The ASCEND Study: A Clinical Evaluation of the UP Drug-Coated Device in Patients With Chronic Rhinosinusitis
Conditions: Chronic Rhinosinusitis (Diagnosis)
Sponsor: Intersect ENT

The ASCEND Study 
P500-0118, Rev. 8.0, 04 APR 2019 
 CONFIDENTIAL 
The ASCEND Study 
A Clinical Evaluation of the UP Drug-Coated 
Device in Patients with Chronic Rhinosinusitis 
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Senior Vice President Clinical and Medical Affairs 
Date 
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Boris Karanfilov, MD 
Principal Investigator 
Date 
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Clinical Study Protocol P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
CONFIDENTIAL 
1 of 55 
May not be reproduced outside of Intersect ENT without written permission from Document Control. 
CLINICAL STUDY PROTOCOL 
1 TITLE PAGE 
Study Title 
The ASCEND Study: A Clinical Evaluation of the UP Drug-Coated 
Device in Patients with Chronic Rhinosinusitis  
Protocol Number 
P500-0118 
Investigational Device 
UP Drug-Coated Device (mometasone furoate, 3000 mcg) 
Study Design 
Prospective, multicenter, clinical trial, enrolling patients into two 
consecutive cohorts: a PK cohort and a randomized, blinded, intra-
patient controlled cohort 
Sponsor’s Name and 
Address 
Intersect ENT, Inc. 
1555 Adams Drive 
Menlo Park, CA 94025 USA 
Tel:  +1 650-641-2100  
Fax: +1 650-641-2053 
National Principal 
Investigator 
Boris Karanfilov, MD 
Director, The Ohio Sinus Institute 
5378 Avery Road 
Dublin, OH 43016 USA 
 
Name and address of each participating clinical investigator will be 
maintained on file by Intersect ENT 
Data Management and 
Study Monitoring 
Intersect ENT, Inc. 
Biostatistics and Data 
Analysis 
Intersect ENT, Inc. 
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 
ISO 14155) and other applicable local and federal regulations, including the archiving of essential documents. 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is the property of Intersect ENT, Inc. 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 P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
CONFIDENTIAL 
2 of 55 
May not be reproduced outside of Intersect ENT without written permission from Document Control. 
Revision History: 
Revision 
Revision Date 
Summary of Changes 
1.0 
15 Feb 2018 
Initial release 
2.0 
23 Mar 2018 
• 
Renamed pilot to Randomized cohort 
• 
Increased sample size of Randomized cohort to 70 subjects 
and 10 study centers 
• 
Added language to allow dilation of the maxillary or sphenoid 
sinus with the same Sinus Dilation Device after successful 
dilation of both frontal sinuses, if necessary 
• 
Updated sample size justification, analysis of the primary 
efficacy endpoint, analysis of secondary endpoints, and 
sensitivity analysis for the primary efficacy endpoint 
• 
Added definitions of safety, intent-to-treat, and per-treatment-
evaluable populations 
• 
Added inclusion criteria to confirm bilateral obstruction of the 
FSO on endoscopy at baseline 
• 
Updated list of compatible devices 
• 
Several editorial changes for consistency throughout the 
protocol  
3.0 
05 Apr 2018 
• 
Corrected error in the flow diagram – number of subjects 
changed from N=50 to N=70; pilot cohort corrected to 
randomized cohort 
• 
 Removed 'stenosed' in the study objective and design sections 
4.0 
26 Apr 2018 
• 
Increased the number of enrolling sites for the PK cohort to up 
to 3 study centers and indicated PK enrollment first 
• 
Updated study population to include only patients who had 
prior endoscopic sinus surgery (> 30 days with a healed 
mucosa), including ethmoidectomy and uncinectomy 
• 
Edited inclusionary criteria to disallow any additional surgical 
interventions at the baseline balloon dilation procedure 
• 
Edited exclusionary criteria to disallow patients with cystic 
fibrosis 
• 
Included assessment of urinary cortisol over 24 hours at 
baseline (pre-procedure) and 24 hours after the baseline 
procedure (post-procedure) towards additional safety 
assessment in the PK cohort 
• 
Included descriptive statistics for analysis of safety measures 

 
Clinical Study Protocol P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
CONFIDENTIAL 
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May not be reproduced outside of Intersect ENT without written permission from Document Control. 
• 
Updated concomitant medications in the synopsis to match the 
body of the protocol 
• 
Updated flow diagram and schedule of assessments table for 
PK cohort to include urine analysis at baseline and Day 1 post-
procedure; separated screening and baseline visits 
• 
Deleted reference to investigator brochure for site training 
(Section 17.2.1)  
5.0  
21 June 2018 
• 
Added Day 60 follow-up visit to the Randomized cohort and 
updated relevant sections throughout the protocol to include 
Day 60 visit  
• 
Updated Day 30 visit window from ± 3 days to ± 2 days in the 
Randomized cohort 
• 
Modified inclusionary criteria to allow CT scan confirming 
bilateral frontal disease within 30 days prior to randomization 
in the Randomized cohort instead of 30 days prior to 
enrollment 
• 
Updated compatible accessory devices and baseline procedure 
steps to include an optional use of sinus guide catheter handle  
• 
Updated baseline procedure steps to align with the IFU 
• 
Removed IFU as an appendix to the ASCEND protocol 
• 
Updated reference to “guidewire” to “lightwire” throughout 
protocol  
• 
Updated baseline procedure description to allow for dilation of 
the maxillary and/or sphenoid sinus, if clinical necessary in the 
Randomized cohort, with a commercially available balloon 
sinuplasty device prior to randomization 
6.0 
22 October 2018 
• 
Updated the name of the investigational device to UP Drug-
Coated Device and the name of the control device to the ‘UP 
Control Device’  
• 
Changed the timepoint of the primary efficacy endpoint in the 
randomized cohort from Day 30 to Day 14 
• 
Added video-endoscopy grading by an independent reviewer 
at Day 14  
• 
Updated exclusion criteria (a) to exclude patients with ethmoid 
polyposis of grade ≥ 2 
• 
Removed the assessment of estimated FSO diameter post-
dilation following the baseline procedure  
• 
Added a 14-day restriction for use of oral steroids, budesonide 
or other steroid irrigations/rinses or drops, and nebulized 

 
Clinical Study Protocol P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
CONFIDENTIAL 
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steroids administered nasally, prior to the baseline procedure 
in the randomized cohort 
• 
Updated required use of saline sprays/rinses/irrigations starting 
on Day 2 in all subjects in the randomized cohort 
• 
Updated allowance of intranasal corticosteroid sprays after 
Day 14 if medically necessary in the randomized cohort 
• 
Updated Day 60 visit window from ± 3 days to ± 7 days in the 
randomized cohort 
• 
Modified inclusion criteria (f) to allow dilation of the 
maxillary and/or sphenoid sinus with a commercially available 
sinus dilation device, if clinically necessary, prior to 
randomization in the randomized cohort. 
• 
Modified inclusion criteria (k) to include optional use of a 
frontal sinus seeker to assess feasibility of balloon dilation of 
the FSO 
• 
Added a section to describe the personnel and measures to 
achieve blinding in the randomized cohort 
• 
Increased the number of enrolling sites for the randomized 
cohort to up to 12 study centers  
7.0 
12 November 2018 
• 
Changed the timepoint of the primary efficacy endpoint in the 
randomized cohort from Day 14 to Day 30 
• 
Added definition of acute rhinosinusitis to Section 3: 
Definition of terms  
• 
Clarified the use of corticosteroid-eluting implants (including 
PROPEL®, PROPEL® Mini, PROPEL® Contour and 
SINUVA® Sinus Implant) is prohibited 14 days prior to 
baseline 
8.0 
04 April 2019 
• 
Increased the number of enrolling sites for the randomized 
cohort to include up to 15 study centers 
• 
Modified inclusion criterion (k) to confirm access of each FSO 
with a light-assisted or image-guided instrument such as a 
frontal sinus seeker  
• 
Modified exclusion criterion (p) to disallow patients who have 
glaucoma with intraocular pressure > 21 mm Hg even with 
pressure lowering medication  

 
Clinical Study Protocol P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
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TABLE OF CONTENTS 
1 
TITLE PAGE ................................................................................................................................. 1 
2 
LIST OF ABBREVIATIONS ....................................................................................................... 7 
3 
DEFINITIONS OF TERMS ......................................................................................................... 8 
4 
PROTOCOL SUMMARY .......................................................................................................... 12 
5 
STUDY FLOW DIAGRAM ........................................................................................................ 17 
6 
SCHEDULE OF ASSESSMENTS ............................................................................................. 18 
6.1 
PK Cohort ......................................................................................................................... 18 
6.2 
Randomized Cohort .......................................................................................................... 19 
7 
BACKGROUND INFORMATION ........................................................................................... 20 
7.1 
Chronic Rhinosinusitis, Treatment Options and Unmet Clinical Need ............................ 20 
7.2 
Investigational Device ...................................................................................................... 21 
7.3 
Summary of Preclinical Testing ........................................................................................ 22 
7.4 
Summary of Prior Clinical Experience ............................................................................. 23 
8 
STUDY OBJECTIVE .................................................................................................................. 24 
9 
STUDY DESIGN AND ENDPOINTS ........................................................................................ 24 
9.1 
Study Design ..................................................................................................................... 24 
9.2 
Study Endpoints ................................................................................................................ 24 
10 
SUBJECT SELECTION AND WITHDRAWAL ..................................................................... 26 
10.1 
Study Population ............................................................................................................... 26 
10.2 
Eligibility Criteria ............................................................................................................. 26 
10.3 
Subject Withdrawal ........................................................................................................... 27 
11 
SUBJECT TREATMENT AND STUDY PROCEDURES ...................................................... 28 
11.1 
Screening Phase ................................................................................................................ 28 
11.2 
Baseline/Procedure Phase ................................................................................................. 29 
11.3 
Follow-Up Phase ............................................................................................................... 32 
12 
CONCOMITANT MEDICATION ............................................................................................ 33 
13 
MEDICAL AND SURGICAL INTERVENTIONS .................................................................. 34 
13.1 
Medical Intervention ......................................................................................................... 34 
13.2 
Surgical Intervention ......................................................................................................... 35 
14 
ASSESSMENT OF SAFETY ...................................................................................................... 35 
14.1 
Specifications of Safety Parameters .................................................................................. 35 
14.2 
Classification of Adverse Events ...................................................................................... 36 
14.3 
Guidelines for Reporting of Adverse Events .................................................................... 36 
15 
RISK/BENEFIT ASSESSMENT ................................................................................................ 37 
15.1 
Potential Risks .................................................................................................................. 37 
15.2 
Minimization of Potential Risks ....................................................................................... 39 

 
Clinical Study Protocol P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
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15.3 
Potential Risks to Study Subject Confidentiality .............................................................. 39 
15.4 
Potential Benefits from Study Participation ..................................................................... 40 
15.5 
Risk/Benefit Conclusion ................................................................................................... 40 
16 
STATISTICAL CONSIDERATIONS ....................................................................................... 40 
16.1 
Randomization Scheme .................................................................................................... 40 
16.2 
Sample Size Calculation ................................................................................................... 40 
16.3 
Analysis of Primary Endpoints ......................................................................................... 41 
16.4 
Analysis of Secondary Endpoints ..................................................................................... 42 
16.5 
Analysis of Safety Measures ............................................................................................. 42 
16.6 
Handling Steroid or Surgical Interventions ...................................................................... 42 
16.7 
Sensitivity Analysis for the Primary Efficacy Endpoints ................................................. 42 
16.8 
Analysis Populations ......................................................................................................... 43 
17 
STUDY MANAGEMENT ........................................................................................................... 43 
17.1 
Ethical Considerations ...................................................................................................... 43 
17.2 
Sponsor Responsibilities ................................................................................................... 44 
17.3 
Blinding ............................................................................................................................ 46 
17.4 
Investigator Responsibilities ............................................................................................. 47 
17.5 
Protection of Subject Confidentiality ................................................................................ 49 
17.6 
Study Suspension or Early Termination ........................................................................... 49 
17.7 
Site Closeout ..................................................................................................................... 50 
17.8 
Quality Assurance and Supervision by Authorities .......................................................... 50 
17.9 
Final Clinical Study Report .............................................................................................. 51 
17.10 Publication Policy ............................................................................................................. 51 
18 
APPENDIX 1: LIST OF CORTICOSTEROID MEDICATIONS .......................................... 52 
19 
REFERENCES ............................................................................................................................. 53 
 
LIST OF FIGURES 
Figure 1: Schematic of the UP Device ........................................................................................................ 21 
Figure 2: Schematic of the UP Balloon Catheter ........................................................................................ 22 
 
 
 

 
Clinical Study Protocol P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
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2 LIST OF ABBREVIATIONS  
Abbreviations 
Expansion 
ADE 
adverse device effect 
AE 
adverse event 
AERD 
aspirin exacerbated respiratory disease 
ARS 
acute rhinosinusitis 
ASADE 
anticipated serious adverse device effect 
BSD 
balloon sinus dilation 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
COPD 
chronic obstructive pulmonary disease 
CRA 
clinical research associate 
CRF 
case report form 
CRS 
chronic rhinosinusitis 
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 
FSO 
frontal sinus ostium/ostia 
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’ 
IFU 
instructions for use 
INCS 
intranasal corticosteroids 
IRB 
institutional review board 
ITT 
intent-to-treat 
IUD 
intrauterine device 
IV 
intravenous 
LLOQ 
lower limit of quantification 
MF 
mometasone furoate 
PTE 
per-treatment-evaluable 
RESS 
repeat endoscopic sinus surgery 
SAE 
serious adverse event 
SADE 
serious adverse device effect 
SNOT-22 
Sino-Nasal Outcome Test 
UADE 
unanticipated adverse device effect 
USADE 
unanticipated serious adverse device effect 

 
Clinical Study Protocol P500-0118 (The ASCEND Study) 
Doc# CP-00017 Rev. 8.0,  04 April 2019 
 
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3 DEFINITIONS OF TERMS 
Term 
Definition 
Adverse device effect (ADE) 
Adverse event related to the use of an investigational medical device. 
This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device. This 
definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device. [BS EN ISO 14155] 
Adverse event (AE) 
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the 
investigational medical device [BS EN ISO 14155] 
Adhesion/scarring grading scale 
for the ethmoid sinus 
Adhesion/scarring severity in the ethmoid sinus 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 
Adhesion/scarring grading scale 
for the FSO 
Adhesion/scarring in the frontal sinus ostium/ostia (FSO) assessed on a 
4-point scale as follows: 
0:  
No visible granulation/scarring in the FSO 
1:  
Minimal amount of granulation, scarring or contraction            
observed but not obstructing the FSO (intervention not 
warranted) 
2:  
Moderate amount of obstructive granulation, scarring or 
contraction present in the FSO (intervention is warranted) 
3: 
Significant amount of scarring or contraction causing 
obstruction of the FSO requiring intervention (likely to 
compromise patency if not removed) 
Acute rhinosinusitis (ARS) 
Per the 2016 “International Consensus Statement on Allergy and 
Rhinology” definition, patient must have ≤ 4 weeks of symptomatic 
inflammation of the paranasal sinuses and nasal cavity. 
Aspirin exacerbated respiratory 
disease (AERD) 
Aspirin exacerbated respiratory disease, also known as Samter’s Triad, 
is a chronic medical condition that consists of three clinical features: 
asthma, sinus disease with recurrent nasal polyps, and sensitivity to 
aspirin and other non-steroidal anti-inflammatory drugs. 
Case report form (CRF) 
Standardized forms designed to capture study data as required by the 
protocol. 
Chronic rhinosinusitis (CRS) 
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 
Nasal discharge (anterior/posterior) 
o 
Nasal blockage/obstruction/congestion 

 
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Term 
Definition 
o 
Reduction/loss 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 
Device malfunction 
Investigational device: Failure to perform in accordance with its intended 
purpose when used in accordance with the instructions for use or clinical 
investigation plan. [BS EN ISO 14155]  
Compatible accessory devices: Failure 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. [21 CFR 803] 
Enrolled 
Subjects are considered enrolled upon signing the informed consent 
form.  
Estimated FSO diameter 
Smallest and largest diameters of the FSO are estimated endoscopically 
by probing with a 3-mm olive-shaped frontal sinus suction tip and 
reported in mm. 
Inflammation score 
For the purpose of the endoscopic scoring method in this study, the 
term inflammation is a global descriptor defined to include mucosal 
edema, erythema hypertrophy and/or polypoid changes. The 
inflammation present in the frontal recess/FSO is estimated visually 
based on the endoscopic examination on a scale ranging from 0 (no 
visible inflammation) to 100 (severe inflammation) involving extensive 
erythema, edema, or polyposis.  
Intent-to-treat population 
Consists of all subjects in whom a sinus dilation was attempted.  
An attempt occurs when the physician introduces the delivery system 
into the subject’s nostril with the intent of dilation.   
Patency grading scale for the FSO 
Patency of the FSO assessed endoscopically by probing with a 3-mm 
olive-shaped frontal sinus suction tip (“suction tip”) and graded on a 
5-point scale as follows: 
0:  
Occluded (no opening visible) 
1:   Significantly stenosed (not occluded, but unable to pass the 
3-mm suction tip) 
2:   Moderately stenosed (able to easily pass the 3-mm suction tip 
with no additional space around it) 
3:   Minimally stenosed (able to easily pass the 3-mm suction tip 
with additional 1-2 mm space around it) 
4:   Completely patent (able to easily pass the 3-mm suction tip 
with additional > 2 mm space around it) 
Per-treatment-evaluable (PTE) 
population 
Consists of all randomized patients who have received the assigned study 
device in the target sinus, who have no major procedural protocol 
deviations and for whom follow-up data are available. 

 
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Term 
Definition 
Polyp grading scale for the 
ethmoid sinus 
Polyps originating from the ethmoid sinus assessed endoscopically and 
graded on an 8-point scale ranging from 0 to 4 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 completely obstructing the nasal cavity 
Polypoid edema grading scale for 
the FSO 
Polypoid edema in the frontal recess/FSO is assessed on a 4-point scale as 
follows:  
0: 
 Normal mucosa, no visible polyps/mucosal edema  
1: 
 Minimal amount of polyps/mucosal edema 
2:   Moderate amount of polyps/polypoid edema  
3: 
 Expanded amount of polyps/polypoid edema  
Safety population 
Consists of all subjects exposed to investigational device with successful 
dilation of at least one FSO 
Serious adverse event (SAE) 
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 illness or injury; or 
• 
Permanent impairment of a body structure or a body function; 
or 
• 
Inpatient hospitalization or prolongation of existing 
hospitalization; or 
• 
Medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure 
or a body function; or  
• 
Fetal distress, fetal death, 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. [BS EN ISO 14155] 
Serious adverse device effect 
(SADE) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event.  Anticipated serious adverse 

 
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Term 
Definition 
device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk analysis report. 
Sino-Nasal Outcome Test  
(SNOT-22) 
Validated, disease-specific, symptom-scoring instrument consisting of 
22 questions, each scored by patient on a 6-point scale 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 
The maximum total score for all symptoms is equal to 110. 
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 
documents containing source data.  
Subject 
An individual who participates in a clinical investigation.  
Successful dilation of the FSO 
Insertion of the UP Device into the targeted FSO followed by 2 
consecutive complete inflations of the balloon. 
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. [21 CFR 812] 
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. [BS EN ISO 14155; 21 CFR 812] 
Use error 
Act or omission of an act that results in a different medical device 
response than intended by the manufacturer or expected by the user 
NOTE: Use error includes slips, lapses, and mistakes. An unexpected 
physiological response of the subject does not in itself constitute a use 
error. [BS EN ISO 14155] 

 
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4 PROTOCOL SUMMARY 
Study Title 
The ASCEND Study: A Clinical Evaluation of the UP Drug-Coated 
Device in Patients with Chronic Rhinosinusitis  
Objective 
To assess the safety, performance, and efficacy of the UP Drug-Coated 
Device when used in chronic rhinosinusitis (CRS) patients undergoing 
balloon dilation of frontal sinus ostia (FSO) 
Investigational Device 
UP Drug-Coated Device (mometasone furoate, 3000 mcg) and UP 
Control Device (together referred to as “UP Device”) are balloon dilation 
devices intended to dilate the peripheral sinus ostia. 
The UP Drug-Coated Device is intended to dilate and locally deliver 
steroids to the frontal sinus ostia to maintain patency in patients ≥ 18 
years of age. 
Study Design 
Prospective, multicenter, clinical trial enrolling and treating a total of 75 
subjects in two cohorts: 
• 
PK cohort (N=5): A non-randomized cohort to assess the systemic 
safety and performance of the UP Drug-Coated Device for in-office 
bilateral dilation of the FSO (2 inflations in each FSO for a total of 4 
inflations per device). Subsequently, the UP Drug-Coated Device 
may be used to dilate any sphenoid or maxillary sinuses. 
• 
Randomized cohort (N=70): A randomized, intra-patient controlled, 
blinded cohort of 70 subjects to assess the safety and efficacy of the 
UP Drug-Coated Device used for in-office dilation of the FSO. The 
FSO randomized to the treatment (Treatment) will undergo dilation 
using the UP Drug-Coated Device (2 inflations per device) while the 
contralateral FSO (Control) will be dilated with a UP Control Device 
(2 inflations per device). 
Subject Enrollment 
PK cohort: 5 subjects at up to 3 study centers. 
Randomized cohort: 70 subjects at up to 15 study centers across the U.S.  
 The PK cohort will enroll first. 
Study Population 
Patients ≥ 18 years of age with chronic rhinosinusitis (CRS) who had 
prior endoscopic sinus surgery (ESS) including ethmoidectomy and 
uncinectomy and are candidates for balloon dilation because they present 
with bilateral stenosis of the frontal recess/FSO due to scarring or 
polypoid edema, confirmed on endoscopy.  
Eligibility Criteria 
Key inclusion criteria: 
• 
Confirmed diagnosis of CRS 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: 
 
nasal discharge (anterior/posterior) 
 
nasal blockage/obstruction/congestion 

 
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 
reduction/loss 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 (CT) 
 
Evidence of purulence coming from paranasal sinuses or 
ostiomeatal complex  
• 
Bilateral disease in the frontal sinuses (Lund-Mackay score ≥ 1 on 
each side) on CT scan within 30 days prior to enrollment in the PK 
cohort and prior to randomization in the randomized cohort. 
• 
Patient has bilateral obstruction of the frontal recess/FSO due to 
scarring and/or polypoid edema confirmed on endoscopy (patency 
grade of 0 or 1 for each FSO). 
• 
Balloon dilation of the FSO judged to be feasible (use light-assisted 
or image-guided instrument such as a frontal sinus seeker tip to 
confirm access of each FSO) and medically appropriate. 
• 
Patient has had prior ESS (> 30 days with a healed mucosa) 
including bilateral ethmoidectomy (anterior or total) and 
uncinectomy for better visualization of the FSO. Note: No additional 
surgical interventions will be allowed at baseline/procedure. Dilation 
of the maxillary and/or sphenoid sinus can be performed with a 
commercially available sinus dilation device, if clinically necessary, 
prior to randomization in the randomized cohort. 
Key exclusion criteria: 
• 
Expanded amount of ethmoid polyposis (grade > 2 PK cohort, grade 
≥ 2 randomized cohort)  
• 
Complications from prior ESS or balloon dilation procedure (e.g., 
cerebrospinal fluid leak or injury to the skull base) 
• 
History of aspirin exacerbated respiratory disease (AERD) 
• 
Patient is a current smoker 
• 
History of allergy or intolerance to mometasone furoate 
• 
Oral-steroid dependent condition 
• 
Evidence of acute rhinosinusitis, invasive fungal sinusitis or another 
disease or condition expected to compromise survival or ability to 
complete assessments during the 30-day follow-up period in the PK 
cohort and during the 60-day follow-up period in the randomized 
cohort 
• 
Use of parenteral and injected steroids (e.g., Kenalog) 30 days prior 
to the baseline procedure  
• 
Use of oral steroids, budesonide or other sinus steroid 
irrigations/rinses or drops, nebulized steroids administered nasally 
14 days prior to screening in the PK cohort and prior to baseline in 
the randomized cohort 
Primary Endpoints 
PK cohort: Successful dilation of attempted FSO using the UP Drug-
Coated Device with no unanticipated serious adverse device effects 
(USADE)  

 
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Randomized cohort: Difference in the patency grade of the FSO between 
treatment sides at Day 30, as determined by an independent, blinded 
sinus surgeon based on the centralized video-endoscopy review 
Secondary Endpoints 
Endoscopic endpoints in the FSO by clinical investigators at specified 
timepoints through Day 30 in the PK cohort and through Day 60 in the 
randomized cohort: 
• 
Estimated diameter, smallest and largest (mm) 
• 
Frequency and grade of patency (5-point categorical scale) 
• 
Inflammation (0-100 scale) 
• 
Frequency and severity of adhesion/scarring (4-point categorical 
scale) 
• 
Frequency and grade of polypoid edema (4-point categorical scale) 
• 
Need for and frequency of post-dilation interventions (e.g., medical, 
repeat dilation, surgical) 
Endoscopic endpoints in the FSO by independent reviewer in the 
randomized cohort: 
• 
Estimated diameter, smallest and largest (mm) at Day 14 and Day 30 
• 
Frequency and grade of patency at Day 14 and frequency of patency 
at Day 30 (5-point categorical scale) 
• 
Inflammation (0-100 scale) at Day 14 and Day 30 
• 
Frequency and severity of adhesion/scarring (4-point categorical 
scale) at Day 14 and Day 30 
• 
Frequency and grade of polypoid edema (4-point categorical scale) 
at Day 14 and Day 30 
• 
Need for and frequency of post-dilation interventions (e.g., medical, 
repeat dilation, surgical) at Day 14 and Day 30 
 
Patient-reported outcomes (PK cohort only):           
• 
Change from baseline to Day 14 and Day 30 in Sino-Nasal Outcome 
Test (SNOT-22) scores 
Safety Evaluation  
PK cohort:  
• 
Measurement of plasma concentrations of MF and cortisol at 
baseline before the baseline procedure (dilation) and at 0.5, 1, 2, 4, 
and 24 hours after dilation, and again in the morning of Days 3, 7, 
14 and 30 
o 
A validated bioanalytical method for human plasma MF with a 
lower limit of quantification (LLOQ) of 0.25 pg/mL 
o 
A validated bioanalytical method for cortisol with a LLOQ of 
1.00 ng/mL 
• 
Measurement of urinary cortisol excretion for 24 hours prior to the 
baseline procedure and for 24 hours after the baseline procedure 
o 
A validated bioanalytical method for human urinary cortisol 
with a LLOQ of 1.00 ng/mL 

 
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All adverse events reported by subjects between enrollment and Day 30 
(end of study) will be tabulated. 
Randomized cohort: All adverse events reported by subjects between 
enrollment and Day 60 (end of study) will be tabulated. 
Concomitant 
Medications 
• 
Leading up to the baseline procedure, there is a 30-day restriction for 
use of parenteral and injected steroids (e.g., Kenalog). 
• 
Leading up to the baseline procedure, a 14-day restriction for use of 
oral steroids, budesonide or other sinus steroid irrigations/rinses 
or drops, nebulized steroids administered nasally. 
• 
After the baseline procedure, subjects will be allowed in the PK 
cohort and required in the randomized cohort to use saline 
sprays/rinses/irrigations starting from Day 2. 
• 
If infection is suspected at any time during the study, treatment with 
antibiotics will be permitted. 
• 
Use of intranasal corticosteroid (INCS) sprays will be allowed 
starting after Day 14 visit in the randomized cohort, if medically 
necessary, and not allowed throughout the 30-day follow-up 
duration in the PK cohort. 
• 
Use of other corticosteroids (e.g., oral, parenteral, injections, 
budesonide or other sinus steroid irrigations/rinses or drops, breath 
powered steroid delivery [e.g. XHANCE™, fluticasone 
proprionate], nebulized steroids administered nasally) will not be 
permitted during the study follow-up unless clinically necessary.  
• 
Use of orally-inhaled steroids for control of asthma will be 
permitted, if already on such medications. 
• 
Use of corticosteroid-eluting sinus implants (PROPEL®, 
PROPEL® Mini, PROPEL® Contour, SINUVA® Sinus Implant) or 
other nasal packing and spacers is prohibited 14 days prior to 
baseline and during the baseline procedure and through Day 30 in 
the PK cohort and through Day 60 in the randomized cohort. 
• 
To the extent possible, subjects will be maintained on stable 
regimens of leukotriene inhibitors and/or immunotherapy for 
allergies, if currently on such regimens.  
Follow-up 
PK cohort: Each subject will return for 6 follow-up visits at Days 1 
(24 hr collection), 3, 7, 14, 21 and 30. All blood draws during follow-up 
should occur in the morning. 
Randomized cohort: Each subject will return for 5 follow-up visits at 
Days 7, 14, 21, 30 and 60. 
Subjects in both cohorts 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, and/or 
sinus-related adverse events requiring medical evaluation.  

 
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Duration of Study Period  For a given subject in the PK cohort: Approximately 32 days = screening 
visit (1 day) + baseline/procedure (1 day) + follow-up (30 days)  
For a given subject in the randomized cohort: Approximately 62 days = 
screening visit (1 day) + baseline/procedure (1 day) + follow-up (60 
days)  
Overall: Approximately 8 months = 6-month enrollment phase + 2- 
month follow-up. 

 
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5 STUDY FLOW DIAGRAM 
 
Day 7 (± 2 d)
 Enrollment/Screening
Medications
Study Population
CRS patients (≥ 18 yr) with bilateral 
frontal sinus disease confirmed on CT (LM 
score ≥ 1 on each side) and bilateral 
stenosis of frontal sinus ostia confirmed 
on endoscopy 
Abbreviations: 
CT, computed tomography; FSO, frontal sinus ostia; LM, Lund-Mackay score; SNOT-22, Sino-nasal Outcome Test 
Saline rinses necessary 
starting Day 2
Intranasal corticosteroid 
sprays starting after Day 14 
visit, if clinically necessary 
Corticosteroids (e.g oral, 
parenteral, injection, 
budesonide or other steroid 
irrigations/rinses/drops, 
breath powered steroid 
inhalers, steroid nebulizers 
administered nasally) not 
allowed unless clinically 
necessary 
Corticosteroid-eluting 
implants or other nasal 
packing and spacers 
prohibited
Antibiotics allowed if 
clinically necessary 
Day 7 (± 2 d) 
Endoscopic grading
ENT
Endoscopic grading
(before balloon dilation)
Endoscopic grading
Day 14 (± 2 d)
Endoscopic grading and 
video-endoscopy review
Day 21 (± 2 d)
Endoscopic grading
Day 30 (± 2 d)
Endoscopic grading and 
video-endoscopy review
Randomize
 (Intra-patient 
control)
Treatment  Side 
(balloon dilation 
with Drug-Coated 
Device)
Control Side
(balloon dilation 
with Control 
Device)
Randomized Cohort
N=70 subjects
Day 14 (± 2 d)
Day 30 (± 3 d)
Day 1 
Bilateral balloon
 dilation with Drug-
Coated Device
PK Cohort
N=5 subjects
Prior to the baseline 
procedure:
No parental or injected 
steroids for ≥ 30 days
 
No oral steroids, 
budesonide or other steroid 
irrigations/rinses/drops, 
nebulized steroids, 
corticosteroid-eluting 
implants for ≥ 14 days
Day 21 (± 2 d)
Patient  
SNOT-22
(before balloon 
dilation)
SNOT-22
Blood draw
24 hr
PK assessment 
Blood draw 
Baseline (pre-procedure),
0.5 hr, 1 hr, 2 hr, 4 hr 
(after-procedure)
Blood draw
Blood draw
Blood draw
SNOT-22
PK Cohort
Medications
Saline rinses allowed 
starting Day 2
Intranasal corticosteroid 
sprays not allowed 
Corticosteroids (e.g oral, 
parenteral, injection, 
budesonide respules, 
rinses or drops, breath 
powered steroid inhalers, 
steroid nebulizers 
administered nasally) not 
allowed unless clinically 
necessary
Repeat balloon dilation or 
ESS allowed if clinically 
necessary
Antibiotics allowed if 
clinically necessary 
Prior to the baseline 
procedure:
No parental or injected 
steroids for ≥ 30 days
No oral steroids, 
budesonide or other 
steroid irrigations/rinses/
sprays or drops, nebulized 
steroids for ≥ 14 days
Randomized Cohort
Endoscopic grading
ENT
Endoscopic grading 
(before balloon dilation)
* FSO diameter assessment 
before/after balloon 
dilation
Endoscopic grading 
Endoscopic grading
Endoscopic grading
Endoscopic grading
Blood draw
Endoscopic grading
Day 60 (± 7 d)
Day 3 

 
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6 SCHEDULE OF ASSESSMENTS  
6.1 
PK Cohort 
Assessment 
Screening 
Baseline/ 
Procedure 
Day 1 
 
Day 3 
 
Day 7 
(±2 d) 
Day 14 
(±2 d) 
Day 21 
(±2 d) 
Day 30 
(±3 d) 
Informed consent 
X 
 
 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
 
 
CT scan (≤ 30 days prior to enrollment) 
X 
 
 
 
 
 
 
 
Blood sample collection (~11 ml) 
 
Xa 
Xb 
Xb 
Xb 
Xb 
 
Xb 
24-hour urine collection 
 
Xc 
Xc 
 
 
 
 
 
In-office bilateral FSO dilation 
 
X 
 
 
 
 
 
 
Endoscopic grading and recording 
X 
Xd 
 
 
X 
X 
X 
X 
Sino-Nasal Outcome Test (SNOT-22)  
 
Xd 
 
 
 
X 
 
X 
Concomitant medications  
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event reporting 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test (female subjects of 
childbearing potential) 
Xe,f 
Xe,f 
 
 
 
 
 
 
Documented birth control (female subjects) 
 
 
X 
X 
X 
X 
X 
X 
Abbreviations: CT, computed tomography; d, days; FSO, frontal sinus ostium/ostia; min, minutes; ml, milliliter. 
a. Blood draws to occur at baseline, before balloon dilation procedure and again at Hour 0.5 (±5 min), 1 (±5 min), 
2 (±10 min), and 4 (±15 min) after the end of baseline procedure 
b. All blood draws should occur in the morning and at approximately the same time of the day during the follow-up 
visits. Day 1 blood draw to occur 24 hours (±3 hours) after the baseline procedure. Day 3 blood draw to occur 72 
hours (±3 hours) after the baseline procedure 
c. Urine samples will be collected for a 24-hour duration prior to the baseline visit (pre-procedure) and for a 24-hour 
duration following the baseline procedure (post-procedure) 
d. All endoscopic assessments and SNOT-22 performed prior to the baseline procedure, except for the FSO 
diameter, which must be performed before and after the balloon dilation procedure.   
e. Female subjects with reproductive potential are required to undergo a urine pregnancy test at screening and prior 
to the baseline procedure. 
f. Female subjects are required to confirm their nursing status at screening and baseline  

 
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6.2 
Randomized Cohort 
Assessment 
Screening 
Baseline/ 
Procedure 
Day 7  
(±2 d) 
Day 14  
(±2 d) 
Day 21 
(±2 d) 
Day 30 
(±2 d) 
Day 60 
(±7 d) 
Informed consent 
X 
 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
 
CT scan (≤ 30 days prior to randomization) 
 
X 
 
 
 
 
 
In-office bilateral FSO dilation 
 
X 
 
 
 
 
 
Endoscopic grading and recording 
X 
Xa 
X 
X 
X 
X 
X 
Video-endoscopy grading (independent 
reviewer) 
 
 
 
X 
 
X 
 
Concomitant medications  
X 
X 
X 
X 
X 
X 
X 
Adverse events reporting 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test (female subjects of 
childbearing potential) 
Xb,c 
Xb,c 
 
 
 
 
 
Documented birth control (female subjects) 
 
 
X 
X 
X 
X 
X 
Abbreviations: CT, computed tomography; d, day; FSO, frontal sinus ostium/ostia. 
a All endoscopic assessments performed prior to baseline procedure. 
b  Female subjects with reproductive potential are required to undergo a urine pregnancy test at screening and prior to 
the baseline procedure. 
c Female subjects are required to confirm their nursing status at screening and baseline. 
 

 
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7 BACKGROUND INFORMATION 
7.1 
Chronic Rhinosinusitis, Treatment Options and Unmet Clinical Need 
Chronic rhinosinusitis (CRS) is defind as sinonasal inflammation persisting for more than 
12 weeks. Sinusitis is one of the most prevalent chronic diseases, affecting about 12% of the 
adult population (Blackwell 2014). It causes a significant burden to the society at large (Rudmik 
2014), as well as to the patient in terms of economics (Bhattacharyya 2011; Caulley 2015) and 
quality of life (Soler 2011). The cardinal symptoms of CRS include nasal congestion, nasal 
drainage (mucopurulence draining anteriorly or posteriorly), facial pain or pressure, and decrease 
or loss of sense of smell (Orlandi 2016). Addressing the underlying causes of CRS and 
controlling the symptoms caused by the inflammatory process have been the focus of medical 
therapy. Medical management of CRS includes intranasal corticosteroids, supplemented with a 
combination of antihistamines, antibiotics and/or oral steroids (Orlandi 2016). Patients who fail 
to respond to medical therapy may be referred for endoscopic sinus surgery (ESS) to improve 
ventilation and mucociliary clearance through the natural ostia (Fokkens 2012).  
ESS has been demonstrated to improve patient-reported symptoms and quality of life in select 
patients with CRS who have persistent symptoms despite appropriate medical therapy. Longer-
term success rates for primary ESS are as high as 98% (Ramadan 1999; Senior 1998). However, 
the surgical outcomes are compromised by incomplete surgery, postoperative inflammation and 
adhesions, and recurrence of polyposis, which often require meticulous postoperative 
debridement and effective medical management (Bhattacharyya 2004; Senior 1998). While ESS 
with traditional instrumentation has been effective at enlarging the ostia, balloon dilation is 
increasingly used as either a stand-alone procedure or as part of a hybrid surgery with traditional 
methods (Chaaban 2017; Svider 2017). This is particularly true when treating the frontal sinus 
where stenosis of the neo-ostium is a common sequela.  
Fueled by the need for minimally invasive, mucosa-sparing techniques, a catheter-based 
approach was introduced to reduce mucosal trauma, prevent scarring, bleeding and associated 
sequelae. Balloon sinus dilation (BSD) is a minimally invasive sinus surgery procedure to 
mechanically dilate the obstructed sinus ostia by inflating the balloon in the target sinus ostia.  
BSD displaces and compresses mucosa and causes microfracture of the underlying 
circumferential bone, enlarging the sinus ostia and improving drainage. Patients treated with 
BSD have been shown to have faster recovery, have less postoperative pain, and require fewer 
debridements than those undergoing traditional ESS (Catalano and Payne 2009; Chandra 2016; 
Levine 2008). 
The safety and effectiveness of BSD in the paranasal sinuses have been evaluated in several 
clinical studies in treatment of stenosed peripheral sinuses in CRS patients (Achar 2012; Bikhazi 
2014; Bolger 2007; Cutler 2013; Friedman 2008; Koskinen 2017; Kuhn 2008; Levine 2008; 
Plaza 2011; Weiss 2008). While the device is low risk with no major intraoperative 
complications (Koskinen 2017; Levine 2008), a known response to the dilation itself is periosteal 
mucosal edema and ostial narrowing post-dilation (Bolger 2007).  
Intersect ENT has developed the UP Drug-Coated Device which is a drug coated sinus dilation 
device intended to dilate and locally deliver drug to the treated sinus ostia in CRS patients.  The 

 
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device is coated with 3000 mcg of the corticosteroid (MF), to help minimize 
edema/inflammation following the sinus dilation procedure.  
7.2 
Investigational Device  
Intended use 
The UP Drug-Coated Device is intended to dilate and locally deliver steroids to the frontal sinus 
ostia to maintain patency in patients ≥ 18 years of age. 
Device description 
The UP Drug-Coated Device and the UP Control Device (hereafter referred to as “UP Device”) 
are over-the-wire sinus balloon catheters with a balloon at the distal end (with or without MF-
coating). Figure 1 depicts a schematic representation of the UP Device. On the proximal end of 
the device, there are two primary ports: the first port is compatible with an inflation device that is 
used to inflate the balloon with saline for sinus dilation; and the second port is intended to be 
used with a compatible lightwire and guide catheter to confirm access into the target sinus. The 
usable working length is 207 mm.  
 
 
Figure 1: Schematic of the UP Device 
Balloon catheter 
The UP balloon catheter is shown in Figure 2 and comprises a nylon balloon and distal shaft 
with markers to denote balloon distance from the guide catheter. The shaft markers on the distal 
end of the catheter aid in proper placement. The yellow marker denotes the proximal end of the 
balloon and the white markers are spaced 1 cm (single band) and 2 cm (double band) away from 
the proximal end of the balloon. The UP Device has a soft atraumatic distal tip. The balloon 
diameter is 6 mm in diameter and the 20 mm of working length when inflated to a pressure of 12 
atmospheres (atm). 

 
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Figure 2: Schematic of the UP Balloon Catheter 
Balloon coating 
UP Drug-Coated Device: The coating on the balloon of the UP Drug-Coated Device contains 
3000 mcg of mometasone furoate (the active ingredient) in a polymer matrix of polyethylene 
glycol and polysorbate (inactive ingredients). The coating on the balloon is hydrophilic and 
designed to provide immediate release of MF during dilation into the apposing sinus mucosa.  
The device locally delivers drug to the treated sinus ostia to reduce edema/inflammation 
following sinus dilation.   
UP Control Device: Similar to the UP Drug-Coated Device, the UP Control Device is an over-
the-wire sinus balloon catheter. The UP Control Device does not contain drug and is identical to 
the UP Drug-Coated Device with respect to dimensions of the balloon.  
No changes in the investigational device are anticipated during the study. Any changes in the 
investigational device during the conduct of the study will be documented and maintained by 
Intersect ENT.  
Compatible accessory devices  
The UP Device is intended to be used with 0.035” compatible lightwire (e.g., Relieva Luma® 
Sentry Sinus Illumination System), 70° sinus guide catheters (e.g. Relieva Flex™ Sinus Guide 
Catheter Tip, F-70 C), compatible inflation device (e.g., Acclarent® SE Inflation Device) and 
the sinus guide catheter handle (e.g., Relieva Sidekick Sinus Guide Catheter Handle (Low 
Profile) [Sidekick LP]).  
7.3 
Summary of Preclinical Testing  
Preclinical testing conducted on the investigational device included bench studies (mechanical 
and analytical), simulated use testing in a sinus model, shelf-life studies, biocompatibility, 
packaging and sterilization studies. These studies demonstrated that the investigational device 
meets its specifications and the safety and performance requirements for use in humans. 

 
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Additionally, Intersect ENT conducted a series of preclinical studies using the sheep model to 
ascertain preliminary safety and feasibility of delivering MF to the sinus ostia. Plasma MF 
concentrations were maximum at 1-hour post-dilation. The localized release of MF from the UP 
Drug-Coated Device inflated once in both left and right FSO resulted in transient low systemic 
exposure to the drug. Systemic MF exposure peaked at 104 pg/mL (Cmax) by 1 hour (Tmax) but 
declined rapidly over 72 hours to negligible or below LLOQ of 20 pg/mL based on assays 
validated for sheep plasma.  
Sinus tissue MF exposure in animal studies demonstrated that tissue healing was not impaired by 
the UP Drug-Coated Device. Based on visual assessment, no gross adverse tissue responses of 
edema or erythema and no clinical signs of infection were observed at any time point through 
30 days following dilation.  
7.4 
Summary of Prior Clinical Experience 
The ASCEND study is the first human study with the investigational device.  
The safety and efficacy of delivering MF locally to the sinus ostia via bioabsorbable implants 
have been extensively studied in several randomized controlled trials. The PROPEL® Family of 
Sinus Implants was studied in 6 clinical trials in the U.S., totaling over 350 patients. All 6 studies 
were designated as non-significant risk (NSR) studies. The PROPEL Family of Sinus Implants is 
coated with the same corticosteroid, MF, and have demonstrated adequate safety. The PROPEL 
sinus implant is intended for use in patients ≥ 18 years of age following ethmoid sinus surgery to 
maintain patency, thereby reducing the need for post-operative intervention such as surgical 
adhesion lysis and/or use of oral steroids. The PROPEL sinus implant separates mucosal tissues, 
provides stabilization of the middle turbinate, prevents obstruction by adhesions, and reduces 
edema. Since commercialization of the PROPEL sinus implant in 2011, the PROPEL Family of 
Sinus Implants have been used in treatment of over 200,000 patients. 
In order to support the safety of the UP Drug-Coated Device with 3000 mcg of MF, a 
pharmacokinetic (PK) simulation was performed using published human plasma MF PK 
concentrations, following an intravenous (IV) administration of 400 mcg of MF and a simulated 
absorption process from the sinus following nasal administration of MF. Available human PK 
data for the approved MF products (specifically a dry-powder inhalation [DPI] administration of 
Asmanex®) and supportive data from MF plasma concentration-time profiles generated with the 
UP Drug-Coated Device were used for comparison. Predicted AUC values with MF from the UP 
Drug-Coated Device (459-1376 pg.hr/ml) were similar to those reported for the approved daily 
doses of up to 880 mcg of MF administered as DPI and metered dose inhalation (MDI) (93-1383 
pg.hr/ml). Predicted Cmax ranges for the UP Drug-Coated Device (105-315 pg/ml) overlapped 
with the Cmax ranges reported for approved doses of DPI and MDI (35.2-189 pg/ml) but were 
higher for those simulations which assumed a higher fraction of dose delivered (90%) or at 
higher (2%) bioavailability than observed for approved products. The predicted MF exposures 
(AUC and Cmax) from the 3000 mcg UP Drug-Coated Device are comparable to observed MF 
exposures described in publicly available documentation at doses up to 1600 mcg/day (Data on 
file at Intersect ENT). 

 
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8 STUDY OBJECTIVE 
To assess the safety, performance, and efficacy of the UP Drug-Coated Device when used in 
CRS patients undergoing balloon dilation of FSO. 
9 STUDY DESIGN AND ENDPOINTS 
9.1 
Study Design 
This is a prospective, multicenter clinical trial designed to evaluate the safety, performance, and 
efficacy of the UP Drug-Coated Device in CRS patients who are candidates for in-office balloon 
dilation of the frontal recess/FSO.  
The trial consists of 2 cohorts: 
PK cohort: A non-randomized cohort of 5 subjects who are scheduled to undergo bilateral 
balloon dilation of the FSO. The UP Drug-Coated Device will be used to perform balloon 
dilation in the FSO (2 inflations in each FSO for a total of 4 inflations per device). 
Randomized cohort: A randomized, intra-patient controlled, blinded cohort of 70 subjects who 
are scheduled to undergo bilateral balloon dilation of the FSO. Subjects will be randomized to 
undergo balloon dilation with the UP Drug-Coated Device (2 inflations per device) in one FSO 
(Treatment) while the contralateral side will undergo balloon dilation with the UP Control 
Device (Control).  
The PK cohort will enroll first. Subjects in the PK cohort will be followed for 30 days (± 3 d) 
post-procedure and subjects in the randomized cohort will be followed for 60 days (± 7 d) post-
procedure.  
9.2 
Study Endpoints 
9.2.1 
Primary Endpoints  
PK cohort: Successful balloon dilation of attempted FSO using the UP Drug-Coated Device with 
no unanticipated serious adverse device effects (USADE). Successful dilation is defined as 
insertion of the UP Drug-Coated Device into the targeted FSO followed by 2 consecutive 
complete inflations of the balloon.  
Randomized cohort: Difference in patency grade of the FSO between treatment sides at Day 30 
as determined by an independent, blinded sinus surgeon based on the centralized, video-
endoscopy review. 
• Patency of the FSO is assessed endoscopically by probing with a 3-mm olive-shaped 
frontal sinus suction tip (“suction tip”) and graded on a 5-point scale. 

 
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9.2.2 
Secondary Endpoints 
Endoscopic measures in the FSO by clinical investigators at specified timepoints through Day 30 
in the PK cohort and through Day 60 in the randomized cohort: 
• Estimated FSO diameter, smallest and largest (mm) 
• Frequency and grade of patency (5-point categorical scale) 
• Inflammation (0-100 scale) 
• Frequency and severity of adhesion/scarring (4-point categorical scale) 
• Frequency and grade of polypoid edema (4-point categorical scale) 
Need for and frequency of post-dilation interventions (e.g., medical, repeat dilation, 
surgical) 
Endoscopic endpoints in the FSO by independent reviewer in the randomized cohort: 
• Estimated diameter, smallest and largest (mm) at Day 14 and Day 30 
• Frequency and grade of patency at Day 14 and frequency of patency at Day 30 (5-point 
categorical scale) 
• Inflammation (0-100 scale) at Day 14 and Day 30 
• Frequency and severity of adhesion/scarring (4-point categorical scale) at Day 14 and Day 
30 
• Frequency and grade of polypoid edema (4-point categorical scale) at Day 14 and Day 30 
• 
Need for and frequency of post-dilation interventions (e.g., medical, repeat dilation, surgical) 
at Day 14 and Day 30 
Patient-reported outcomes (PK cohort only): 
• Change from baseline to Day 14 and Day 30 in Sino-Nasal Outcome Test (SNOT-22) 
scores 
See Section 3 Definitions of Terms. 
9.2.3 
Safety Evaluation  
In the PK cohort, systemic safety will be evaluated via measurements of plasma MF and cortisol 
concentrations and 24-hour urinary cortisol excretion. Morning plasma MF and cortisol 
concentrations before the baseline procedure (dilation) and at 0.5, 1, 2, 4, and 24 hours after 
dilation, and again in the morning of Day 3, 7, 14 and 30 will be analyzed. The MF 
concentrations will be determined using a validated bioanalytical method a lower limit of 
quantification (LLOQ) of 0.25 pg/mL. Plasma cortisol will be determined using a validated 
bioanalytical method with a LLOQ of 1.00 ng/mL.  Measurement of urinary cortisol excretion for 
24 hours prior to the baseline procedure and for 24 hours after the baseline procedure will be 
analyzed using a validated bioanalytical method with a LLOQ of 1.00 ng/mL. 
In both cohorts, all adverse events (AE) reported by subjects between enrollment (i.e., consent 
date) and the Day 30 follow-up visit in the PK cohort and the Day 60 follow-up visit in the 
randomized cohort (end of study) will be tabulated. Each AE will be evaluated by clinical 
investigators in terms of seriousness, severity (i.e., mild, moderate, severe) and strength of 

 
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relationship (i.e., not related, unlikely related, probably related, definitely related) to study drug, 
study investigational device, study accessory device, and dilation procedure. 
Device malfunctions and use errors will be reportable as applicable for both the investigational 
and the accessory devices.    
10 SUBJECT SELECTION AND WITHDRAWAL 
10.1 
Study Population 
The study population will consist of patients ≥ 18 years of age with CRS who had prior ESS, 
including ethmoidectomy and uncinectomy, and are candidates for balloon dilation because they 
present with bilateral stenosis of the frontal recess/FSO due to scarring or polypoid edema, 
confirmed on endoscopy. 
10.2 
Eligibility Criteria 
Subjects are eligible for treatment (PK and randomized cohort) after they 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 CRS, as defined in the 2016 “International Consensus 
Statement on Allergy and Rhinology”.  
e. Patient has bilateral disease in the frontal sinuses (Lund-Mackay score ≥ 1 on each side) on 
CT scan within 30 days prior to enrollment in the PK cohort and prior to randomization in 
the randomized cohort. 
f. Patient has had prior ESS (> 30 days with a healed mucosa), including bilateral 
ethmoidectomy (anterior or total) and uncinectomy for better visualization of the FSO. Note: 
No additional surgical interventions will be allowed at baseline/procedure. Dilation of the 
maxillary and/or sphenoid sinus can be performed with a commercially available sinus 
dilation device, if clinically necessary, prior to randomization in the randomized cohort. 
g. Patient is able to tolerate topical/local anesthesia. 
h. Female patients of reproductive potential must not be pregnant or nursing and must agree to 
not become pregnant during their participation in the study. 
i. Female patients of childbearing potential must agree to use consistent and acceptable 
method(s) of birth control during their participation in the study. 
j. Patient has bilateral obstruction of the frontal recess/FSO due to scarring and/or polypoid 
edema confirmed on endoscopy (patency grade of 0 or 1 for each FSO). 

 
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k. Balloon dilation of the FSO with a 6 mm balloon is judged to be feasible (use light-assisted 
or image-guided instrument such as a frontal sinus seeker tip to confirm access of each FSO  
) and medically appropriate. 
Exclusion criteria 
a. Patient has expanded amount of ethmoid polyposis (grade > 2 in the PK cohort, and grade ≥ 
2 in the randomized cohort). 
b. Complications from prior ESS or balloon dilation procedure (e.g., cerebrospinal fluid leak or 
injury to the skull base).  
c. History of aspirin exacerbated respiratory disease (AERD). 
d. Patient is a current smoker. 
e. Patient has known history of allergy or intolerance to MF. 
f. Patient has used parenteral or injected steroids (e.g., Kenalog) during 30 days prior to the 
baseline procedure.  
g. Patient has clinical evidence of acute rhinosinusitis, as defined in the 2016 “International 
Consensus Statement on Allergy and Rhinology”.  
h. Patient has oral-steroid dependent condition such as chronic obstructive pulmonary disease 
(COPD) or asthma. 
i. Patient has used oral steroids, budesonide or other sinus steroid irrigations/rinses or drops, 
nebulized steroids administered nasally during 14 days prior to the screening in the PK 
cohort and prior to baseline procedure in the randomized cohort 
j. Patient has clinical evidence or suspicion of invasive fungal sinusitis (e.g., bone erosion on 
prior CT scan, necrotic sinus tissue). 
k. Patient has known history of human immunodeficiency virus (HIV), immunoglobulin G or A 
subclass deficiency or cystic fibrosis. 
l. Patient has evidence of severe concomitant disease or condition expected to compromise 
survival or ability to complete assessments during the 30-day study follow-up period in the 
PK cohort and during the 60-day study follow-up period in the randomized cohort 
(e.g., cancer). 
m. Patient is currently participating in another clinical study.  
n. Patient has known dehiscence of the lamina papyracea. 
o. Patient has evidence of active tuberculosis or active viral illness (e.g., ocular herpes simplex, 
chickenpox, and measles). 
p. Patient has glaucoma (prior ocular exam with intraocular pressure of > 21 mm Hg and 
pressure lowering medication given) or posterior subcapsular cataract. 
10.3 
Subject Withdrawal 
Study subject may be withdrawn or terminated for the following reasons: 
• Subject death 

 
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• Concomitant disease or any pre-existing disease or condition that precludes subject’s 
participation.  
• Subject voluntarily chooses not to participate further in the study.  
• Subject’s non-compliance with study procedures. 
• Lost to follow-up: the subject has missed 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 clinical investigator’s opinion, a significant safety concern arises that requires subject 
discontinuation. 
• In the clinical investigator’s opinion, it is not in the best interest of the subject to continue 
study participation. 
• In the sponsor’s or IRB’s opinion, it is not in the best interest of subject to continue the study. 
If a subject decides to withdraw from the study, clinical investigator should follow patients with 
ongoing AEs till resolution according to the standard of care. 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, clinical 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).  
Consent, enrollment, and screening 
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.  
Clinical investigators or designees will approach the patient to obtain written informed consent. 
The background of the proposed study, the dilation procedure, the follow-up schedule and all 
potential risks and benefits will be carefully explained to each patient. The clinical investigator 
or designee obtaining the informed consent shall: 

 
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• 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 
Institutional Review Board (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 the Electronic Data Capture (EDC) system and entered into the study database. Upon 
enrollment, subjects will have a screening assessment. 
The screening assessment for both cohorts will include: 
• CT scan (must be performed within 30 days prior to enrollment in the PK cohort and 
prior to randomization in the randomized cohort),  
• Endoscopic examination, grading and video recording, 
• Female subjects of reproductive potential must confirm their nursing status, undergo a 
urine pregnancy test, and be informed about acceptable birth control methods as part of 
the screening assessment and again at baseline.  
PK cohort subjects who pass the screening assessment will be asked to collect urine samples for 
a 24-hour duration prior to the baseline visit.  
For the randomized cohort subjects, if the screening visit occurs on the same day as the 
baseline/procedure visit, all assessments will be recorded in the baseline visit forms. See Section 
5 Study Flow Diagram and Section 6 Schedule of Assessments. All subjects who do not pass 
the screening assessment, including inability to confirm access to each FSO, will be considered 
as screen failures and will be terminated from the study. The reason for ineligibility will be 
recorded in the EDC system.  
11.2 
Baseline/Procedure Phase 
Baseline assessment 
Upon meeting eligibility requirements, subjects in both cohorts will undergo a baseline 
endoscopic examination, including 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: 
Established use of oral, injection or implantable hormonal contraceptives;  
• Double-barrier methods (i.e., intra-uterine devices) and barrier contraceptives (i.e., 
condom, diaphragm or cervical/vault caps) used with spermicide (foam, gel, film, cream 
or suppository);  

 
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• Female sterilization (e.g., tubal occlusion, hysterectomy or bilateral salpingectomy); or 
• Vasectomized male partner, if the sole partner for the subject. 
Note: The baseline endoscopic assessment and pregnancy testing must be performed before the 
dilation procedure. 
PK cohort: Baseline assessment will also include:  
• SNOT-22 questionnaire.  
• A blood sample collection prior to the baseline procedure. 
• Instructions for urine sample collection through 24 hours after the baseline procedure 
o Urine collection starting with the void after the procedure through 24 hours on 
following day. 
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 
All UP Devices will be provided by the study sponsor and must be used according to the 
instructions for use (IFU). Subjects will undergo bilateral in-office dilation of the FSO with the 
study UP Device. 
Prior to the baseline sinus dilation procedure, the FSO will be assessed under endoscopic 
visualization and the assessment will be recorded on the Endoscopic Scoring Form. Using a 3-
mm olive-shaped frontal sinus suction tip, the patency and FSO diameter assessments will be 
performed. Final subject eligibility will be confirmed based on bilateral stenosis of the FSO on 
endoscopic assessment. NOTE: Physician may use light-assisted or image-guided instrument 
such as a smaller diameter frontal sinus seeker tip to confirm access of each FSO and if the sinus 
is amenable to balloon insertion.  

 
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No other devices, spacer, or packing (with or without steroid) may be used during or after the 
baseline dilation procedure. Aggressive suction and irrigations of the treated site should be 
avoided, as much as possible.  
In subjects in the PK cohort, dilation of the maxillary and/or sphenoid sinus with the same UP 
Device may be performed, if clinically necessary, after the index dilation procedure. In subjects 
in the randomized cohort, dilation of the maxillary and/or sphenoid sinus with a commercially 
available balloon sinuplasty device may be performed, if clinically necessary, prior to 
randomization. No other surgical procedures at baseline will be allowed.  
The steps to be followed for the in-office dilation procedure for this study are as follows: 
1.  Insert a compatible lightwire through the proximal end of the UP Device. 
2. Insert the UP Device into the compatible sinus guide catheter. 
a. If desired, attach the compatible sinus guide catheter handle to the sinus guide 
catheter before insertion of the UP Device. 
3. Insert the sinus guide catheter into the FSO and position the sinus guide catheter tip 
opening toward the FSO (See Section 7.2 Investigational Device for compatible 
accessory devices). 
4. Confirm that the lightwire is in the sinus, then advance the UP Device through the guide 
catheter and position it in the targeted FSO. Note: Under endoscopic visualization, ensure 
that the proximal end of the balloon (yellow single-band marker) is visible outside of the 
frontal sinus ostium. 
5. Inflate the balloon of the UP Device with the compatible inflation device to 12 
atmospheres (atm). 
6. Hold the inflated balloon at 12 atm for a minimum of ~10 s and maximum of ~30 s. 
7. Deflate the balloon.  
8. Reposition the balloon distal to the first inflation site such that the proximal half of the 
balloon is in contact with sinus mucosa, adjacent to the first inflation site.  
9. Repeat steps 5 and 6 to dilate the sinus ostium for a total of 2 inflations in each sinus 
ostium. 
10. Retract the deflated balloon into the guide catheter before removing the dilation system 
out of the nostril (Note: Do not retract the tip of the UP Device beyond the blue tip 
marker on the guide catheter to prevent loss of the drug). 
PK cohort: Subjects will undergo in-office bilateral sinus dilation with the UP Drug-Coated 
Device in the frontal sinuses with 2 inflations per sinus (total of 4 inflations per Device).  
• Repeat steps 1 through 10 for each FSO with the same UP Drug-Coated Device. Note: 
Dilation of the maxillary and/or sphenoid sinus with the same UP Device may be 
performed, if clinically necessary. However, dilation of the maxillary and/or sphenoid 
sinuses must be performed only after dilation of the frontal sinuses. 
• On the day of the baseline procedure, 4 additional blood draws (~ 11 ml at each 
timepoint) will be performed at 0.5 (± 5 min), 1 (± 5 min), 2 (± 10 min) and 4 (± 15 min) 

 
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hours following the end of the baseline procedure, defined as removal of UP Device from 
the nostril after successful dilation of both FSO in each subject.  
Randomized cohort: Subjects will undergo an in-office sinus dilation with the UP Drug-Coated 
Device of the FSO randomized to treatment (2 inflations per device) while the contralateral FSO 
will serve as control and undergo sinus dilation with a UP Control Device (2 inflations per 
device). 
• Steps 1 through 10 will be followed with each frontal side dilated with the assigned UP 
Device.  
Postoperative care 
PK cohort subjects will be required to collect urine samples for 24 hours following the baseline 
procedure. 
After the baseline procedure, subjects in the PK cohort will be allowed and subjects in the 
randomized cohort will be required to use saline sprays/rinses/irrigations starting Day 2.  
PK cohort subjects will not be allowed to use INCS sprays throughout the 30 days follow-up 
duration. Randomized cohort subjects will be allowed to use INCS sprays starting after the 
scheduled Day 14 study visit, if medically necessary.    
Device disposal 
The investigational and compatible accessory devices must be disposed per standard institutional 
practices for biohazard waste. If the UP Device or other compatible accessory devices are 
associated with a device-related AE, malfunction, or failure, all the components should be 
returned to the sponsor for evaluation, as much as possible. For the return of biohazard product, 
the sponsor must be contacted prior to product return for handling instructions. 
Device malfunction and use error 
All potential and suspected device malfunctions and use errors of the investigational device will 
be reported to and reviewed by the sponsor. Any AEs associated with the investigational device 
and/or compatible accessory devices will be recorded in the corresponding CRFs in the EDC 
system. 
11.3 
Follow-Up Phase 
The follow-up period begins immediately post-procedure (once the subject exits the clinic).  
PK cohort 
Each subject will return for up to 6 follow-up visits (see Section 5 Study Flow Diagram and 
Section 6 Schedule of Assessments). 
• Day 1 (24 hours ± 3 hours after the baseline procedure) 

 
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• Day 3 (72 hours ± 3 hours after the baseline procedure) 
• Day 7 ± 2 days 
• Day 14 ± 2 days 
• Day 21 ± 2 days 
• Day 30 ± 3 days 
The protocol-required follow-up assessments through Day 30 will consist of: 
• SNOT-22 questionnaire (at Days 14 and 30) 
• Endoscopic examination, grading and video recording (at Days 7, 14, 21 and 30) 
• Blood sample collection of 11 ml (at Days 1, 3, 7, 14, and 30) 
o All blood draws must occur in the morning and at approximately the same time of 
the day during the follow-up visits. 
Randomized cohort 
Each subject will return for up to 5 follow-up visits for endoscopic grading and video recording 
(see Section 5 Study Flow Diagram and Section 6 Schedule of Assessments).  
• Day 7 ± 2 days 
• Day 14 ± 2 days 
• Day 21 ± 2 days 
• Day 30 ± 2 days 
• Day 60 ± 7 days 
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, and/or 
• Sinus-related adverse events requiring medical evaluation. 
The assessment at an unscheduled visit will consist of: 
• SNOT-22 questionnaire (PK cohort only), and,  
• Endoscopic examination, 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). 

 
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• Leading up to the baseline procedure, a 14-day restriction for use of oral steroids, 
budesonide or other sinus steroid irrigations/rinses or drops, and nebulized steroids 
administered nasally.  
• After the baseline procedure, subjects will be allowed in the PK cohort and required in 
the randomized cohort to use saline sprays/rinses/irrigations starting at Day 2.   
• If infection is suspected at any time during the study, treatment with antibiotics will be 
permitted. 
• Use of intranasal corticosteroid (INCS) sprays is allowed starting after Day 14 visit in the 
randomized cohort, if clinically necessary, and not allowed throughout the 30-day follow-
up period in the PK cohort. 
• Use of other corticosteroids (e.g., oral, parenteral, injections, budesonide or other sinus 
steroid irrigations/rinses or drops, breath powered steroid delivery [e.g. XHANCE™, 
fluticasone proprionate] nebulized steroids administered nasally) will not be permitted 
during the study follow-up unless clinically necessary (see Section 13 Medical and 
Surgical Interventions). 
• If already on such medications, use of orally-inhaled steroids for control of asthma will 
be permitted. 
• Use of corticosteroid-eluting sinus implants (PROPEL®, PROPEL® Mini, PROPEL® 
Contour, SINUVA®) or other nasal packing and spacers is prohibited 14 days prior to 
baseline, during the baseline procedure and through Day 30 in the PK cohort and through 
Day 60 in the randomized cohort. 
• To the extent possible, subjects will be maintained on stable regimens of leukotriene 
inhibitors and/or immunotherapy (e.g., Montelukast, Zafirleukast, Zileuton) for allergies 
throughout the follow-up duration, if currently on such regimens.  
All sinus-related medications will be recorded in the EDC system including their full brand/trade 
or generic names (whichever prescribed), dose, frequency, indication, start and end dates are 
coded using the World Health Organization drug dictionary. 
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, INCS sprays will be allowed starting after Day 14 visit, if clinically 
necessary, for subjects in the randomized cohort and not allowed throughout the 30-day follow-
up period for subjects in the PK cohort. 
Other corticosteroids (e.g., oral, parenteral, injection, budesonide or other sinus steroid 
irrigations, rinses or drops, nebulized steroids administered nasally) will not be permitted unless 

 
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there is a clinically significant increase or persistence in frontal sinus inflammation occurs, 
coupled with subject complaint of sinusitis symptoms that cause subject to request medical 
intervention.  
13.2 
Surgical Intervention 
Surgical intervention (e.g., repeat balloon dilation or sinus surgery, in-office polypectomy) may 
be required in cases where a clinically significant increase or persistence in frontal sinus 
inflammation occurs, coupled with complaints of sinusitis symptoms that cause subject to prefer 
a surgical intervention (e.g. sinus surgery).  
All oral steroid and surgical intervention will be noted on the concomitant medication and 
follow up CRFs (see Section 16.6 Handling Steroid or Surgical Interventions).  
14 ASSESSMENT OF SAFETY 
14.1 
Specifications of Safety Parameters 
Pharmacokinetic analyses 
Plasma concentrations of MF and cortisol at specified time points will be performed. Samples 
will be analyzed with a validated bioanalytical method for both human plasma MF with a lower 
limit of quantification (LLOQ) of 0.25 pg/mL and for cortisol with an LLOQ of 1.00 ng/mL. 
Additionally,  measurement of urinary cortisol excretion 24 hours prior to the baseline procedure 
and 24 hours after the baseline procedure will be analyzed using a validated bioanalytical 
method with a LLOQ of 1.00 ng/mL. 
Adverse event assessment 
Adverse events (AE) for each subject from the time the subject gives informed consent through 
Day 30 in the PK cohort and through Day 60 in the randomized cohort (end of study) will be 
recorded in the EDC system and monitored. Each AE will be evaluated by clinical investigators 
in terms of strength of relationship (i.e., not related, unlikely related, probably related, definitely 
related) to study drug, study device, and dilation 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 with CRS experience a persisting set of symptoms associated with the disease and may 
continue to present with a wide range of symptoms during the recovery process after in-office 
balloon dilation. These may include symptoms such as pain and discomfort, headache, decreased 
sense of smell, crusting, epistaxis, and other symptoms. Patients healing appropriately after in-
office procedure may suffer from acute infections and/or inflammatory exacerbations unrelated 
to the procedure due to the natural course of their CRS. Therefore, clinical investigators will 
evaluate the occurrence of AEs excluding usual post-operative recovery signs and symptoms 
experienced by study subjects, unless corroborated by objective findings and/or requiring 
specific medical or therapeutic interventions (e.g., antibiotics, repeat ESS, etc.). 

 
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Note: The need for medical or surgical intervention in the FSO post-dilation that is captured on 
the endoscopic scoring CRF, will not be considered an AE. Likewise, other endoscopic findings 
such as adhesion/scarring, polyp formation and restenosis of the FSO will not be considered AE. 
14.2 
Classification of Adverse Events 
All adverse events will be reported from the time of consent through study exit.  The relationship 
of all AEs to the investigational device will be categorized into:  
• Definitely related: There is a clear-cut temporal association, and no other possible cause. 
• Probably related: There is a clear-cut temporal association, and a potential alternative 
etiology is not apparent. 
• Unlikely related: The AE does not follow a reasonable temporal association; or causal 
relationship with the drug, device, or procedure involved in the research is unlikely but 
cannot be completely ruled out. 
• Not related: The AE is completely independent of study product 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 related (definitely related, 
probably related) to the study drug, investigational device, accessory device or dilation 
procedure will be categorized as device-related.  
For device-related AE (anticipated or unexpected/unanticipated), the sponsor may request source 
documentation to confirm the relationship of the AE to the investigational or accessory device 
and may review such AE with an independent otolaryngologist, as needed.  
14.3 
Guidelines for Reporting of Adverse Events 
All AEs, regardless of seriousness or relationship to the investigational device and compatible 
accessory devices, will be recorded in the EDC system and will include event description, date 
of onset, investigator’s assessment of severity, relationship to investigational device, 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 pre-existing medical condition that is present at the time of screening will not be reported as 
an AE. The occurrence of 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 the 
investigational or accessory device, 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 investigational or accessory device. 

 
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The investigator should take appropriate measures to follow all AEs until resolution or until 
progression has been stabilized, or until study exit, to ensure the safety of the subjects. If the AE 
continues beyond the last planned visit per protocol and/or the subject withdraws from the study, 
clinical investigators should follow the subjects according to standard of care. 
If a subject decides to withdraw from the study, clinical investigator should follow patients with 
ongoing AEs till resolution according to the standard of care. 
All AEs must be reported to the sponsor based on the following timeline:  
Type of Report 
Reporting Schedule to the Sponsor 
Investigational or accessory 
device-related AE 
Verbal or written report within 10 working 
days 
Patient death 
Verbal report within 24 hours followed by a 
written report within 2 working days 
SAE/SADE/UADE/USADE 
Verbal report within 24 hours followed by a 
written report within 5 working days 
Device malfunctions, device deficiencies and use errors must be reported to the sponsor 
promptly.  
The investigator will report the above to the reviewing IRB per the IRB’s guidelines. The study 
sponsor will be responsible for reporting safety events to the FDA as required per 21 CFR 812. 
All SAEs (SAE/SADE/UADE/USADE) will be followed until satisfactory resolution; until the 
investigator deems the event to be chronic or the adherence to be stable or until the subject exits 
the study. Other supporting documentation of the event may be requested by the sponsor and 
should be provided as soon as possible.  
All device deficiencies including malfunctions, use errors, and inadequate labeling, will be 
reported to appropriate regulatory bodies and Institutional Review Boards (IRBs)/Ethics 
Committees (ECs) as applicable. 
Each AE will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and 
presented based on the system organ class and preferred term. 
15 RISK/BENEFIT ASSESSMENT 
A risk/benefit analysis has been performed, and a summary of the results is provided below. 
15.1 
Potential Risks 
Risks associated with the use of the UP Drug-Coated Device are anticipated to be similar to 
those experienced by patients who undergo balloon dilation of the sinuses with a non-drug 
coated balloon. 

 
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Consequently, the risks potentially associated with the use of the UP Device may include but are 
not limited to the following: 
• Epistaxis 
• Cerebrospinal fluid leak 
• Pneumocephalus 
• Damage of the orbital wall or other ocular structures 
• Impaired or loss of vision 
• Impaired tearing 
• Periorbital cellulitis/edema 
• Infection 
• Facial/nasal pain  
• Facial/nasal discomfort  
• Headache 
Risks or side effects associated with intranasal mometasone furoate are: 
• Nasal irritation 
• Hypersensitivity reaction 
• Intranasal bleeding (epistaxis) 
• Localized infection (bacterial, fungal, or viral) in the nose or pharynx 
• Nasal burning 
• Nasal dryness 
• Susceptibility to secondary infections 
• Glaucoma/elevation of intraocular pressure 
• Cataracts/change in lens opacities 
• Headache 
• Pharyngitis 
Risks associated with steroids in general are: 
• Alteration of the hypothalamic-pituitary-adrenal axis including growth suppression 
• Immunosuppression 
• Hypersensitivity reactions 
• Headache 
• Epistaxis 
• Coughing 
• Vomiting 
• Candidiasis 
• Glaucoma/elevation of intraocular pressure 
• Cataracts/change in lens opacities 
• Arthralgia 
• Myalgia 

 
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Inhaled and intranasal MF is generally well tolerated in clinical trials and any AE are mild and 
generally of short duration with similar incidence to placebo. The proportion of patients 
discontinuing as a result of AEs related to treatment is very low and generally < 2-5% in most 
trials (Asmanex 2005; Dulera 2010; Nasonex 2005).  
Intranasal glucocorticoids may occasionally cause local adverse effects, such as a mild sensation 
of nasal irritation, crusting, dryness, and usually minor epistaxis; however, these are transient 
and do not worsen during long-term treatment. Local mycotic infections and septal perforations 
with prolonged use of nasal corticosteroids are extremely rare and have not been reported for 
mometasone furoate. These findings may be related to the more rapid clearance of the topical 
corticosteroid by the ciliated nasal epithelium (Kyrmizakis 2000; Van Cauwenberge 2005; Vogt 
1979).  
The MF and polyethlene glycol material constituting the balloon-coating has been used 
extensively in the manufacture of the PROPEL Family of Sinus Implants. The polysorbate 
material consistuting the balloon-coating has extensive history of use in medical devices such as 
vascular drug-coated balloons. Either material is not expected to present any new risks. 
Risks associated with blood sample collection may include fainting, redness, pain, bruising, and 
swelling at the site of venipuncture.   
15.2 
Minimization of Potential Risks 
Risks associated with the UP Device are minimized via: 
• The use of medical grade materials that have a long history of use and have been 
characterized and tested to assure biocompatibility 
• Pre-clinical evaluation including bench testing, analytical testing, and animal studies 
• IFU that detail appropriate device preparation and dilation 
• Selection of investigators with adequate experience and qualifications in the treatment of 
CRS 
• Training of the investigators on proper use of the UP Device, the study protocol, 
investigator responsibilities, and human subjects’ protection. Routine subject follow-up 
that includes direct endoscopic visualization of the dilated sinus and surrounding tissue. 
Additionally, risks will also be minimized by including clinical investigators experienced in 
performing balloon dilation procedures and nasal endoscopy. 
15.3 
Potential Risks to Study 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 electronic CRFs or other study-related 
documentation to be provided to the study sponsor. It is the sponsor’s policy to redact any 

 
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subject’s personally identifying information from any documentation sent to Intersect ENT that 
inadvertently contains it.  
15.4 
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 CRS, which 
may provide some indirect health benefits.  
Subjects who receive the UP Drug-Coated Device may benefit from dilation and local delivery 
of the drug that is intended to reduce post-dilation inflammation/edema. Subjects who receive 
UP Control Device may benefit from dilation of sinuses. 
15.5 
Risk/Benefit Conclusion 
Based upon the Risk assessment performed by Intersect ENT, the risk profile is considered 
appropriate and acceptable given the phase of development of the device.  Potential benefits 
associated with the UP Device are expected to outweigh the identified potential risks to the 
patient. 
16 STATISTICAL CONSIDERATIONS 
A formal Statistical Analysis Plan will be prepared prior to the study database lock and formal 
data analysis from the randomized study. Data collected from the PK and randomized cohorts 
will be analyzed separately. Following is a summary of the intended analyses. 
16.1 
Randomization Scheme 
Randomized cohort 
The ratio of left to right sinus assignments will be 1:1. Eligible subjects will be randomized to 
receive the UP Drug-Coated Device in one FSO (Treatment) while the contralateral side will 
receive the UP Control Device (Control). Randomization will be stratified by site and will be 
implemented using the envelope method. The randomization scheme will be generated by an 
independent biostatistician. 
16.2 
Sample Size Calculation 
PK cohort 
The sample size for this cohort was selected without regard for statistical considerations. 
The sample of 5 treated subjects was deemed adequate to assess whether there will be any 
quantifiable systemic exposure to mometasone furoate when delivered via this route of 
administration. 

 
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Randomized cohort 
The sample size calculation is based on the primary efficacy endpoint – the difference in the 
patency grade at Day 30 between the treatment and control sides, as determined by a blinded, 
independent sinus surgeon based on the centralized video-endoscopy review.  
The relevant null and alternative hypotheses are: 
H0: μ = 0 
H1: μ ≠ 0 
where μ is the mean difference in the FSO patency grade at Day 30 between treatment and 
control sides. The study will be considered successful if there is a statistically significant 
difference in mean patency grade in favor of the UP Drug-Coated Device. 
The sample size for this cohort is calculated based on the following assumptions: 
• Expected mean difference of 0.5 between the treatment and control sides in patency grade  
• A standard deviation (SD) of 1.1 for side-to-side difference in the mean patency grade 
• Target power of ≥ 90% 
• Type I error rate: α = 0.05, 2-sided 
A mean difference of 0.5 between the treatment and control sides in the patency grade is 
considered clinically meaningful.  Based on standard formulas for a 1-sided t-test, a sample size 
of 53 subjects provides at least 90% power to detect a difference of 0.5 in mean patency grade. 
Assuming 25% subjects with non-evaluable data on one or both sides, an additional 17 subjects 
will be enrolled for a total of 70 subjects in the randomized cohort.  
16.3 
Analysis of Primary Endpoints 
PK cohort 
The primary efficacy endpoint is the number of successful balloon dilations, which will be 
reported with descriptive statistics. The left and right sides of each subject will be considered 
independent, and each subject is expected to contribute up to 2 observations. The study will be 
considered successful if ≥ 80% of attempted FSO are dilated successfully with no USADE 
related to the investigation device. A successful FSO dilation is one in which the physician has 
inserted the UP Drug-Coated Device into the targeted FSO, followed by 2 consecutive, complete 
inflations of the balloon. 
Continuous data from the plasma MF, plasma cortisol and 24-hour urinary cortisol 
concentrations will be expressed using descriptive statistics, including but not limited to, means, 
standard deviations, medians, ranges and, where appropriate, coefficient of variation (%). 

 
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Randomized cohort 
The primary efficacy endpoint is the difference in the patency grade between treatment sides at 
Day 30 as determined by an independent, blinded sinus surgeon based on the centralized video-
endoscopy review. 
The primary efficacy endpoint will be analyzed using the paired t-test.  
16.4 
Analysis of Secondary Endpoints  
Endoscopic and patient-reported outcome measures and change from baseline in these measures 
(PK cohort only) will be summarized.  Continuous data will be expressed as means, standard 
deviations, medians, ranges and, where appropriate, 95% confidence intervals (CI) for the mean 
assuming a normal distribution. The paired t-test will be conducted to assess side-to-side 
differences. Categorical data will be expressed as counts and percentages and, where 
appropriate, 95% CI. To compare the need for post-dilation medical or surgical interventions 
(paired binary outcomes) at each timepoint, McNemar’s test will be used. Analyses will be 
presented for each time point.  
To support potential product labeling claims, a subset of secondary endpoints will be identified 
and analyzed using appropriate methods for controlling for family-wise type-1 error rate.  This 
will be detailed in the statistical analysis plan prior to database lock for the randomized cohort.  
16.5 
Analysis of Safety Measures 
The incidence of AEs and SAEs– including investigational device-related AEs, USADE – will 
be tabulated for the PK (through Day 30) and randomized cohorts (through Day 60) separately. 
16.6 
Handling Steroid or Surgical Interventions 
Use of clinically necessary corticosteroids (e.g., oral, parenteral, injection, budesonide or other 
sinus steroid irrigations/rinses or drops, nebulized steroids administered nasally) or surgical 
intervention (including repeat balloon dilation for the FSO) during the study will be recorded and 
tabulated.  
16.7 
Sensitivity Analysis for the Primary Efficacy Endpoints 
Since the primary efficacy endpoint in the randomized cohort is determined by an independent 
blinded sinus surgeon based on review of video-endoscopies taken at Day 30, interventions 
performed by clinical investigators prior to Day 30 can potentially confound the primary efficacy 
outcome. Therefore, a sensitivity analysis will be performed to test the robustness of the efficacy 
conclusion to actual interventions given. In this analysis, data imputations will be performed as 
follows: 
• If prior to Day 30, a clinical investigator indicates on the Endoscopic Scoring Form that 
either frontal recess/FSO required oral steroids or surgical intervention, and such 
intervention was actually given, then the grades given by the independent reviewer will 

 
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be replaced by the grades given by the clinical investigator at the visit preceding such 
intervention. 
• If oral steroids were actually prescribed for reasons other than either frontal recess/FSO, 
then the grades given by the independent reviewer will be replaced by the grades given 
by the clinical investigator at the visit preceding commencement of oral steroids (prior to 
Day 30). 
Additional sensitivity analysis may be performed to assess the sensitivity of the primary efficacy 
conclusion to patterns of missing data. This will be detailed in the statistical analysis plan.  
16.8 
Analysis Populations 
PK cohort: The PK population will consist of all subjects in the safety population with at least 
one non-missing and eligible plasma concentration value.  
Safety population will consist of all subjects and sinuses exposed to investigational device with 
successful dilation of at least one FSO. 
Randomized cohort: All primary analyses will be conducted on the intent-to-treat population. 
Additional analyses may be performed on the per-treatment-evaluable population. 
• Intent-to-Treat (ITT) population will consist of all subjects and sinuses where a sinus 
dilation was attempted. An attempt occurs when the physician introduces the UP Device 
into the subject’s nostril with the intent of dilation. Subjects and sinuses will be analyzed 
according to randomization assignment.  
• Per-Treatment-Evaluable (PTE) population will consist of all randomized patients and 
sinuses which have received the assigned study device in the target sinus, who have no 
major procedural protocol deviations, and for whom follow-up data are available. 
If a subject decides to discontinue from the study, every attempt will be made to continue to 
collect the safety and efficacy data according to the protocol procedures. 
17 STUDY MANAGEMENT 
17.1 
Ethical Considerations 
The rights, safety and well-being of subjects shall be protected in accordance with the ethical 
principles based in the Declaration of Helsinki and consistent with ISO14155, 21 CFR Parts 11, 
50, 54, 56, and 812 Good Clinical Practice, all IRB requirements and all applicable local laws 
and requirements. 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.  

 
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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 
(E6), Clinical investigation of medical devices for human subjects – Good clinical practice 
(BS EN ISO 14155) and other applicable local and federal (e.g., 21 CFR Parts 11, 50, 54, 56, 
and 812) regulations, including the archiving of essential documents. A list of the names, 
locations, and chairpersons of all IRBs (including actions taken by each IRB on the protocol) 
that have been or will be asked to review the protocol will be kept on file. Qualified personnel 
who participate in the conduct of this clinical trial will be qualified by education and/or 
experience and trained to 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 clinical investigators with training on use of the 
UP Device 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 and Human Subjects Protection 
• Instructions for use 
• Investigator responsibilities, including reporting requirements  
• Monitoring and auditing 
• CRF completion guidelines 
• EDC system 
• Electronic recordkeeping 
• Endoscopic grading scales, recording and video uploading 
• Investigational device accountability procedures 
• Protection of subject confidentiality 
New members of the investigation site team may be added from time to time at new or existing 
sites. New personnel should only start their assignment after receiving adequate training in the 
clinical investigation requirements and this training shall be documented. The names, initials, 
signatures, functions, and designated authorizations of new site personnel shall be documented. 
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 (IRB) 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 

 
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procedures and assessments, and investigational device 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 trained and qualified Clinical Research Associates 
(CRAs) from the sponsor and contract CRAs who will be trained and qualified by the sponsor. 
Study sites will be visited regularly to ensure that the study is conducted in compliance with 21 
CFR Parts 11, 50, 54, 56, 812, ISO 14155, the study protocol and other applicable regulations. 
Study monitors will also ensure that the data reported in the 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. A detailed monitoring plan will be developed and 
maintained by the sponsor.  
17.2.4 
Data Management Responsibilities 
Data management will be performed by the sponsor. 
Electronic data capture 
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’. The EDC will be validated and verified prior to use, and validation and 
verification and release documentation will be maintained on file by the study sponsor. 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.  

 
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17.2.5 
Investigational Device Accountability 
An appropriate number of the investigational devices, the UP Drug-Coated Device and UP 
Control Device, will be provided to the study sites. The sites maintain the investigational devices 
in a locked, secure location. Only clinical investigators participating in the study will have access 
to the investigational device. Dispensing of investigational device will be documented by 
authorized personnel. Each batch of the investigational device will be assigned a serial/lot 
number for tracking purposes.   
Investigational devices received by the clinical site will be logged in by the site personnel on 
inventory logs and/or the EDC system. Final reconciliation will be completed at each site before 
or during site closure. Any unused inventory of the investigational device will be returned to the 
sponsor at the direction of the sponsor or at the close of the study. At the end of the study, 
overall study final device reconciliation will be completed internally by the sponsor. 
17.3 
Blinding 
17.3.1 
Randomization 
Randomization assignment will be stratified by site, will follow a blocked scheme with blocks of 
varying sizes, and will be performed using the envelope method. After subjects meet the study 
entry criteria, have been anesthetized, and final eligibility confirmed, site personnel will open the 
assigned randomization envelope for that particular subject.   
17.3.2 
Blinding 
The treatment and control devices are randomly designated with a device code (e.g.: Device C 
and Device D) and do not contain any identifying information regarding the treatment or control 
device. The information inside the randomization envelope will indicate which frontal sinus side 
receives which device code (e.g.: C or D). After the first side is treated with the assigned device, 
that device will be discarded before opening the device assigned to the contralateral side, so that 
no side-by-side comparison of the two devices is made by the clinical investigators or clinical 
staff. 
Hence, the following personnel will be blinded to treatment assignment: 
• Research coordinators at the site who have various responsibilities in conducting the study 
including assisting in baseline dilation procedure, handling randomization assignment, 
maintaining investigational product accountability records, and complete AE reports.  
• Sponsor representatives who serve as a resource and provide guidance for clinical 
investigators and clinical staff on procedure with the investigational devices or during patient 
follow-up.  
• Clinical Research Associates from Intersect ENT and its sub-contractors (as needed), who 
perform routine monitoring activities.  
• The independent reviewer who will grade the Day 14 and Day 30 videoendoscopies.  

 
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17.4 
Investigator Responsibilities 
General responsibilities 
• Each investigator is responsible for ensuring that an investigation is conducted per the signed 
investigator statement (Investigator Agreement/Commitment), the study protocol, and 
applicable regulations; for protecting the rights, safety, and welfare of study subjects under 
the investigator’s care and for the control of drugs/devices under investigation.  
• The investigator shall assure the accuracy, completeness, legibility and timeliness of the data 
reported to the sponsor on the CRFs and in all required reports.   
• Each investigator shall obtain informed consent of each patient to whom the treatment is 
administered in accordance with provisions of 21 CFR Part 50 and ISO14155.  
• Each investigator (designee) is responsible for all applicable IRB requirements under 21 CFR 
Part 56 and ISO14155. 
• Each investigator is responsible for disclosure of financial obligations/conflict of interest to 
the sponsor in accordance with provisions of 21 CFR Part 54. 
• The study will be conducted under 21 CFR 11, 50, 54, 56, 812 and ISO14155.  Investigators 
will be trained on their responsibilities. 
• To ensure proper execution of the study protocol, each investigator will identify a study 
coordinator(s) for this study. Working with and under the oversight of the principal 
investigator, the study coordinator(s) ensures that all study requirements are fulfilled.  
• Each investigator will allow monitoring and auditing of their clinical investigation 
procedure(s) by the sponsor or designee. 
Control and disposition of the investigational device 
An investigator shall administer the investigational device only to subjects under the clinical 
investigator’s personal supervision. The investigator shall not supply the investigational device 
to any person not authorized to receive it. An investigator (or designee) is required to maintain 
adequate records of the disposition of the investigational devices, including dates, quantity, and 
use by subjects. All unopened unused devices must be returned to the 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) per 21 CFR 812. 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 

 
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• Medical records regarding AEs, and investigational device malfunctions and deficiencies, 
use errors (as applicable) 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 applicable/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 
• 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, baseline 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 device 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. 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, the 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 subjects study records, or if 
the records are moved to be under the oversight of a different sponsor-approved investigator or 
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) 
• Investigator agreement/commitment for the participating investigator(s) 
• 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 the sponsor, a site initiation visit has been performed, and the 
sponsor has provided written approval to begin enrollment. 

 
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17.5 
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 the 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 
source documents sent to the sponsor will be tracked, evaluated, and stored using only this 
unique identifier.  
Clinical investigators will maintain confidential study subject lists identifying all enrolled 
subjects. The clinical 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. 
17.6 
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/device presents an unreasonable and significant risk to subjects (the 
sponsor may terminate the study immediately) 

 
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• Persistent non-compliance with the study protocol 
• Persistent non-compliance with the applicable ethics committee or regulatory 
requirements 
• Sponsor decision to terminate study 
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. 
17.7 
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. 
17.8 
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. The 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.  

 
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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. A justification of the non-significant risk determination of the study and any supporting 
information, as necessary, will be provided to the IRB under 21 CFR 812.2(b). Clinical 
investigators must also obtain renewal of IRB approval throughout the duration of the study. 
Clinical investigators are responsible for fulfilling any conditions of approval imposed by the 
reviewing IRB, such as regular reporting, study timing, etc. Clinical investigators will provide 
the study sponsor with copies of such approvals and reports. 
Other investigator reports 
Clinical investigators are responsible for notifying the sponsor of the following: 
Type of Notification 
Timeline 
Withdrawal of IRB Approval 
Verbal report within 24 hours followed by a 
written report within 5 working days 
Informed Consent NOT Obtained 
Verbal or written report within 24 hours of 
becoming aware 
Notifications must identify subjects using the unique study identifier to protect subject’s 
confidentiality. 
17.9 
Final Clinical Study Report 
A final clinical study report (CSR) will be prepared by the study sponsor and provided to the 
regulatory agency, as needed.  
17.10 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. Co-authorship will be granted to the national investigator and to 
principle investigators from each study site based on enrollment contribution. 
 

 
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18 APPENDIX 1: LIST OF CORTICOSTEROID MEDICATIONS 
Trade Name 
(alphabetical order) 
Generic Name 
Route of Administration 
Budesonide 
Pulmicort Respules 
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 
Intranasal sprays 
Kenalog 
Triamcinolone 
Triamcinolone Acetonide 
Intramuscular 
Subcutaneous 
Submucosal 
Mometasone  
Mometasone furoate 
Nasal irrigations 
Intranasal sprays 
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.  
 
 

 
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