Rates of Middle Meatus (MM) Synechiae Formation Post Endoscopic Sinus Surgery (ESS): A Double-blind Randomized Controlled Study Comparing Silastic and Restora™ Steroid Eluting MM Spacer
Phase: PHASE3
Conditions: Sinusitis
Sponsor: Cedars-Sinai Medical Center

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TITLE PAGE 
Title: 
Rates of Middle Meatus (MM) synechiae formation post Endoscopic 
Sinus Surgery (ESS): a double-blind randomized controlled study 
comparing Silastic and Restora™ steroid eluting MM spacer  
Study Design: 
Double blinded, placebo controlled, randomized 
Investigator: 
Martin L. Hopp, MD 
Sub-investigator 
Arthur Wu, MD 
Clinical Research Site: 
Tower ENT, 8631 W Third St., Suite 440E 
Los Angeles, CA. 90048 
IRB # 
Pro00039737 
Protocol Date: 
August 18, 2015 
Revision: 
B 
 
 
 
 
CONFIDENTIAL STATEMENT 
This document contains proprietary and confidential information of SinuSys, Corp.  
Acceptance of this document constitutes agreement by the recipient that no previously 
unpublished information contained herein will be published or disclosed without the prior 
written approval of SinuSys, Corp. with the exception that this document may be disclosed 
to study personnel under your supervision who need to know the contents for conducting the 
study and appropriate Institutional Review Boards (IRBs) under the condition that the 
personnel have agreed to keep this information confidential. The foregoing shall not apply 
to disclosure required by governmental regulations or laws; however, SinuSys, Corp. shall 
be promptly notified of any such disclosure. 
 
 
 
 
 
 
 
 
 

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1 
PROTOCOL SYNOPSIS 
Title: Rates of MM synechiae formation post ESS: a double-blind randomized controlled study comparing 
Silastic and the Restora™ steroid eluting MM spacer 
Primary Objective: 
This study is designed to evaluate basic device usability and confirm safety and effectiveness of the Restora™ 
Steroid eluting spacer as compared to a Silastic spacer. 
Background/ Rationale: 
Endoscopic sinus surgery (ESS) is the gold standard surgical intervention for chronic rhinosinusitis that is not 
adequately controlled with maximal medical therapy.  
In some patients, underlying inflammation (discharge, edema and polyposis), compounded by inflammation 
caused by surgical trauma may lead to an uncontrolled healing response, which results in the synechiae 
formation in the middle meatus (MM). 
Incidence of synechiae formation varies in literature and ranges between 4-35%.  Presence of middle meatal 
synechiae can impair sinus drainage, promote sinusitis, and limit endoscopic visualization of the sinus cavities 
postoperatively. This may result in difficulty in performing postoperative routine endoscopic debridement and 
examination, which is paramount to a successful outcome from ESS. Spacers are often inserted during surgery 
between nasal mucosal surfaces to prevent synechiae. 
The aim of this study is to see if a steroid-impregnated spacer is more effective at reducing  inflammation after 
sinus surgery than a Silastic spacer. 
Study Population: Patient suffering from chronic rhinosinusitis in need of ESS 
Number of Centers: 2-3 
Number of Subjects: 
A total of 49 patients will be treated.  
Test article: 
Restora  Spacer material loaded with Mometasone Furoate  
Study Design: 
This is a double-blind randomized controlled study of 49 patients with chronic rhinosinusitis that require ESS.   
Screening 
In the screening period, inclusion/exclusion criteria for the study participation will be checked. Subjects who 
satisfy these criteria will be invited to participate in the study. Their consent will be recorded. As a standard of 

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care, all patients will fill out the validated SNOT-22 quality of life outcome questionnaire at this pre-op visit. 
Blinding 
The study will be double-blinded. Each patient will be his or her own control. The Silastic spacer will be 
placed on one side and the steroid-eluting spacer will be placed on the other. Neither the patient nor the 
assessor will know on which side the respective spacer is placed. The PI at the primary site will be the blinded 
assessor.  
 
Procedure and follow up 
Patient will undergo ESS and the spacers will be placed in the operating room upon procedure completion. 
Subjects will return to clinic after 6-8 days to have the spacers removed. The removed spacer materials will be 
shipped to SinuSys for residual steroid content analysis. After the initial visit, patients are seen again in clinic 
at 35 and 90 days postoperatively. At each visit endoscopic videos will be collected to enable scoring, as 
detailed in the endpoint section below.  As a standard of care all patients are treated with oral antibiotics 
(Clavulin or Clindamycin if allergic to Penicillin) while they have spacers inserted into their nose. 
The detailed study schedule is provided in Appendix A. 
Projected Study Timelines 
Anticipated Total Study Duration:  Enrollment – 1-2 months, Follow up 3 months. 
Study Endpoints 
• 
Primary Endpoint 
o 35 day sinonasal mucosal inflammation assessed by rigid endoscopy and graded on Lund-
Kennedy sinus mucosal endoscopic staging system 
• 
Secondary Endpoints 
o 90-day sinonasal mucosal inflammation assessed by rigid endoscopy and graded on Lund-
Kennedy sinus mucosal endoscopic staging system 
o 35 and 90-day intraocular pressure (IOP) assessed using applanation tonometry and compared 
to baseline IOP obtained preoperatively 
o 35 and 90-day post ESS incidence of middle meatal synechiae  
o 90-day Sinonasal Outcomes Test-22 (SNOT- 22) scores  
o 35-day frequency of postoperative interventions, including lyses of adhesions and 
debridement.   
o 35-day frequency of oral steroid rescue  
o 35 days middle turbinate position  
Inclusion Criteria 
1) Age between 18 and 75 years   
2) Diagnosis of chronic rhinosinusitis (CRS), per current guidelines  
3) Patients who need to undergo primary bilateral complete endoscopic sinus surgery 
4) Subject has the ability to follow the study instructions, is willing to be available on the specific required 
study visit days, and is willing to complete all study visit procedures and assessments 

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5) Subject must understand the research nature of this study and sign an informed consent prior to the 
performance of any study-specific procedure or assessment 
Exclusion Criteria 
1) Subject is pregnant or breast feeding  
2) Patients with sino-nasal tumors 
3) Patients solely undergoing nasal septal reconstruction 
4) Patients with previous history of endoscopic sinus surgery 
5) Cystic fibrosis or syndromic patients 
6) Patients with autoimmune diseases 
7) Patients who have taken oral steroids less than 30 days prior to surgery 
8) Patients with a history or diagnosis of  glaucoma or ocular hypertension 
9) Any other circumstance or condition that in the Investigator’s opinion causes the subject to be an 
inappropriate candidate for participating in this study 
Statistical Consideration 
This study is designed to evaluate basic device usability and confirm safety and effectiveness of Steroid 
Impregnated Spacer.   There is no success criteria set  based on statistical calculation.  
 
 

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2 
TABLE OF CONTENTS 
 
TITLE PAGE .......................................................................................................................1 
1 PROTOCOL SYNOPSIS ..............................................................................................2 
2 TABLE OF CONTENTS ...............................................................................................5 
3 ABBREVIATIONS .......................................................................................................7 
4 INTRODUCTION .........................................................................................................8 
4.1 
Literature review ..........................................................................................8 
5 RISK ASSESSMENT ....................................................................................................9 
6 STUDY OBJECTIVE ..................................................................................................10 
7 RESTORA AND SILASTIC SPACERS DESCRIPTION ..........................................10 
7.1 
Preclinical data ...........................................................................................11 
7.2 
Clinical data ...............................................................................................12 
8 STUDY DESIGN AND ENDPOINTS ........................................................................12 
8.1 
Inclusion Criteria .......................................................................................12 
8.2 
Exclusion Criteria ......................................................................................13 
8.3 
Blinding......................................................................................................13 
8.4 
Study Procedures .......................................................................................13 
8.5 
Screening/Enrollment Visit ........................................................................13 
8.6 
Screening Procedures .................................................................................13 
8.7 
Treatment visit ...........................................................................................14 
8.8 
Follow-up visits .........................................................................................14 
8.9 
Unscheduled Visits ....................................................................................14 
9 SUBJECT DISCONTINUATION ...............................................................................14 
10 RISK/BENEFIT ASSESSMENT ................................................................................15 
10.1 
Potential Risks ...........................................................................................15 
10.2 
Potential Benefits of Study Participation ...................................................17 
10.3 
Risk/Benefit Conclusions...........................................................................17 

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11 ADVERSE EVENTS / COMPLICATIONS ...............................................................17 
11.1 
Serious Adverse Event (SAE)/Unanticipated Adverse Device Effect (UADE) 
Definition ...................................................................................................17 
11.2 
Adverse Event/Adverse Device Effect Relationship to Study Device ......19 
11.3 
Procedure for Recording and Reporting Adverse Device Effects .............19 
11.4 
Procedures for Reporting a Serious Adverse Event/Unanticipated Adverse 
Device Effect .............................................................................................19 
12 STATISTICAL PLAN .................................................................................................20 
12.1 
Sample Size ................................................................................................20 
12.2 
Analysis Populations ..................................................................................20 
12.3 
Statistical Analyses ....................................................................................20 
13 ADMINISTRATIVE CONSIDERATIONS ................................................................21 
13.1 
APPLICABLE REGULATIONS/STANDARDS/Declaration of Helsinki21 
14 IRB REVIEW ..............................................................................................................21 
15 INFORMED CONSENT .............................................................................................21 
16 SUBJECT CONFIDENTIALITY ................................................................................22 
17 STUDY DOCUMENTATION, CRF’S AND RECORD KEEPING ..........................22 
17.1 
Investigator Files/Retention of Documents ...............................................22 
18 STUDY MATERIALS ACCOUNTABILITY ............................................................22 
19 QUALITY CONTROL AND ASSURANCE .............................................................23 
20 REFERENCES ............................................................................................................24 
21 APPENDIX A ..............................................................................................................26 
SCHEDULE OF EVENTS ....................................................................................26 
 
 
 
 
 
 
 
 
 

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3 
ABBREVIATIONS  
AE 
Adverse Event 
CRF 
CRS 
Case Report Form 
Chronic  Rhinosinusitis 
CFR 
Code of Federal Regulations 
FDA 
ESS 
Food and Drug Administration 
Endoscopic Sinus Surgery 
ICH 
International Conference on Harmonization 
ITT 
MM 
Intent To Treat 
Middle Meatus 
PP 
SAE 
UADE 
 
Per Protocol 
Serious Adverse Event 
Unanticipated Adverse Device Effect  
 
 
 
 
 

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4 
INTRODUCTION 
4.1 
Literature review  
Endoscopic sinus surgery (ESS) is the gold standard surgical intervention for chronic rhinosinusitis that is 
not adequately controlled with medical therapy. Synechiae formation in the middle meatus is the most 
common complication of endoscopic sinus surgery (1).  Synechiae describes the adhesion of two 
opposing mucosal surfaces in the nasal cavity that can cause scarring and obstruction of the nasal passage. 
Incidence of synechiae formation varies in literature and ranges between 4-35 % (2, 3, and 4). Presence of 
middle meatal synechiae can impair sinus drainage, promote sinusitis, and limit endoscopic visualization 
of the sinus cavities postoperatively. This may result in difficulty in performing postoperative routine 
endoscopic debridement and examination, which is paramount to a successful outcome from ESS (5).  
 
To prevent synechiae formation, numerous studies have been published evaluating the effectiveness of 
absorbable and non-absorbable spacers placed in the middle meatus for 1-2 weeks postoperatively.  The 
spacer is meant to prevent contact between the denuded surfaces of the middle turbinate and the lateral 
nasal wall during re-epithelialization.  In general, non-resorbable spacers that have been used include 
sponges, cotton gauze and plastic sheets. Of these, Silastic Silicone sheets have been used in a number of 
hospitals across the US and Canada.  Lee (6) and Baguley (7) have demonstrated the effectiveness of 
Silastic spacers in reducing the risk of synechiae formation to between 0-6 % (6, 7).   There are also a 
number of resorbable spacers that are in use, which are preferred by some physicians because there is 
minimal need to remove the packing materials as they naturally are removed or resorbed during the 
healing period.  
 
In a recent meta-analysis, Lee et al (8) has revealed that usage of middle meatal spacers (absorbable and 
non-absorbable) did not decrease the rate of synechiae formation to a statistically significant degree 
compared to not using any spacer. However, when subgroup analysis was performed, non-absorbable 
spacer usage demonstrated a statistically significant lower incidence of synechiae compared to no spacers 
(6).  This can be explained in part by an inherent capability of the absorbable spacer material to degrade 
to smaller size particulates that, if caught in the healing tissue, could illicit local inflammatory response to 
slow down the healing and cause further synechiae formation.  This mechanism was demonstrated by 
Maccabee et al (9) in a rabbit model, where fibers of the absorbable spacer became incorporated into 
healing mucosa and increased the extent of the inflammatory response and formation of fibrosis.   
 
To improve outcomes, physicians have attempted to load steroids such as Triamcinolone  (10, 15) and 
antibiotics such as Neosporin (11) into nasal packing and/or stents. However, residence of the drug in the 
intended treatment space is minimized as the drug, which is not bound to the spacer, quickly releases and 
may not remain long enough to impact inflammatory response.  A Mometasone Furoate coated stent 
(Propel™), manufactured by Intersect ENT, is currently the only drug coated nasal stent that has a claim 
of longer sustained release.  In a randomized, controlled, double-blind trial, Marple et al (12) found that 
this Mometasone Furoate steroid-eluting bio-absorbable stent  could significantly improve postoperative 
outcomes compared to a non-steroid eluting placebo arm with the same stent.  Zhao et al (13) conducted a 
systematic review of the efficacy of this steroid-eluting stent (Propel) vs inert (both resorbable and non-

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resorbable) spacers and again confirmed that there are lower rates of synechiae formation in the steroid-
eluting treatment groups. However, anecdotal evidence, based on discussion with a number of surgeons in 
the field, suggests that a drug-loaded resorbable spacer may be subject to the same issues as non-drug-
loaded resorbable spacers, namely late stage degradation of the material that can cause a secondary spike 
of the inflammatory cascade, requiring additional surgical intervention to remove the remaining debris.  
 
Therefore, it has been hypothesized that a steroid eluting non-absorbable spacer may provide optimal 
benefit for the patient’s outcome. The Restora™ spacer is made of a biocompatible non-resorbable 
material that is expected to deliver up to 370 µg of Mometasone Furoate. The steroid elutes out of the 
spacer and onto the surrounding mucosal tissue during the 6-8 day period during which it is retained.    
 
This study is designed to evaluate basic device usability and confirm safety and effectiveness of the 
Restora™ Steroid eluting spacer as compared to the standard of care Silastic Silicone spacer. 
5 
RISK ASSESSMENT 
The Restora Nasal Spacer has the primary mode of action of being a mechanical support to physically 
separate opposing mucosal surfaces and thereby reduce the potential for synechiae formation.  The 
addition of Mometasone Furoate, a well-known and well characterized anti-inflammatory with a long 
history of use in the nasal cavity, is intended to reduce post-surgical inflammation during the natural 
healing process.    
 
There are two potential sources of risks that can be derived from the use of the Restora spacer: 1) due to 
the spacer material and shape and 2) due to the drug loaded onto the spacer. 
 
The risks associated with the spacer material itself is considered minimal as the material is biocompatible 
for its intended use and the material shape (thickness, and area) is similar to that of the standard Silastic 
Silicone sheet that is used surgically.   
 
The risk associated with the drug is comparable to that with the use of the commercially available 
Intersect Propel Stent as the amount of drug that is expected to be released from Restora™ is similar to 
that released from Propel, 370µg.  In addition, the anti-inflammatory steroid, Mometasone Furoate (active 
ingredient in Nasonex) has been approved for intra-nasal delivery since 1997.  The recommended daily 
dose delivered for treatment of nasal allergies is 2 sprays per nostril per day and for polyposis is 2 sprays 
per nostril twice a day. Each spray dose is 50 µg. Therefore, the total maximum recommended dose for 
the patient is 400 µg per day, and total of 2,800 µg over a 7 day period. Topical Mometasone Furoate 
spray has also been administered post ESS to help reduce post surgical inflammation at the same dose 
prescribed for allergies, namely 400 µg/day (14).  Compared with this spray dose, the dose of 
Mometasone Furoate delivered by Restora is at least 7 fold less than that for the Nasonex. 
 
The Restora Nasal Spacer is considered a non-significant risk device because it does not meet the criteria 
specified by FDA for a significant risk device.  Reference FDA Guidance “Information Sheet Guidance 
for IRBs, Clinical Investigators, and Sponsors – Significant Risk and Non-Significant Risk Medical 
Device Studies” dated January 2006: 

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• 
Restora is not intended as a permanent implant and does not present a potential for serious 
risk to the health, safety, or welfare of a subject;  
• 
Restora is not purported or represented to be for use supporting or sustaining human life and 
does not present a potential for serious risk to the health, safety, or welfare of a subject;  
• 
Restora is not for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health and does not present a potential 
for serious risk to the health, safety, or welfare of a subject; and  
• 
Does not otherwise present a potential for serious risk to the health, safety, or welfare of a 
subject  
 
This study will be conducted in accordance with requirements specified in 21 CFR 812.2(b). 
 
Risks associated with the use of the SinuSys Restora Spacer are anticipated to be similar to those 
experienced by patients undergoing placement of other non-resorbable spacers and less than that of 
Propel due to its non-resorbable nature.  The potential clinical benefits of the Restora Spacer are 
believed to exceed any residual risks associated with the use of the Restora Spacer. 
 
6 
STUDY OBJECTIVE 
The main objective of the trial is to evaluate basic device usability and confirm safety and effectiveness of 
Restora™ Mometasone Furoate eluting spacer as compared to a Silastic spacer. 
 
7 
RESTORA AND SILASTIC SPACERS DESCRIPTION 
 Silastic spacer is an inert plastic that can be shaped to fit the operative field. A soft, pliable, 0.04 -inch-
thick polymeric Silastic sheet, shaped into an inverted U by suturing the middle of the spacer to keep the 
shape, will be placed between the middle turbinate and lateral nasal wall. Image of Silastic spacer placed 
in the Middle Meatus is shown in figure 1. 
 
 
Figure 1: Silastic Nasal Spacer placed in the Middle Meatus of the nose. 
 
Restora spacer is composed of Tecophilic HP-93A-100 resin (Lubrizol Inc) that has been extruded,  cut to 
the desired shape, shaped, packaged, and finally exposed to a terminal gamma irradiation (25-40 kGy) 
sterilization process to reduce bioburden. The material is provided in a boot shape geometry and has 

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thickness of approximately 0.84mm (Figure 1). The Restora spacer is pre-shaped into an inverted U  to 
keep the shape before placement between middle turbinate and lateral nasal wall. 
 
 
Figure 2: Restora Nasal Spacer placed in the Middle Meatus of the nose. 
 
Mometasone Furoate will be loaded into the spacer using proprietary SinuSys protocol to target up to 370 
µgm delivery in-vivo. Once loaded, the spacer is capable of eluting drug over its residency time in the 
middle meatus.   
 
7.1 
Preclinical data 
 
The Restora spacer has been tested in the USP dissolution apparatus in comparison to Intersect Propel 
stent.  In order to do the side by side comparison, Restora spacer was loaded with the same amount of MF 
as Propel, 370 µgm. Figure 3 below demonstrates controlled sustained release of Mometasone Furoate as 
% of total drug loading.   
 
 
 
 
 
 
Figure 3:  Cumulative Mometasone Furoate Release from Propel Mini compared to Restora Nasal spacer 

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This graph demonstrates that Restora platform has capacity to provide longer sustained release than the 
Propel product under same test conditions. 
 
7.2 
Clinical data 
Initial experience with Restora Spacer has been completed on 23 patients, as part of on-going study by 
Dr. Amin Javer at University of British Columbia (Amin Javer MD, Principal Investigator), under similar 
protocol. In this study, patients undergoing ESS procedure received one Restora Spacer and one Silastic 
spacer, placed bi-laterally, post ESS. The spacers were removed at day 6 post surgery.  There were no 
adverse events reported.   
 
Spacers were sent to SinuSys for MF content analysis. The average amount of MF loaded on the spacers 
was 483.64±25.62 µgm. Average amount of drug remaining on the spacers was 418.83±25.65 µgm.  
Total amount of drug released was 64.81 µgm, 13% of the dose loaded. 
 
Based on this information,  loading protocol used in this study is adjusted to provide target dose of up to 
370 µgm in vivo. 
 
8 
STUDY DESIGN AND ENDPOINTS 
Approximately 50 patients will receive spacers during their ESS procedures and be followed for 90 days. 
This will require enrolling approximately 60 patients between all of the participating centers to account 
for possible loss-to-follow-up (LTF).  
• 
Primary Endpoint 
o 35-day sinonasal mucosal inflammation assessed by rigid endoscopy and graded on 
Lund-Kennedy sinus mucosal endoscopic staging system 
• 
Secondary Endpoints 
o 90-day post ESS incidence of middle meatal synechiae  
o 35 and 90-day sinonasal mucosal inflammation assessed by rigid endoscopy and graded 
on Lund-Kennedy sinus mucosal endoscopic staging system 
o 35 and 90-day intraocular pressure (IOP) assessed using applanation tonometry and 
compared to baseline IOP obtained preoperatively 
o 35 and 90-day post-ESS incidence of middle meatal synechiae  
o 90-day  validated Sinonasal Outcomes Test-22 (SNOT- 22) scores  
o 35-day frequency of postoperative interventions, including lyses of adhesions and 
debridement.   
o 35-day frequency of oral steroid rescue  
o 35 days middle turbinate position  
8.1 
Inclusion Criteria 
1) Age between 18 and 75 years 

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2) Diagnosis of chronic rhinosinusitis (CRS), per current guidelines  
3) Patients who need to undergo primary bilateral complete endoscopic sinus surgery 
4) Subject has the ability to follow the study instructions, is willing to be available on the 
specific required study visit days, and is willing to complete all study visit procedures 
and assessments 
5) Subject must understand the research nature of this study and sign an informed consent 
prior to the performance of any study-specific procedure or assessment 
8.2 
Exclusion Criteria 
1) Subject is pregnant or breast feeding  
2) Patients with sino-nasal tumors 
3) Patients solely undergoing nasal septal reconstruction 
4) Patients with previous history of endoscopic sinus surgery 
5) Cystic fibrosis or syndromic patients 
6) Patients with autoimmune diseases 
7) Patients who have taken oral steroids less than 30 days prior to surgery 
8) Patients with a history or diagnosis of glaucoma or ocular hypertension 
9) Any other circumstance or condition that in the Investigator’s opinion causes the subject 
to be an inappropriate candidate for participating in this study 
8.3 
Blinding 
The study is double-blinded. Each patient is his or her own control. Neither the patient nor the assessor 
will know on which side the respective spacer is placed. The Principal Investigator will be the blinded 
assessor. The choice of spacer for each side will be randomized using the sealed envelope system. 
8.4 
Study Procedures 
A table of study assessments is presented in Appendix A. 
 
8.5 
Screening/Enrollment Visit 
All consented subjects will be assigned a unique subject number.  Screening procedures can occur only after 
consent is signed.  Screening and device placement may occur on the same day.  If the placement procedure 
occurs on a different day than the screening/enrollment visit the inclusion/exclusion criteria have to be 
reevaluated.  The device placement attempt must occur within 30 days of initiating screening procedures. 
 
As a standard of care, all patients will fill out the SNOT-22 quality of life questionnaire at this visit. 
 
8.6 
Screening Procedures 
The following screening procedures will be performed before the device placement attempt is initiated: 

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1. Written informed consent prior to conducting any study-specific procedures 
2. Demographic information  
3. Targeted medical history 
4. Medication history including medications for 7 days prior to enrollment 
5. Pregnancy test  
6. Nasal Endoscopy 
7. Any other screening procedures for dilation of intended treatment spaces that are standard of care to 
the investigation site 
8. Review of eligibility criteria (subject failing to meet all inclusion/exclusion criteria are to be recorded 
as Screen Failures) 
8.7 
Treatment visit 
Patients will undergo bilateral ESS procedure. Each patient will receive one Silastic and one Restora 
spacer, placed bilaterally.  
 
As a standard of care all patients are treated with oral antibiotics (clavulin or clindamycin if allergic to 
penicillin) while they have spacers inserted into their nose. 
 
The device(s) can be removed anytime upon the subjects’ request or if the Investigator deems it 
necessary.   
8.8 
Follow-up visits 
 
There will be a total of 3 follow up visits: 6-8 days, 35 days, and 90 days after ESS.  Follow-up visits 
will consist of appropriate standard of care treatment for subjects.  At each follow-up visits a nasal 
endoscopy will be performed and endoscopic videos will be obtained. Any potentially device related 
complications will be assessed, concomitant medication will be recorded. During the follow up period, 
subjects may receive any medication the Investigator deems necessary.  Prescription of a new medication 
will not exclude further participation.  
 
As a standard of care, all patients will fill out the SNOT-22 quality of life questionnaire at their 90 day 
visit. 
 
8.9 
Unscheduled Visits 
 
It is at the discretion of the Investigator to have the subject return to the study site prior to any regular 
scheduled visit if, for example, the subject experienced an adverse event and/or it is in the best interest of 
the subject for whatever reason.  Evaluation of subjects during an unscheduled visit should include a nasal 
endoscopy if possible.  All other evaluation and testing will be decided by the investigator based on the 
presenting issue(s) and should be documented. 
9 
SUBJECT DISCONTINUATION 

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Subjects may be discontinued from the study for any of the following reasons (but are not limited to): 
• 
Adverse event 
• 
Significant protocol deviation  
• 
Subject noncompliance 
• 
Subject voluntary withdrawal 
• 
Investigator judgment (e.g., inter-current medical problem) 
• 
Lost to Follow-up – for a subject to be considered lost to follow-up 3 documented attempts to 
contact the subject shall be made by phone and a certified letter shall be sent.   
A subject may discontinue voluntarily at any time, for any reason during their participation in the study.  
If a subject decides to discontinue participation and withdraw from the study, an attempt shall be made to 
obtain information about any adverse events or reasons for discontinuation.  The investigator may 
withdraw a subject from treatment if, in his/her judgment, it is in the subject’s best interest to do so.  The 
investigator shall record the reason for subject discontinuation on the appropriate CRF.  Discontinued 
subjects may be replaced with another enrolled subject. 
Intent to treat occurs once all eligibility criteria have been met and informed consent has been signed and 
an attempt is made to place the device into the treatment space.  Any discontinued subject will be 
followed for as long as possible and any safety and effectiveness results will be included in the final 
analysis and report. 
 
10 RISK/BENEFIT ASSESSMENT 
10.1 Potential Risks 
There are two potential sources of risks that can be derived from the use of the Restora spacer: 1) due to 
the spacer material and shape and 2) due to the drug loaded onto the spacer. 
 
The risks associated with the spacer material itself is considered minimal as the material is biocompatible 
for its intended use and the material shape (thickness, and area) is similar to that of the standard Silastic 
Silicone sheet that is used surgically.   
 
The risk associated with the drug is comparable to that with the use of the commercially available 
Intersect Propel stent, as the amount of drug loaded on Restora™ is equivalent to that loaded onto Propel 
Stent, 370µgm.  In addition, the anti-inflammatory steroid, Mometasone Furoate (active ingredient in 
Nasonex) has been approved for intra-nasal delivery since 1997.  The recommended daily dose delivered 
for treatment of allergies is 2 sprays per nostril per day and for polyposis is 2 sprays per nostril twice a 
day. Each spray dose is 50 µg. Therefore, the total maximum recommended dose for the spray user is 400 
µg per day and total of 2,800 µg over a 7 day period. Compared with this recommended dose, the dose of 
Mometasone Furoate delivered by Restora is at least 7 fold less than that for the Nasonex. 
 
The potential risks of study participation fall into the following categories:  
 

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Frequent: expected to occur in more than 25% of people (more than 25 out of 100 people) 
Probable: expected to occur in 10-25% of people (10-25 out of 100 people) 
Occasional: expected to occur in 1-10% of people (1-10 out of 100 people) 
Remote: expected to occur in less than 1% of people (less than 1 out of 100 people) 
Incredible: expected to occur in less than 0.1% of people (less than 1 out of 1000 people). 
 
The risks and possible side effects may include the following: 
 
1. Device Risks 
• 
Premature Displacement of spacer post placement – Remote 
• 
Swallowing of spacer – Incredible 
• 
Adherence of crusting to the implant, resulting in or contributing to sensation of 
pain/pressure/headache - Occasional 
• 
Foreign body response, including formation of granulation tissue - Remote 
• 
Choking- Incredible 
2. Drug Risks 
• 
Nasal irritation and burning - Remote 
• 
Intranasal bleeding - Remote 
• 
Localized infection (bacterial, fungal, or viral) in the nose or pharynx – Occasional 
• 
Nasal Dryness - Incredible 
• 
Glaucoma/elevation of intraocular pressure - Incredible 
• 
Cataracts/change in lens opacities - Incredible 
  
3. General Side Effects with Steroids 
• 
Alternation of the HPA axis including growth suppression (steroid modulation) - 
Incredible 
• 
Immunosuppression - Incredible 
• 
Headache - Incredible 
• 
Epistaxis - Incredible 
• 
Coughing - Incredible 
• 
Arthralgia - Incredible 
• 
Myalgia – Incredible 
• 
Fatigue - Occasional 
 
 
 
4.  Nasal Endoscopy is part of routine care associated with rhinosinusitis.  These risks may include 
mild discomfort or light bleeding.  
 
5. The standard risks associated with general anesthesia. 
6. An unexpected risk could emerge. 
 

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Risks associated with the use of the SinuSys Restora Spacer are anticipated to be similar to those 
experienced by patients undergoing placement of other non-resorbable spacers and less than that of Propel 
stent due to its non-resorbable nature.  The potential clinical benefits of the Restora Spacer are believed to 
exceed any residual risks associated with the use of the Restora Spacer. 
 
10.2 Potential Benefits of Study Participation 
There may be no direct benefits of study participation.  However, subjects will undergo an enhanced level 
of clinical scrutiny compared to routine clinical care, which may provide some indirect health benefits.   
 
In addition, there could be a benefit of using a drug-eluting spacer post ESS to decrease rate of synechiae 
formation, and frequency of postoperative interventions, including lyses of adhesions and debridement. 
 
This study is intended to confirm the feasibility of the use of the Restora Nasal Spacer for this purpose. 
10.3 Risk/Benefit Conclusions 
Based upon the Risk/Benefit analysis performed, the benefits associated with the Restora Nasal Spacer is 
expected to outweigh the potential risks to the patient. 
11 ADVERSE EVENTS / COMPLICATIONS 
11.1 Serious Adverse Event (SAE)/Unanticipated Adverse Device Effect (UADE) Definition 
Serious Adverse Event (SAE): A SAE is defined as any untoward medical occurrence that: 
• 
Results in death, 
• 
Is life-threatening, 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in medical or surgical intervention to prevent life threatening illness  
• 
Results in injury or permanent impairment to a body structure or a body function  
• 
Results in persistent or significant disability/incapacity 
Also in the category of SAE is: 
• 
Any other unanticipated serious problem caused by or associated with the device that relates 
to the rights, safety, or welfare of subjects [21 CFR 812.3(s)] 
Important medical events that may not result in death, be life-threatening, or require hospitalization may 
be considered a SAE when, based upon appropriate medical judgment, they may jeopardize the subject or 
may require medical or surgical intervention to prevent one of the outcomes listed above.  Elective 
hospital admission will not be considered an SAE for this study. 
 
Unanticipated Adverse Device Effect (UADE) is any serious adverse effect on health or safety, 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 application; or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects. 

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All SAE/UADEs will be collected from first application of the treatment product at the baseline visit until 
study exit. 

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11.2  Adverse Event/Adverse Device Effect Relationship to Study Device  
The relationship of an event to study device will be documented by the investigator as follows: 
Unrelated:   The event is clearly related to other factors such as the subject’s clinical state, other 
therapeutic interventions or concomitant drugs administered to the subject.  Note, it is not 
necessary to record in the CRFs these unrelated events. 
Possible:   The event follows a reasonable temporal sequence from the time of treatment product 
administration, but could have been produced by other factors such as the subject’s clinical state, 
therapeutic interventions or concomitant drugs. 
Probable:   The event follows a reasonable temporal sequence from the time of treatment product 
administration, and follows a known response pattern to the treatment product. The event cannot be 
reasonably explained by other factors such as the subject’s clinical state, therapeutic interventions 
or concomitant drugs. 
Definite:  The event follows a reasonable temporal sequence from the time of treatment 
product/device administration, follows a known response pattern to the treatment product/device, 
cannot be reasonably explained by other factors such as the subject’s condition, concomitant drugs 
or therapeutic interventions, AND either occurs immediately following treatment product 
administration, improves on stopping the treatment product, or reappears on re-exposure of the 
treatment product/device. 
11.3 Procedure for Recording and Reporting Adverse Device Effects 
All SAEs and all possibly device related AE/ADEs will be collected from first application of the study 
treatment products at the baseline visit until study exit. 
 
Beginning with the first study treatment, the investigator will determine whether any SAEs or possibly 
device related adverse experiences have occurred by evaluating the subject’s signs, symptoms, and other 
test results or assessments.  
 
All SAEs and possibly device related AEs / complications and ADEs (expected or unexpected) which 
occur during the specified study period, whether observed by the investigator or by the subject, and 
whether or not thought to be related to treatment product or to study procedures, will be reported in detail 
on the appropriate CRF and followed until resolution, stabilization, or death, according to Good Clinical 
Practice (GCP).  The record of the SAE/ADE will include a description of the event, start date, stop date, 
duration, outcome, intensity, if it was serious, relationship to treatment product or study procedure (i.e., 
causality), change in dosage or discontinuation of treatment product, if treatment was required and if the 
subject died.  The investigator must verify this information. 
11.4 Procedures for Reporting a Serious Adverse Event/Unanticipated Adverse Device Effect  
It is the responsibility of the Investigators to inform their IRB about serious adverse events or other events 
as required by their IRB procedures and in compliance with the applicable regulations. 
The investigator should inform SinuSys either by phone or email, within 24 hours of the investigator 
becoming aware of the event. SAE/UADEs shall be initially reported to: 

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Name:  
 
 
Janie Mandrusov 
Title: 
 
 
Director, Preclinical and Clinical Development 
Address:       
 
SinuSys Corp, 2468 Embarcadero Way, Palo Alto, Ca 94303 
Telephone:  
 
1-408-410-4411 
Email: 
  
 
emandrusov@sinusys.com 
A full investigation of any SAE/UADE will be conducted by  the Investigator in collaboration with 
SinuSys Corporation.    The Investigator shall report the results of such evaluation to the IRB within 10 
working days after notice of the effect.  Only Unanticipated possibly device related complications will 
need to be considered for possible reporting to the FDA.  Please consult with regulatory counsel for 
guidance. 
If principal investigator determines that an SAE/UADE presents an unreasonable risk to subjects, the 
investigation must be terminated as soon as possible, but no later than 5 working days after the 
investigator makes this determination. 
 
All subjects with an SAE/UADE must be followed up and the outcomes reported. The Investigator should 
supply SinuSys Corporation and the IRB with any additional requested information (e.g., hospital 
discharge summary, autopsy report, pathology report, operative report, terminal medical report, etc). 
12 STATISTICAL PLAN  
12.1 Sample Size 
Up to approximately 50 subjects will be enrolled into the study.  This study is designed to evaluate basic 
device usability and confirm safety and effectiveness of Restora Nasal Spacer.  
There is no success criteria set based on statistical calculation.  
 
12.2 Analysis Populations 
The following subject populations will be created: 
Safety (Safety):  All subjects enrolled who underwent the device placement procedure, regardless of 
outcome. 
Intent To Treat (ITT):  All subjects enrolled who underwent the device placement attempt, regardless of 
outcome. 
Per Protocol (PP):  A subset of the ITT population that excludes subjects with major protocol deviations 
(to be identified prior to data lock). 
The primary efficacy analysis will be carried out on both ITT and PP populations.  
No effort will be made to impute or extrapolate data to replace missing values. 
12.3 Statistical Analyses 

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Appropriate statistical methods will be used to analyze the data.  Descriptive statistics for continuous 
variables will consist of the mean, median, standard deviation, minimum, and maximum values. For 
categorical variables, the number and percentage of each category will be displayed.  
For the primary endpoints the following acceptance criteria had been defined:  
• 
Safety: The study will be considered successful if no Unanticipated Device Adverse Effect 
occurs during device residence time and the overall rate of device related complications is 
clinically acceptable. 
• 
Performance: The study will be considered successful if there is a trend or significant 
difference in primary end point between Restora and Silastic spacer 
 
13 ADMINISTRATIVE CONSIDERATIONS 
13.1 APPLICABLE REGULATIONS/STANDARDS/Declaration of Helsinki 
The investigator will ensure that this study is conducted in full conformance with the principles of the 
“World Medical Association Declaration of Helsinki” (as amended in Tokyo, Venice, Hong Kong, South 
Africa and Scotland and Note of Clarification Washington, 2002). 
 
The study must fully adhere to the principles outlined in “Guideline for Good Clinical Practice” 
International Committee on Harmonization (ICH) Tripartite Guideline (January 1997) and to 
ISO14155:2011 requirements. The investigator will additionally ensure that the basic principles of “Good 
Clinical Practices” as outlined in the current version of FDA 21 Code of Federal Regulations (CFR) 
Subchapter D, Part 312, “Responsibilities of Sponsors and Investigators”, Part 50, “Protection of Human 
Subjects” and Part 56, “Institutional Review Boards” are adhered to. 
14 IRB REVIEW 
 
The protocol and any accompanying material provided to the subject will be submitted by the 
investigator to an IRB committee.  Approval from the IRB must be obtained before starting the study, and 
should be documented in a letter to the investigator specifying the date on which the committee met and 
granted approval. 
 
Any modifications made to the protocol after receipt of the IRB or EC approval must also be 
submitted by the investigator to the board in accordance with the local procedures.  
Copies of all IRB correspondence with the investigator shall be provided to SinuSys Corporation. 
 
 
15 INFORMED CONSENT 
 
Voluntary informed consent will be obtained from all subjects, or the legally authorized 
representative of the subject participating in this study, in accordance with FDA regulations.  The 
subject’s informed consent must be obtained in writing prior to performance of any study-specific 
activity.  The informed consent form used to consent the subject must be approved by the reviewing IRB.   
The original signed consent form shall be maintained in the subject’s study file.  

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All subjects must be consented utilizing the most current approved version of the informed consent 
form, and re-consented if required by the IRB for any protocol amendments.  
 
The principles of informed consent must be followed to be in compliance with health authorities’ 
regulations for the conduct and monitoring of clinical investigations. 
16 SUBJECT CONFIDENTIALITY 
 
A report of the results of this study may be published or sent to the appropriate health authorities in 
any country in which the treatment product may ultimately be marketed, but the subject's name will not 
be disclosed in these documents. The subject’s name may be disclosed to, SinuSys Corp, the governing 
health authorities or the Food and Drug Administration (FDA), if they inspect the study records.  
Appropriate precautions will be taken to maintain confidentiality of medical records and personal 
information. 
Written authorization is to be obtained from each subject prior to enrollment into the study, and/or from 
the subject’s legally authorized representative in accordance with the applicable privacy requirements 
(e.g., the Health Insurance Portability and Accountability Act of 1996 Standards for Privacy of 
Individually Identifiable Health Information [“HIPAA”]) and any other state privacy requirements, as 
required by the study site.  
17 STUDY DOCUMENTATION, CRF’S AND RECORD KEEPING 
17.1 Investigator Files/Retention of Documents 
          Principal investigator shall maintain clinical investigation documents, including study related 
correspondence, subject records, consent forms, subject privacy documentation, records of the 
distribution and use of device, and copies of case report forms as required by the local or other applicable 
regulatory requirements. They shall take measures to prevent accidental or premature destruction of these 
documents. The principal investigator may transfer custody of records to another person/party and 
document the transfer at the investigation site or to provide these to SinuSys Corporation. 
18 STUDY MATERIALS ACCOUNTABILITY  
         Study materials accountability, reconciliation and record maintenance are responsibilities that must be 
performed in accordance with all applicable regulatory requirements. SinuSys will provide requested 
materials accountability records for this study for use by the investigative sites.  The recipient will 
acknowledge receipt of all study material shipments, indicating content and condition.  Damaged supplies 
will be replaced.      
      Accurate records of all study materials received, used to treat subjects, returned to the SinuSys, or 
designee, or destroyed at the study site, shall be maintained by the Investigator.  
      The investigator will not supply the study treatment materials to a third party, nor will he/she allow 
administration of the study material, other than as directed by this protocol to subjects properly enrolled 
into the study.  
 
The SinuSys Restora Spacer material will be stored appropriately at the study site until the end of the 
study.  All unused inventory will be stored for accountability and return.  All used spacers will be retained 

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and stored in a designated closed vial.  Storage and shipping procedures to return used and unused 
inventory will be provided by SinuSys. 
 
If the spacer material does not perform as intended, the study site will return the device to SinuSys 
and will document the performance issue. 
19 QUALITY CONTROL AND ASSURANCE 
 
Case Report Forms (CRFs) for this study will be designed and provided by the investigator.    A 
complete audit trail of changes to the data will be maintained and available upon request. 
 
 
 

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20 REFERENCES  
1. Bednarski KA, Kuhn FA. Stents and drug-eluting stents. Otolaryngologic clinics of North 
America 2009; 42:857-866, x. 
2. Miller RS, Steward DL, Tami TAet al. The clinical effects of hyaluronic acid ester nasal 
dressing (Merogel) on intranasal wound healing after functional endoscopic sinus surgery. 
Otolaryngology--head and neck surgery : official journal of American Academy of 
Otolaryngology-Head and Neck Surgery 2003; 128:862-869. 
3. Saafan ME, Ragab SM, Albirmawy OA, Elsherif HS. Powered versus conventional endoscopic 
sinus surgery instruments in management of sinonasal polyposis. European archives of oto-rhino-
laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies 
(EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck 
Surgery 2013; 270:149-155. 
4. Catalano PJ, Roffman EJ. Evaluation of middle meatal stenting after minimally invasive sinus 
techniques (MIST). Otolaryngology--head and neck surgery : official journal of American 
Academy of Otolaryngology-Head and Neck Surgery 2003; 128:875-881. 
5. Morissen M. Postoperative care following endoscopic sinus surgery. Rhinology 2004; 42:114-
120. 
6. Lee JY, Lee SW. Preventing lateral synechia formation after endoscopic sinus surgery with a 
silastic sheet. Archives of otolaryngology--head & neck surgery 2007; 133:776-779. 
7. Baguley CJ, Stow NW, Weitzel EK, Douglas RG. Silastic splints reduce middle meatal 
adhesions after endoscopic sinus surgery. American journal of rhinology & allergy 2012; 26:414-
417. 
8. Lee JM, Grewal A. Middle meatal spacers for the prevention of synechiae following 
endoscopic sinus surgery: a systematic review and meta-analysis of randomized controlled trials. 
International forum of allergy & rhinology 2012; 2:477-486. 
9. Maccabee MS, Trune DR, Hwang PH. Effects of topically applied biomaterials on paranasal 
sinus mucosal healing. American journal of rhinology 2003; 17:203-207. 
10. More Y, Willen S, Catalano P. Management of early nasal polyposis using a steroid-
impregnated nasal dressing  Int Forum Allergy Rhinol. 2011 Sep-Oct;1(5):401-4. 
11. Joshi RR, Nepal S et al  Merocel and Neosporin impregnated ribbon gauze pack in nasal 
surgery Health Renaissance 2012 (10): 30-34 
12. Marple BF, Smith TL, Han JKet al. Advance II: a prospective, randomized study assessing 
safety and efficacy of bioabsorbable steroid-releasing sinus implants. Otolaryngology--head and 
neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 
2012; 146:1004-1011. 

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13. Zhao X, Grewal A, Briel M, Lee JM. A systematic review of nonabsorbable, absorbable, and 
steroid-impregnated spacers following endoscopic sinus surgery. International forum of allergy & 
rhinology 2013; 3:896-904. 
14. Jorrisen C and Batchert C Effects of corticosteroids on wound healing after endoscopic sinus 
surgery Rhinology 47, 280-286, 2009 
15. Côté DW, Wright ED. Triamcinolone-impregnated nasal dressing following endoscopic sinus 
surgery: a randomized, double-blind, placebo-controlled study.  Laryngoscope. 2010 
Jun;120(6):1269-73. doi: 10.1002/lary.20905. 
 
 
 

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21 APPENDIX A 
SCHEDULE OF EVENTS 
Assessment 
Screening/ 
Enrolment 
 
Treatment 
 
Spacer Removal 
6+2 days 
Follow up 
5± 1 weeks 
Follow up 
13±2 weeks 
Informed Consent 
X 
 
 
 
 
Eligibility Criteria 
X 
X* 
 
 
 
Demographics 
X 
 
 
 
 
Pregnancy Assessment 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
CT Scan 
X 
 
 
 
 
Nasal Endoscopy 
X 
X 
X 
X 
X 
Endoscopic Videos 
Acquisition/LK score 
 
X 
X 
 
X 
X 
ESS procedure and spacer 
placement 
 
X 
 
 
 
Adverse Events/UADE 
 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
SNOT-22 
X 
 
 
 
X 
Frequency of events** 
 
 
 
X 
 
IOP (Intra-Ocular 
Pressure) 
X 
 
 
X 
X 
*If treatment performed on a different day than the Screening/enrollment visit 
** Data collection for frequency of post op interventions, oral steroid use and turbinate position