to the FDA all device-related UADE within 10 working days and all SAE and SUSAR 
within 15 calendar days after the sponsor deems the adverse event to be reportable. Sponsor is 
also responsible to notify all reviewing IRBs and participating investigators within 10 days after 
such determination is made. Thereafter the sponsor shall submit any additional reports 
concerning the effect as FDA requests. The sponsor will notify FDA of any unexpected fatal or 
life-threatening AE/SAR as soon as possible but in no case later than 7 calendar days after the 
sponsor’s initial receipt of the information.
15
SAFETY INSTRUCTIONS
15.1 Contraindications
The S8 Sinus Implant is contraindicated in patients with:

Suspected or confirmed intolerance to mometasone furoate.

Known hypersensitivity to lactide, glycolide, or caprolactone copolymers
15.2 Warnings and Precautions
Refer to Section 5 of the S8 Sinus Implant Package Insert.
15.3 Adverse Reactions
Adverse reactions from placement of the S8 Sinus Implant may include:

Epistaxis

Nasal discomfort

Facial pain 

Headache

Parosmia

Nasal odour

Eye irritation 

Dizziness

Rhinalgia 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 34 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.

Presyncope

Nasal congestion
Refer to Section 6.2 of the S8 Sinus Implant Package Insert for additional potential risks or 
adverse events.
Risks relating to the insertion and removal procedure
Risks associated with the insertion and removal of the S8 Sinus Implant are similar to those 
associated with other endoscopic sinus procedures. These potential risks include:

Facial pain, nasal pain or discomfort related to the use of topical or local anesthetic 
medications

Vasovagal reaction associated with the application of topical or local anesthetic 
medications

Facial pain, nasal discomfort or pain, minor oozing or bleeding related to suctioning, 
manipulation of polyps, lysis of adhesions related to insertion or removal of the implant

Injury to the middle turbinate or other structures of the middle meatus or ethmoid sinus

Injury to nerves or blood vessels

Infection at the insertion site

Implant migration from its intended location in the sinus in which it was placed
15.4 Patient Counseling
For best results, subjects will be advised as follows: 

To use nasal saline sprays or irrigations

That the implant is bioabsorbable and intended to soften over time. As the implant 
softens and polyps decrease, the implant may be expelled out of the nose on its own or 
with actions such as sneezing or forceful nose blowing.

To call the study investigator immediately if they experience any of the following:

Excessive nasal bleeding or symptoms of infection, such as excessive pain or 
discomfort, persistent headache, increased sinus discharge.

Symptoms suggesting the implant has migrated posteriorly, such as irritation or 
choking sensation in the back of the throat.
15.5 Potential Benefits from Study Participation
There may be no direct benefits from participating in the study. However, study patients will 
undergo an enhanced level of clinical scrutiny compared to routine clinical care for chronic 
sinusitis, which may provide some indirect health benefits. 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 35 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
When placed in post-ESS patients with symptoms of recurrent nasal obstruction, the implant is 
intended to provide an immediate onset of action by dilating the sinus tissue, creating an 
opening in the middle meatus and ethmoid sinus, providing for ventilation, drainage and 
reducing the perceived sensation of nasal obstruction/congestion. The addition of mometasone 
furoate to the implant is intended to reduce inflammation and polyps. Patients may benefit from 
these actions. 
16
STATISTICAL CONSIDERATIONS
A formal Statistical Analysis Plan (SAP) will be prepared prior to the study database lock and 
formal data analysis. Following is a summary of the intended analyses.
16.1 Sample Size Calculation
The 50-patient sample size was selected based on clinical judgment. Based on the RESOLVE II 
study (data on file at Intersect ENT Inc.), ~90% of sinuses had polyps of grade 1 or higher at Day 
90. Based on this data, of the 100 sinuses that undergo implant placement at baseline, greater than 
85 sinuses are expected to undergo repeat placements at Day 90. This will provide safety data on 
up to 185 implant procedures (100 implants at baseline; 85 implants at Day 90), which is deemed 
to be a large enough sample to detect potential additional implant-related adverse events 
associated with recurrent use of the implant.
16.2 Analysis of Safety Measures
The incidence of AEs and SAEs through Day 365, including treatment emergent AEs (TEAE), 
implant-related AEs, UADE/USDAE, and SAR/SUSAR will be presented. 
16.3 Analysis of Efficacy Endpoints
Patient-reported outcomes 
Symptom scores and change from baseline in symptom scores will be summarized using 
descriptive statistics. Means, standard deviations (SD), medians, ranges and, where appropriate, 
95% CI for the mean assuming a normal distribution will be presented at each timepoint. 
Endoscopic outcomes
Endoscopic grades and change from baseline in endoscopic grades will be summarized using 
descriptive statistics. Means, standard deviations (SD), medians, ranges and, where appropriate, 
95% confidence intervals (CI) for the mean assuming a normal distribution will be presented at 
each timepoint.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 36 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
16.4 Analysis of Other Endpoints
Implant delivery success rate
Implant delivery success rate will be reported with descriptive statistics. The left and right sides 
of each patient will be considered independent, and each patient is expected to contribute up to 
4 observations: 2 implants at baseline; between 1 and 2 observations during follow-up 
(maximum of 1 repeat placements in each ethmoid sinus).
Interventions received
All interventions received for ethmoid sinus obstructions will be tabulated and reported with 
descriptive statistics.
16.5 Handling Steroid or Surgical Interventions
Use of high-dose steroids (e.g., oral, parenteral, injection, budesonide or other sinus steroid 
irrigations or drops, nebulized steroids administered nasally) or surgical intervention during the 
study will be recorded and tabulated. 
Note: Repeat S8 Sinus Implant at the protocol-specified Day 90 visit does not constitute a high 
dose steroid intervention. 
16.6 Analysis Populations
All analyses will be conducted using the safety population defined as all subjects and sinuses 
that actually received the S8 Sinus Implant in a target sinus at baseline.
17
STUDY MANAGEMENT
17.1 Ethical Considerations
The rights, safety and well-being of subjects shall be protected in accordance with the ethical 
principles described in the Declaration of Helsinki. All parties are responsible for ethical 
conduct of the study in accordance with their respective roles in the investigation. The sponsor 
and the investigator(s) shall avoid improper influence or inducement of the study subject, 
monitor, the clinical investigator(s) or other parties participating in or contributing to the 
clinical investigation. 
17.2 Sponsor Responsibilities
Intersect ENT, as the study sponsor, has the overall responsibility for the conduct of the study 
and will ensure that the study is conducted under the guidance of ICH Good Clinical Practice, 
Clinical investigation of medical devices for human subjects – Good clinical practice (BS EN 
ISO 14155: 2011) and other applicable local and federal (e.g., 21 CFR Parts 11, 50, 56, 312 and 
812) regulations, including the archiving of essential documents. Qualified personnel who 
participate in the conduct of this clinical trial will be qualified by education and/or experience to 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 37 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
perform their tasks. Intersect ENT will not use, in any capacity, the services of any person 
debarred under section 306 of the Federal Food, Drug, and Cosmetic Act in connection with this 
clinical study. 
17.2.1 Training
Sponsor personnel or designee will provide all investigators and sub-investigators with training 
on use of the S8 Sinus Implant prior to their participation in the clinical study.
The study center staff involved will undergo site initiation and training which will include: 

Study protocol

Consenting procedures

Package Insert

Investigator responsibilities, including reporting requirements 

CRF completion guidelines

EDC system

Endoscopic grading scales, recording and video uploading.

Investigational product accountability procedures

Protection of subject confidentiality
17.2.2 Protocol Deviation
Any deviation from the requirements outlined in this protocol will be considered a protocol 
deviation. A protocol deviation that may affect the scientific soundness of the protocol or the 
rights, safety, or welfare of the patients should be reported to the sponsor and the Institutional 
Review Board or Ethics Committee as soon as possible. Other deviations are those that occur in 
direct association with a specific study patient. These include, but are not limited to, deviations 
from the informed consent process, inclusion/exclusion criteria, protocol-specified procedures 
and assessments, and investigational product handling and usage. All efforts should be made to 
avoid any protocol deviation.
17.2.3 Monitor Responsibilities
Study site monitoring will be performed by Clinical Research Associates (CRAs) from sponsor 
and contract CRAs who will be trained by sponsor. Study sites will be visited regularly to 
ensure that the study is conducted in compliance with 21 CFR Parts 50, 56, 312, 812, the study 
protocol and other applicable regulations. Study monitors will also ensure that the data reported 
in the Electronic Data Capture (EDC) system is consistent with the information found in the 
subject’s medical records and source documents (source data verification). Monitoring will 
include assessment of the site’s overall progress, including but not limited to the site’s ability to 
keep accurate records and to report study related data, including AEs, to the study sponsor in a 
timely fashion. 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 38 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
17.2.4 Data Management Responsibilities
Data management will be performed by sponsor.
Electronic data capture (EDC)
An EDC system will be utilized to capture study data and compliant with 21 CFR Part 11 and 
under the guidance of ‘FDA Guidance for Industry: Computerized Systems Used in Clinical 
Investigations’. Data entry will be performed by site personnel after completing an appropriate 
training. Modifications to the EDC will be made if deemed necessary by the study sponsor.
Data cleaning
The database will be subject to initial inspection for omitted data, gross data inconsistencies, 
and deviations. Any deficiencies or deviations will be reviewed and any necessary action 
determined (e.g., data query, communication with the study center). 
Intermittent data review will be performed and any discovered errors will be reported to the 
study site using the electronic query process (as necessary). The study site will be expected to 
review and complete the query. The data cleaning cycle will be repeated until all data are 
considered clean.
Data back-up, confidentiality and security
Incremental data back-up will be performed on a regular basis by the EDC system vendor. All 
media will be stored in a secure location. Passwords will be issued to appropriate personnel to 
ensure confidentiality and protection of data. 
17.2.5 Investigational Product Accountability
An appropriate number of the investigational product, S8 Sinus Implants, will be provided to 
the study sites. The sites maintain the investigational product in a locked, secure location. Only 
investigators participating in the study will have access to the investigational product. 
Dispensing of investigational product will be documented by authorized personnel. Each batch 
of the investigational product will be assigned a serial/lot number for tracking purposes.  
Investigational product inventory logs are maintained by site personnel. These logs are 
reconciled prior to study closure. Any unused inventory of the investigational product will be 
returned to sponsor at the direction of the sponsor or at the close of the study.  
17.3 Investigator Responsibilities
General responsibilities

Each investigator is responsible for ensuring that an investigation is conducted per the 
signed investigator statement (form FDA1572), the study protocol, and applicable 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 39 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
regulations; for protecting the rights, safety, and welfare of study participants under the 
investigator’s care; and for the control of drugs under investigation.

Each investigator shall, obtain informed consent of each patient to whom the treatment 
is administered in accordance with provisions of 21 CFR part 50. 

Each investigator is responsible for all applicable IRB requirements under 21 CFR part 
56.

Each investigator and sub-investigators are responsible for disclosure of financial 
obligations to the sponsor.

To ensure proper execution of the study protocol, each investigator will identify a study 
coordinator for this study. Working with and under the authority of the investigator, the 
study coordinator assures that all study requirements are fulfilled, and is the contact 
person at the site for all aspects of study administration. 

Each investigator will allow auditing of their clinical investigation procedure(s) by the 
sponsor or designee.
Control and disposition of the investigational product
An investigator shall administer the product only to patients under the investigator’s personal 
supervision or under the supervision of a sub-investigator responsible to the investigator. The 
investigator shall not supply the investigational product to any person not authorized to receive 
it. An investigator is required to maintain adequate records of the disposition of the product, 
including dates, quantity, and use by patients. All unused product must be returned to sponsor.
Maintenance of study records
Each investigator is required to prepare and maintain adequate and accurate case histories that 
record all observations and other data pertinent to the investigation on each subject participating 
in the investigational plan (including information maintained electronically such as digital 
imaging). The investigator will also maintain original source documents from which study-
related data are derived, which may include, but are not limited to:

Clinic progress notes recording patient’s medical history and medications

Medical charts with operative reports and condition of patient upon discharge

Medical records regarding AEs, including treatment and clinical outcome 

Results of diagnostic examinations

Imaging records such as x-rays, CT scans and video-endoscopies and associated reports 
(hard copy and digital copy of images, as available)

Notes of phone calls and/or correspondence indicating study center’s attempts to follow 
study patients at the required follow-up visits until their participation in the study is 
complete or terminated

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 40 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.

Records relating to subject deaths (e.g., death certificate, autopsy report)

Printouts of source data generated by technical equipment (e.g., CT, endoscopy, MRIs) 
must be filed with the subject’s records. 

Video of endoscopic procedures (screening, treatment and follow up assessments).
An investigator shall retain records required to be maintained for a period of two years 
following the date a marketing application is approved for the drug for the indication for which 
it is being investigated. If no application is to be filed, records shall be retained for two years 
after the investigation is discontinued and FDA is notified. To avoid error, the study site should 
contact the study sponsor prior to the destruction of study records to ensure that they no longer 
need to be retained. In addition, sponsor should be contacted if the investigator plans to leave 
the study center, so that arrangements can be made for the handling or transfer of study records, 
or if the records are moved to an off-site location.
Required documents from study centers
At a minimum, the following documents will be provided by the study center to the study 
sponsor:

IRB study approval letter 

IRB approved informed consent 

fully executed clinical trial agreement (CTA)

signed statement of investigator (form FDA 1572)

financial disclosure form for the participating investigator(s)

curriculum vitae (CV) for the participating investigator(s)

current medical license for the participating investigator(s)

principal investigator protocol acknowledgement form 
A site may not begin active enrollment of patients until the documentation for the site principal 
investigator has been provided to sponsor and an initiation visit has been performed.
17.4 Protection of Subject Confidentiality
In all clinical studies, confidentiality of protected health information may be breached due to 
study-related activities beyond those of routine clinical care. This risk will be minimized by not 
collecting personally identifying information on CRFs or other study related documentation to 
be provided to the study sponsor. It is the sponsor’s policy to redact any subject’s personally 
identifying information from any documentation sent to Sponsor that inadvertently contains it.
At all times throughout the clinical investigation, confidentiality will be observed by all parties 
involved. All data shall be secured against unauthorized access. Privacy and confidentiality of 
information about each subject shall be preserved in the reports and in any publication. Each 
subject participating in this study will be assigned a unique identifier. All database forms and 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 41 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
source documents sent to the sponsor will be tracked, evaluated, and stored using only this 
unique identifier. 
Investigators will maintain confidential study subject lists identifying all enrolled subjects. The 
investigators bear responsibility for keeping these lists current and confidential. These lists will 
not be provided to the study sponsor.
Monitors and auditors will have access to the study screening and enrollment logs and other 
personally identifying information of study subjects to ensure that data reported in the EDC 
corresponds to the person who signed the ICF and the information contained in the original 
source documents. Such personal identifying information may include, the subject’s name, 
address, date of birth, gender, race and medical record number. 
The subject’s name, medical record number or address will not be recorded in the monitor’s 
visit report or the database. Demographic data that may be recorded include age, race and 
gender. 
Any source documents copied for monitoring purposes by the sponsor will be identified by 
using the assigned subject’s unique identifier in an effort to protect subject confidentiality. All 
personally identifiable information will be redacted from source documents.
17.5 Study Suspension or Early Termination
The study can be discontinued at the discretion of the investigator or study sponsor for reasons 
including the following:

Occurrence of AE unknown to date in respect to their nature, severity, or duration, or 
the unexpected incidence of known AE

Obtaining new scientific knowledge that shows that the study is no longer valid or 
necessary

Insufficient recruitment of subjects

Investigational drug presents an unreasonable and significant risk to subjects (sponsor 
may terminate the study immediately)

Persistent non-compliance with the study protocol

Persistent non-compliance with the applicable ethics committee or regulatory 
requirements
If the study is discontinued or suspended prematurely, the sponsor shall promptly inform all 
clinical investigators and study centers of the termination or suspension and the reason(s) for 
termination. The IRB shall also be informed promptly and provided with the reason(s) for the 
termination or suspension by the sponsor or by the clinical investigator and/or investigation 
centers. Regulatory authorities and the subject’s physicians may also need to be informed, if 
deemed necessary.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 42 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
17.6 Site Closeout
At the time of the site close-out visit, the monitor will have ensured all outstanding study 
documents are reconciled, the investigator’s files are accurate and complete, have reviewed 
record retention requirements with the investigator, made a final accounting of all study 
supplies, and ensured that all applicable requirements are met for the study (this visit will be 
conducted according to the study sponsor’s SOP for close-out visits). Any specific observations 
and actions made at this visit may be documented in a final report.
17.7 Quality Assurance and Supervision by Authorities
All documents and data shall be produced and maintained in such a way to assure control of 
documents and data to protect the subject’s privacy as far as reasonably practicable. The 
sponsor and representatives of the FDA or other regulatory authorities are permitted to inspect 
the study documents (e.g., study protocol, CRFs, and original study-relevant medical 
records/files) as needed. All attempts will be made to preserve subject confidentiality.
The study centers are subject to audit by study sponsor personnel or designee for protocol 
adherence, accuracy of CRFs and compliance with applicable regulations. The sponsor will 
communicate to the sites any patterns of non-compliance. The sponsor will work with the sites 
to determine any necessary corrective action, as applicable. The sponsor will continue to 
monitor sites until compliance has been secured. If the site continues to display non-
compliance, more serious action may be taken by the sponsor. The study protocol, data-
recording procedures, data handling and study reports are subject to an independent clinical 
Quality Assurance audit by sponsor, its designee, or health authorities.
Approved informed consent form: protection of study subjects
An IRB must review and approve an ICF specific to this study. Sponsor will provide an 
example ICF. The site, to meet specific requirements, may modify this example ICF; however, 
the ICF must contain all of the elements required by sponsor. IRB approved ICF and renewed 
approvals as appropriate will be maintained by the site for the duration of the study. The 
original, signed and dated ICF for each subject should be maintained by the site for monitoring. 
Subjects will be informed both verbally and in writing (i.e., ICF) about the nature of the study, 
the anticipated risks and benefits involved and the discomfort to which they will be exposed. 
They will be instructed about their right to discontinue their participation at any time without 
prejudice or jeopardy to future medical care. They must confirm consent in writing prior to any 
screening procedures. A copy of the informed consent form will be provided to the subject.
Institutional review board approval
IRB approval of study protocol and ICF is required prior to study commencement under 21 
CFR Part 56. Investigators must also obtain renewal of IRB approval throughout the duration of 
the study. Investigators are responsible for fulfilling any conditions of approval imposed by the 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 43 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
reviewing IRB, such as regular reporting, study timing, etc. Investigators will provide the study 
sponsor with copies of such approvals and reports.
Other investigator reports
Investigators are responsible for notifying the sponsor of the following:
Type of Notification
Timeline
Withdrawal of IRB Approval
Within 24 hours of becoming aware
Informed Consent not Obtained
Within 24 hours of becoming aware
Notifications must identify subjects using the unique study identifier to protect subject’s 
confidentiality.
17.8 Final Clinical Study Report
A final clinical study report (CSR) will be prepared by the study sponsor and provided to the 
regulatory agency. 
17.9 Publication Policy
At the completion of the study, an abstract reporting the results will be prepared and may be 
presented at scientific meeting(s). A manuscript may also be prepared for publication in a peer-
reviewed scientific journal. The principal investigators may publish results of the study; 
however, the study sponsor will be allowed 60 days to review the manuscript prior to 
submission, to ensure protection of intellectual property.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 44 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
18
APPENDIX 
Appendix A. List of medications considered as high-dose steroids
Trade Name
(alphabetic order)
Generic Name
Route of Administration
Budesonide
Pulmicort Respules
Prednisone (Budesonide)
Budesonide
Nasal (e.g., irrigations, rinses)
Dexamethasone
Dexamethasone
Intramuscular
Oral
Decadron
Dexamethasone
Dexamethasone
Intravenous or oral 
Nasal irrigations/rinses
Depo Medrol
Medrol
Medrol Dosepak 
Methylprednisolone
Methylprednisolone
Methylprednisolone Acetate
Oral 
Parenteral routes (e.g., intra-
articular, intra-cervical)
Fluticasone 
Fluticasone Propionate
Fluticasone Propionate w/Salmeterol
Nasal irrigations
Kenalog
Triamcinolone
Triamcinolone Acetonide
Intramuscular
Subcutaneous
Submucosal
Prednisone
Prednisone
Intramuscular
Oral 
Note for CRAs, data managers, biostatisticians: The above table is for reference purposes only and not a 
comprehensive list. Any questionable cases should be reviewed individually. 

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 45 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
19
REFERENCES
Bhattacharyya N, Orlandi RR, Grebner J, Martinson M. Cost burden of chronic rhinosinusitis: 
A claims-based study. Otolaryngol HNS. 2011, 144(3):440-45.
Blackwell DL, Lucas JW, Clarke TC. Summary health statistics for U.S. adults: national health 
interview survey, 2012. Vital Health Stat 10. 2014, 260:1-161.
Caulley L, Thavorn K, Rudmik L, et al. Direct costs of adult chronic rhinosinusitis by using 4 
methods of estimation: Results of the US Medical Expenditure Panel Survey. J Allergy Clin 
Immunol. 2015, 136(6):1517-22.
DeConde AS, Mace JC, Levy JM, et al. Prevalence of polyp recurrence after endoscopic sinus 
surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2016, 127(3):550-55.
Fandino M, Maconald K, Lee J, Witterick I. The use of postoperative topical corticosteroids in 
chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis. Am J Rhinol 
Allergy. 2013, 27(e146-e157).
Han JK. Subclassification of chronic rhinosinusitis. Laryngoscope. 2013, 123:S15-27.
Joe SA, Thambi R, Huang J. A systematic review of the use of intranasal steroids in the 
treatment of chronic rhinosinusitis. Otolaryngol HNS. 2008, 139(3):340-47.
Lavigne F, Miller SK, Gould AR, et al. Steroid-eluting sinus implant for in-office treatment of 
recurrent nasal polyposis: a prospective, multicenter study. Int Forum Allergy Rhinol. 2014, 
4(5):381-89.
Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and 
Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016, 6 Suppl 1:S22-S209.
Ow R, Groppo E, Clutter D, Gawlicka AK. Steroid-eluting sinus implant for in-office treatment 
of recurrent polyposis: a pharmacokinetic study. Int Forum Allergy Rhinol. 2014, 4(10):816-22.
Philpott C, Hopkins C, Erskine S, et al. The burden of revision sinonasal surgery in the UK-data 
from the Chronic Rhinosinusitis Epidemiology Study (CRES): a cross-sectional study. BMJ 
Open. 2015, 5(4):e006680.
Poetker DM. Oral corticosteroids in the management of adult chronic rhinosinusitis with and 
without nasal polyps: an evidence-based review with recommendations. Int Forum Allergy 
Rhinol. 2013, 3(2):104-20.
Sanan A, Rabinowitz M, Rosen M, Nyquist G. Topical therapies for refractory chronic 
rhinosinusitis. Otolaryngol Clin North Am. 2017, 50(1):129-41.
Santarelli GD, Han JK. Implantable Devices/Drugs in the Management of Nasal Polyps. Adv 
Otorhinolaryngol. 2016, 79:131-7.

Clinical Study Protocol P500-0717 (The ENCORE Study)
Doc # CP 00015 Rev. 2.0, October 12, 2017
CONFIDENTIAL 
Page 46 of 46
May not be reproduced outside of Intersect ENT without written permission from Document Control.
Sastre J, Mosges R. Local and systemic safety of intranasal corticosteroids. J Investig Allergol 
Clin Immunol. 2012, 22(1):1-12.
Wei C, Adappa N, Cohen N. Use of topical nasal therapies in the management of chronic 
rhinosinusitis. Laryngoscope. 2013, 123:2347-59.
Wu AW, Ting JY, Platt MP, et al. Factors affecting time to revision sinus surgery for nasal 
polyps: a 25-year experience. Laryngoscope. 2014, 124(1):29-33.
Wynn R, Har-El G. Recurrence rates after endoscopic sinus surgery for massive sinus 
polyposis. Laryngoscope. 2004, 114(5):811-3.