Spirox Latera™ Implant Support of Lateral Nasal Wall Cartilage (LATERAL-OR) Study
Phase: NA
Conditions: Nasal Obstruction
Sponsor: Spirox, Inc.



SPI-CP-301 LATERAL-OR Study Protocol  
Table of Contents 
 
 
LIST OF ABBREVIATIONS ............................................................................................................... i 
STATEMENT OF COMPLIANCE ...................................................................................................... ii 
PROTOCOL SUMMARY ................................................................................................................ iv 
SCHEMATIC OF STUDY DESIGN ..................................................................................................... v 
CLINICIAL PROTOCOL ................................................................................................................... 1 
1. 
KEY ROLES ..................................................................................................................................... 1 
2. 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE .................................. 3 
2.1. 
BACKGROUND INFORMATION ................................................................................................... 3 
2.2. 
PRIOR INVESTIGATIONS ............................................................................................................. 3 
2.3. 
POTENTIAL RISKS AND BENEFITS ................................................................................................ 4 
2.3.1. 
NON-SIGNIFICANT RISK RATIONALE ............................................................................................. 4 
2.3.2. 
KNOWN POTENTIAL RISKS ............................................................................................................ 5 
2.3.3. 
KNOWN POTENTIAL BENEFITS ...................................................................................................... 6 
3. 
OBJECTIVES AND PURPOSE ............................................................................................................ 6 
4. 
STUDY DESIGN AND ENDPOINTS .................................................................................................... 7 
4.1. 
DESCRIPTION OF THE STUDY DESIGN .......................................................................................... 7 
4.2. 
STUDY ENDPOINTS .................................................................................................................... 7 
4.2.1. 
PRIMARY ENDPOINTS ................................................................................................................... 7 
4.2.2. 
SECONDARY ENDPOINTS .............................................................................................................. 7 
4.2.3. 
EXPLORATORY ENDPOINTS ........................................................................................................... 7 
5. 
STUDY ENROLLMENT AND WITHDRAWAL ...................................................................................... 8 
5.1. 
PARTICIPANT INCLUSION CRITERIA ............................................................................................ 8 
5.2. 
PARTICIPANT EXCLUSION CRITERIA ............................................................................................ 8 
5.3. 
STRATEGIES FOR RECRUITMENT AND RETENTION ....................................................................... 9 
5.4. 
PARTICIPANT WITHDRAWAL OR TERMINATION.......................................................................... 9 
5.5. 
PREMATURE TERMINATION OR SUSPENSION OF STUDY ........................................................... 10 
6. 
STUDY DEVICE ............................................................................................................................. 10 
6.1. 
STUDY DEVICE ACQUISITION .................................................................................................... 10 
6.2. 
STUDY DEVICE DESCRIPTION AND INDICATIONS FOR USE ......................................................... 11 
6.3. 
STUDY DEVICE STORAGE AND STABILITY .................................................................................. 11 
6.4. 
STUDY DEVICE PREPARATION AND IMPLANTATION .................................................................. 12 
6.5. 
STUDY DEVICE ACCOUNTABILITY PROCEDURES ........................................................................ 12 
7. 
STUDY PROCEDURES AND SCHEDULE ........................................................................................... 12 
7.1. 
STUDY VISIT SPECIFIC PROCEDURES ......................................................................................... 12 
7.1.1. 
Subject Screening and Enrollment Visit (Visit 1) ........................................................................ 12 
7.1.2. 
Baseline Evaluation Visit (Visit 2) ................................................................................................ 12 
7.1.3. 
Treatment Visit (Visit 3) .............................................................................................................. 13 
7.1.4. 
Follow-Up Evaluation Visits (Visit 4-7) ........................................................................................ 14 
7.2. 
STUDY EVALUATIONS METHODS .............................................................................................. 15 
7.2.1. 
Nasal Obstruction Symptom Evaluation (NOSE) Scale ............................................................... 15 
7.2.2. 
NAO Breathing Assessment ........................................................................................................ 16 
7.2.3. 
Baseline Health Economics Questionnaire ................................................................................. 16 

SPI-CP-301 LATERAL-OR Study Protocol  
7.2.4. 
Post Procedure Health Economics Questionnaire ...................................................................... 16 
7.2.5. 
Demographics & Nasal Medical History ..................................................................................... 16 
7.2.6. 
Baseline Nasal Exam ................................................................................................................... 17 
7.2.7. 
Post Procedure Nasal Exam ........................................................................................................ 17 
7.2.8. 
Modified Cottle Maneuver ......................................................................................................... 17 
7.2.9. 
Lateral Wall Motion Video .......................................................................................................... 17 
7.2.10. 
Photography - Cosmetic ............................................................................................................. 18 
7.2.11. 
Photography – 3D ....................................................................................................................... 18 
7.2.12. 
Assessment of Turbinate Hypertrophy Contribution to NAO .................................................... 18 
7.2.13. 
Subject Satisfaction Questionnaire............................................................................................. 19 
7.2.14. 
Discretionary Imaging ................................................................................................................. 19 
7.2.15. 
Latera™ Patient Experience and Testimonials ............................................................................ 19 
7.3. 
LOST TO FOLLOW-UP ............................................................................................................... 19 
7.4. 
STANDARD OF CARE STUDY PROCEDURE .................................................................................. 20 
7.5. 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES ............................................ 20 
7.6. 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES ................................................. 20 
7.7. 
STUDY SCHEDULE OF EVENTS TABLE ......................................................................................... 21 
7.8. 
EARLY TERMINATION VISIT ...................................................................................................... 22 
7.9. 
UNSCHEDULED VISIT ........................................................................ Error! Bookmark not defined. 
8. 
ASSESSMENT OF SAFETY .............................................................................................................. 22 
8.1. 
SPECIFICATION OF SAFETY PARAMETERS .................................................................................. 22 
8.1.1. 
DEFINITION OF ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) ......................... 22 
8.1.2. 
DEFINITION OF ADVERSE DEVICE EFFECT (ADE) AND SERIOUS ADVERSE DEVICE EFFECT (SADE)
 
23 
8.1.3. 
DEFINITION OF UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) ........................................... 23 
8.2. 
CLASSIFICATION OF AN ADVERSE EVENT .................................................................................. 23 
8.2.1. 
SEVERITY OF EVENT .................................................................................................................... 23 
8.2.2. 
RELATIONSHIP TO STUDY DEVICE/PROCEDURES ....................................................................... 23 
8.2.3. 
EXPECTEDNESS............................................................................................................................ 24 
8.3. 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP .............................. 24 
8.4. 
REPORTING PROCEDURES ........................................................................................................ 25 
8.4.1. 
ADVERSE EVENT REPORTING ...................................................................................................... 25 
8.4.2. 
SERIOUS ADVERSE EVENT REPORTING ....................................................................................... 25 
8.4.3. 
UNANTICIPATED PROBLEM REPORTING..................................................................................... 25 
8.5. 
STUDY HALTING RULES ............................................................................................................ 25 
8.6. 
SAFETY OVERSIGHT .................................................................................................................. 25 
9. 
CLINICAL MONTIORING ............................................................................................................... 26 
10. 
STATISTICAL CONSIDERATIONS ................................................................................................ 26 
10.1. 
STATISTICAL AND ANALYTICAL PLANS ................................................................................... 26 
10.2. 
STATISTICAL HYPOTHESES .................................................................................................... 26 
10.3. 
ANALYSES DATASETS............................................................................................................ 26 
10.4. 
DESCRIPTION OF STATISTICAL METHODS .............................................................................. 27 
10.4.1. 
GENERAL APPROACH .................................................................................................................. 27 
10.4.2. 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) .................................................................. 27 
10.4.3. 
ANALYSIS OF THE SECONDARY ENDPOINT(S) ............................................................................. 27 
10.4.4. 
SAFETY ANALYSES ....................................................................................................................... 28 
10.4.5. 
ADHERENCE AND RETENTION ANALYSES ................................................................................... 28 
10.4.6. 
BASELINE DESCRIPTIVE STATISTICS ............................................................................................ 29 
10.4.7. 
PLANNED INTERIM ANALYSES .................................................................................................... 29 

SPI-CP-301 LATERAL-OR Study Protocol  
10.4.7.1. 
SAFETY REVIEW ....................................................................................................................... 29 
10.4.7.2. 
EFFICACY REVIEW ................................................................................................................... 29 
10.4.8. 
ADDITIONAL SUB-GROUP ANALYSES .......................................................................................... 29 
10.4.9. 
MULTIPLE COMPARISON/MULTIPLICITY .................................................................................... 29 
10.4.10. 
TABULATION OF INDIVIDUAL RESPONSE DATA ...................................................................... 29 
10.4.11. 
EXPLORATORY ANALYSES ....................................................................................................... 29 
10.5. 
SAMPLE SIZE ........................................................................................................................ 30 
10.6. 
MEASURES TO MINIMIZE BIAS .............................................................................................. 30 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ........................................ 30 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL ......................................................................... 31 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................. 31 
13.1. 
ETHICAL STANDARD ............................................................................................................. 31 
13.2. 
INSTITUTIONAL REVIEW BOARD ........................................................................................... 31 
13.3. 
INFORMED CONSENT PROCESS ............................................................................................. 31 
13.3.1. 
CONSENT AND OTHER INFORMATIONAL DOCUMENTATION PROVIDED TO PARTICIPANTS ..... 31 
13.3.2. 
CONSENT PROCEDURES AND DOCUMENTATION ...................................................................... 32 
13.4. 
PARTICIPANT AND DATA CONFIDENTIALITY .......................................................................... 32 
13.5. 
COMPENSATION FOR INJURY ............................................................................................... 33 
14. 
DATA HANDLING AND RECORD KEEPING .................................................................................. 33 
14.1. 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES ................................................... 33 
14.2. 
STUDY RECORDS RETENTION ................................................................................................ 33 
14.3. 
PROTOCOL DEVIATIONS ....................................................................................................... 33 
14.4. 
PUBLICATION AND DATA SHARING POLICY ........................................................................... 34 
15. 
STUDY ADMINISTRATION ......................................................................................................... 34 
15.1. 
STUDY LEADERSHIP .............................................................................................................. 34 
16. 
CONFLICT OF INTEREST POLICY ................................................................................................. 34 
17. 
LITERATURE REFERENCES ......................................................................................................... 34 
APPENDIX I – PROTOCOL REVISION HISTORY ....................................................................................... 36 
APPENDIX II – NONSIGNIFICANT RISK RATIONALE................................................................................ 37 
  
 
 
 
 
 
 
 

i 
Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
September 7, 2017 
 
SPI-CP-301 LATERAL-OR Study Protocol 
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
ASC 
Ambulatory Surgery Center 
CFR 
Code of Federal Regulations 
CMP 
Clinical Monitoring Plan 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
eCRF 
Electronic Case Report Form 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Conference on Harmonisation 
ICH E6 
International Conference on Harmonisation Guidance for Industry, Good Clinical Practice: 
Consolidated Guidance 
ICMJE 
International Committee of Medical Journal Editors 
IFU 
Instructions for Use 
IRB 
Investigational Review Board 
ISO 
International Organization for Standardization 
LWI 
Lateral Wall Insufficiency  
MAC 
Monitored Anesthesia Care 
NAO 
Nasal Airway Obstruction 
NSR 
Non-significant Risk 
NOSE 
Nasal Obstruction Symptom Evaluation  
NVC 
Nasal Valve Collapse 
OHRP 
Office for Human Research Protections 
PRO 
Patient Reported Outcome 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
QOL 
Quality of Life 
QSR 
21CFR Part 820, Quality System Regulation 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SAP 
Statistical Analysis Plan 
SOP 
Standard Operating Procedure 
UADE 
Unanticipated Adverse Device Effect 
UP 
Unanticipated Problem 
US 
United States 
VAS 
Visual Analog Scales 

ii 
Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
September 7, 2017 
 
SPI-CP-301 LATERAL-OR Study Protocol 
STATEMENT OF COMPLIANCE 
 
I have received and reviewed this protocol.  The trial will be carried out in accordance with this protocol 
and Good Clinical Practice (GCP) as required by the following: 
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, and 21 CFR Part 56, and 21 CFR Part 812.2(b) 
• 
International Conference on Harmonisation (ICH) Good Clinical Practice E6 
• 
ISO 14155:2011 Clinical investigation of medical devices for human subjects - GCP 
 
All key personnel (all individuals responsible in the conduct of this trial) have completed Human 
Subjects Protection Training. 
 
I agree to ensure that all staff members involved in the conduct of this study are informed about their 
obligations in meeting the above commitments. 
 
 
_____________________________________________________________________ 
Investigator’s Printed/Typed Name 
 
 
 
_____________________________________________________________________ 
Investigator’s Signature 
 
 
 
Date 
 

Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
September 7, 2017 
 
iv 
PROTOCOL SUMMARY 
 
Title: 
Spirox LateraTM Implant support of lateral nasal wall cartilage (LATERAL-OR) study 
Design: 
A prospective, multi-center, non-randomized, single arm, controlled study 
Objectives: 
To obtain outcomes data in subjects with severe to extreme class NOSE scores 
undergoing placement of the Spirox Latera Implant with or without concurrent 
septoplasty and/or turbinate reduction procedures in an operating room setting. 
Eligibility Criteria 
Reference Sections 5.1 and 5.2 below. 
Primary Endpoints: 
Primary Efficacy Endpoint: Proportion of treatment responders at 6 months post 
procedure. 
Responder is defined as subject that has at least one (1) NOSE class improvement or 
at least 20% NOSE score reduction  
Primary Safety Endpoint: Nasal procedure and Latera™ device-related adverse events 
through 6 months 
Secondary Endpoints: 
1. Proportion of treatment responders at 1, 3, 12, 18 and 24 months post 
procedure. 
2. Change in nasal airway obstruction from baseline to 1,3, 6, 12, 18 and 24 months 
as reported by subjects on the VAS scale. 
3. Subject satisfaction questionnaire at 6 months. 
4. Procedure and device-related adverse events though 24 months. 
Exploratory endpoints: 
Reference Section 4.2.3 below. 
Population: 
Up to 170 subjects will be enrolled  
Number of Sites: 
Approximately 25 sites in the U.S.  
Description of Device: 
The Latera™ Absorbable Nasal Implant and Delivery Device includes an absorbable 
implant designed to provide internal support of the upper and lower lateral nasal 
cartilages.  The Implant absorbs over a period of approximately 18 months.  The 
absorbable Implant is comprised of a 70:30 blend of poly(L-lactide) and poly(D-
lactide).  The Implant is introduced through a trans-mucosal insertion technique using 
a delivery device.  The Implant consists of a ribbed cylindrical structure which 
employs a forked end to facilitate anchoring within the target tissue.  The geometry 
of the forked end is flexible, and collapses to fit within the 16-gauge cannula portion 
of the delivery tool.  
Study Duration: 
Approximately 36 months from when enrollment begins to completion of data 
analyses. 
Participant Duration: 
Enrolled subjects will be followed for 24 months post-procedure 
Regulatory Status: 
This study is a post-market evaluation of a 510(k) cleared, non-significant risk, 
medical device in commercial distribution, used according to FDA cleared 
indications for use. 
 

Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
September 7, 2017 
 
v 
SCHEMATIC OF STUDY DESIGN 
 
 
 
 
Visit 1 
Time Point 
Screen potential subjects by inclusion and exclusion criteria; Obtain informed 
consent. Refer to Section 7.7, Schedule of Events Table. 
Visit 2 
Time Point 
Perform baseline assessments.  
Refer to Section 7.7, Schedule of Events Table. 
Visit 3 
Time Point 
Treatment and safety assessments.  
Refer to Section 7.7, Schedule of Events Table. 
Visit 4-9 
Time Points 
Follow-up assessments and study endpoints and safety assessments.  
Refer to Section 7.7, Schedule of Events Table. 
Visit 9 
Time Point 
Study exit.  
Refer to Section 7.7, Schedule of Events Table. 

Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
September 7, 2017 
 
1 
CLINICIAL PROTOCOL 
 
1. 
KEY ROLES 
 
The following list of persons, companies, and/or groups serve in key roles in the conduct or oversight of the 
trial: 
 
Sponsor Contacts 
 
Sponsor Contact 
Elisa Hebb 
V.P., Clinical and Regulatory Affairs 
Spirox Inc. 
595 Penobscot Drive 
Redwood City, CA 94063 
(510) 604-7372 
ehebb@spiroxmed.com 
Medical Monitor 
Donald Gonzales, M.D. 
Chief Medical Officer 
Spirox, Inc. 
 
595 Penobscot Drive 
Redwood City, CA  94063 
(650) 503-3329 
dgonzales@spiroxmed.com 
 
 
Statistics and Database Management 
Vaishali Suraj 
Director, Biometrics 
Spirox Inc. 
3475 Edison Way, Suite O 
Menlo Park, CA 94025 
(408) 891-3321 
vsuraj@spiroxmed.com  
 
 
Consulting Statistician  
April Slee  
New Arch Consulting 
8610 41st SW 
Seattle, WA 98136 
 
Principal Investigators 
 
Douglas Sidle, MD 
Assistance Professor, Otolaryngology – Head & 
Neck Surgery 
Northwestern University 
Feinberg School of Medicine 
NMH/Galter Room 15-200 
675 N. Saint Clair 
Chicago, IL  60611 
(312) 695-8182dsidle@nmff.org 
 
Pablo Stolovitzky, MD 
ENT of Georgia 
5673 Peachtree Dunwoody Rd, Suite 150 
Atlanta, GA 30342 
(404) 297-4230 
stol@entofga.com 
Jeffrey Suh, MD 
Department of Head & Neck Surgery 
UCLA 
10833 Le Conte Avenue 
Los Angeles, CA  90095 
(310) 206-6688 
JeffSuh@mednet.ucla.edu 
 

Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
September 7, 2017 
 
2 
Independent Reviewers 
 
Endonasal Scale Scoring 
Sam Most, M.D., F.A.C.S. 
Stanford ENT 
801 Welch Rd, MC 5739 
Stanford, CA 94305 
(650) 736-3223 
smost@stanford.edu 
 
Cosmetic Photography Reviewer 
Grant Hamilton III, M.D. 
Mayo Clinic 
201 1st Ave SW 
Rochester, MN 55902 
(507) 284-3856 
granthamilton@mac.com 
 
 
EDC/Database Hosting 
 
MedNet Solutions Inc. 
110 Cheshire Ln. 
Minnetonka, MN 55305 
(763) 258-2735 
 
 
 
File Transfer Hosting 
 
BrickFTP.com 
Action Verb, LLC 
8605 Santa Monica Blvd #20898 
West Hollywood, CA 90069 
(800) 286-8372 
 
 
 
 
 

Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
September 7, 2017 
 
SPI-CP-301 LATERAL-OR Study Protocol 
3
2. 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
2.1. 
BACKGROUND INFORMATION 
Nasal airway obstruction can be caused by several independent or concomitant factors including septal 
deviation, enlarged turbinates and a weakened nasal lateral wall, leading to nasal valve collapse (NVC).  The 
nasal valve, first described in the early 20th century by Mink1, is a complex, three-dimensional, dynamically-
alternating structure that controls nasal airflow resistance.  A dysfunction of the nasal valve can lead to nasal 
obstruction with a significant drop in the quality of life for patients2.  As defined by the Hagen–Poiseuille law, 
the flow through a tube is proportional to the 4th power of the radius of the tube and inversely proportional 
to the pressure difference across the tube.  Although more complex models would be required to account 
for turbulence and other factors, it is clear that even a small decrease in the valve area can contribute to 
nasal obstruction. Common causes of NVC are prior rhinoplasty, aging, nasal trauma and congenital 
abnormalities that weaken the nasal cartilage, leading to a lateral wall insufficiency (LWI)3,4.   
 
Therapies to correct NVC include invasive surgical procedures and non-surgical solutions to temporarily 
dilate the nasal valve, such as Breathe Right® strips or nasal cones.  Surgical strategies that involve 
septoplasty5 or inferior turbinate reduction6 may alleviate impaired nasal breathing, but do not directly 
address the weakened lateral wall.  Procedures intended to stabilize the lateral wall include cartilaginous 
grafts typically harvested from the nasal septum7, ear8 or rib cartilage9.  These grafts can be placed as lateral 
crural strut grafts10, alar batten grafts11 or butterfly grafts12.  Implants made from non-absorbable alloplastic 
materials have also been used for treatment of NVC including expanded polytetrafluoroethylene13 and high-
density porous polyethylene14.  These materials have not gained wide utilization as they require invasive 
surgical procedures and are associated with increased risks of infection, extrusion, and the potential need for 
revision procedures.  
 
Surgery to strengthen the lateral wall has been shown to significantly improve the quality of life for subjects 
suffering from nasal airway obstruction15, however current procedures are generally invasive and have the 
potential to permanently alter the patient’s appearance16.  This study utilizes a minimally invasive technique 
to address NVC by supporting the nasal lateral wall cartilage with an absorbable implant utilized. 
 
Spirox has developed the Latera Absorbable Nasal Implant and Delivery Device, to enable a less invasive 
alternative to current surgical approaches used to support weak lateral wall cartilage.  This device has been 
cleared by the U.S. FDA via 510(k) submissions and is currently in commercial distribution.  The device will be 
used according to the cleared indications for use in this study.  This non-significant risk, post-market study 
seeks to obtain outcomes data in subjects with severe to extreme17 severity class NOSE scores (≥ 55), 
undergoing placement of Spirox Latera Absorbable Nasal Implant with or without concurrent septoplasty 
and/or turbinate reduction procedures in an operating room setting. 
 
2.2. 
PRIOR INVESTIGATIONS 
A prior study of this device was performed in the setting of an EC approved protocol in Germany.  The study 
was conducted at three institutions under the oversight of Co-Principal Investigators, Professor Alexander 
Berghaus, MD and Marion San Nicolo, MD in Munchen, Germany.  This prior first in man investigation 
evaluated the safety and performance of the Spirox device and its ability to support upper and lower lateral 
cartilage in subjects with nasal valve collapse as primary contributor to nasal airway obstruction (NAO) under 
general or local anesthesia.  A brief summary of this prior investigation follows. 
 

Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
SPI-CP-301 
Version 2.0 
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SPI-CP-301 LATERAL-OR Study Protocol 
4
Fourteen (14) cases were performed in an operating suite under general anesthesia and sixteen (16) cases 
were performed in a clinic-based setting under local anesthesia.  A total of fifty-six Implants were placed in 
thirty subjects.  Subjects with a Nasal Obstruction Symptom Evaluation (NOSE) scale score ≥ 55 and Nasal 
Valve Collapse as primary contributor to NAO were treated.  Follow-up visits occurred at week 1 and months 
1, 3, 6, 12 and 18 post procedure. These visits included documentation of medical history, physical exam, 
NOSE score and digital photography.  The NOSE scale is a validated as a Quality of Life (QOL) instrument18.  It 
uses a 20-point scale to capture severity of breathing symptoms, with higher scores indicating more severe 
symptoms than lower scores.  The results are converted to 100-point scale by multiplying the total score by 
five.   
 
There was a total of five (5) device-related adverse events reported in four (4) subjects.  These events 
included 1 case of hematoma, 1 case of inflammation, and 3 Implant retrievals.  All events resolved with no 
clinical sequelae. Investigators concluded that the 3 Implant retrievals were the result of suboptimal 
implantation methods or possible significant patient lateral wall manipulation during the first post-operative 
week and were not caused by adverse physiologic tissue rejection or infection.  The Implant placement 
procedure was revised during the course of the study to address suboptimal implantation techniques and no 
further retrieval events occurred.  
 
To date, all follow up visits through 18 months have been completed; 15 out of 30 subjects completed 18 
months of follow up.  Three subjects have had other nasal surgery procedures and consequently exited the 
study; two subjects after the 12 month visit and one subject after the 18 month visit. 
 
A longitudinal summary of NOSE score is provided in the table below and these results demonstrate 
significant improvements over baseline for all time points measured. 
 
  
  
Score 
Change from baseline 
% Change from baseline 
Visit 
N 
Mean (SD) 
Mean (SD) 
LS Mean (95% CI) 
p-value 
Mean (SD) 
LS Mean (95% CI) 
p-
value 
1 Week 
30 
24.2 (16.14) 
-52.5 (22.77) 
-52.7 (-58.83, -46.55) 
<.001 
-67.2 (21.34) 
-67.2 (-74.98, -59.51) 
<.001 
1 Month 
30 
27.0 (23.95) 
-49.7 (25.56) 
-49.9 (-58.79, -40.93) 
<.001 
-64.8 (29.09) 
-64.9 (-75.92, -53.86) 
<.001 
3 Months 
29 
28.4 (26.90) 
-48.4 (27.84) 
-47.9 (-57.85, -37.96) 
<.001 
-63.4 (34.45) 
-62.7 (-75.70, -49.66) 
<.001 
6 Months 
30 
33.3 (29.69) 
-43.3 (31.28) 
-43.5 (-54.61, -32.44) 
<.001 
-56.2 (37.85) 
-56.3 (-70.46, -42.07) 
<.001 
12 Months 
29 
35.2 (29.17) 
-40.9 (31.23) 
-39.7 (-51.22, -28.11) 
<.001 
-53.1 (40.64) 
-51.6 (-67.07, -36.12) 
<.001 
18 Months 
15 
38.0 (33.32) 
-41.7 (36.24) 
-40.7 (-55.01, -26.30) 
<.001 
-51.3 (41.76) 
-52.2 (-70.59, -33.87) 
<.001 
 
This first in man study demonstrated the safety and effectiveness of the absorbable Implant to provide 
lateral cartilage support in patients with NVC as primary contributor to NAO.  
 
2.3. 
POTENTIAL RISKS AND BENEFITS 
2.3.1. NON-SIGNIFICANT RISK RATIONALE 
This is a Non-Significant Risk (“NSR”), post-marketing study and will be conducted in accordance with the 
requirements prescribed in 21 CFR §812.2(b). Because it is a post-market evaluation of a 510(k) cleared 
medical device in commercial distribution, used according to FDA cleared indications for use, investigational 
device labeling described under §812.2(b) is not required. 
 

Spirox Latera™ implant support of lateral wall cartilage (LATERAL-OR) study 
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SPI-CP-301 LATERAL-OR Study Protocol 
5
This evaluation of the Spirox Latera™ Absorbable Nasal Implant and Delivery Device is considered a NSR 
device study for the following reasons: 
 
• 
While the device is an Implant, it does not present a potential for serious risk to the health, safety, or 
welfare of a subject; 
• 
The device is not purported or represented to be used for supporting or sustaining human life; 
• 
The device is not intended for a use of substantial importance in diagnosing, curing, mitigating, or 
treating disease or otherwise preventing impairment of human health; and, 
• 
The device does not otherwise present a potential for serious risk to the health, safety or welfare of 
the subject.  
 
See Appendix II for additional information supporting the rationale for a Non-Significant Risk determination. 
 
2.3.2. KNOWN POTENTIAL RISKS 
In patients with nasal airway obstruction, three factors may influence a decrease in the cross-sectional area 
of the nasal passage:  (1) deviated septum, (2) enlarged turbinates, and (3) collapsed lateral wall.  If all three 
etiologies are present, the surgeon would offer a treatment that would address all three.  Thus, the subjects 
may undergo Implant placement in conjunction with septoplasty and/or inferior turbinate reduction 
procedures.   
 
Both septoplasty and turbinectomy procedures are standards of care for the treatment of nasal airway 
obstruction.  In the US alone, there are at least 340,000 of these procedures completed each year.  The 
frequency of peri-operative adverse events is low, with an overall admittance rate of hospitalization of 
0.85%.  The most common reason for readmissions is hemorrhage19.   Possible risks and complications for 
each procedure are described below. 
 
Septoplasty procedure risks may include: 
• 
Infections 
• 
Nasal bleeding that may require surgical intervention or nasal packing 
• 
Numbness of the nose, cheeks, and upper lip 
• 
Bruising and swelling of the nose, eyelids, and upper lip 
• 
Scarring, septal perforations, nose shape change including “saddle nose” deformity and nostril 
asymmetry 
• 
A decreased sense of smell 
• 
General anesthesia effect 
• 
Pain and discomfort in the nose, particularly at the front 
• 
Continued nasal obstruction 
• 
Nasal crusting 
• 
Cerebrospinal fluid leak 
• 
Death 
 
The following complication rates have been reported after septoplasty20: 
• 
Infections – 3% 
• 
Hematomas – 2-7% 
• 
Septum perforations – 3-25% 
• 
Changes in nose shape -5-60% 
• 
Smelling disorders – less than 1% 

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Turbinate reduction procedure risks may include: 
• 
Mild-to-moderate edema with subsequent nasal obstruction and thick mucus formation  
• 
If mucosal erosion is present, the risk of postoperative bleeding and adherent crust formation 
increases  
• 
Scar tissue (synechiae) may form between the turbinate and the septum  
• 
Bleeding requiring further intervention 
• 
Empty nose syndrome 
 
The following complication rates have been reported after turbinate reduction: 
• 
Synechiae rates up to 36%20. 
 
Latera™ implant procedure risks may include: 
• 
Inflammatory foreign body reaction, foreign body sensation, pain or discomfort, infection, and 
extrusion 
• 
Excessive activity, trauma, or loading may lead to bending, fracture, loosening, and/or migration of 
the Implant 
• 
Implants placed near the skin surface may be palpable or cause skin irritation 
• 
Temporary hematoma from cannula insertion 
• 
Implant retrieval, defined as surgeon initiated removal of implant not associated with body rejection 
of implant 
• 
Unintended perforation of the skin 
 
Risks related to the Latera Implant will be mitigated throughout the course of the study by investigator 
training, study monitoring and follow up evaluations.  The training related to device placement will be 
provided to the investigators by the sponsor in a clinically relevant model prior to device use in clinic.  Only 
procedure-trained investigators that are authorized by the sponsor will be allowed to place the devices 
during the study.  In addition, prior to initiation of enrollment, procedure-trained investigators will have 
completed a number of commercial cases. 
 
Monitoring and follow up will ensure that adverse events are being reported in a timely manner and shared 
with the principal investigators and members of the research team.  Corrective action will be immediately 
taken if untoward trends are observed with a particular investigator. 
 
2.3.3. KNOWN POTENTIAL BENEFITS 
The LateraTM Absorbable Nasal Implant is indicated to support upper and lower lateral nasal cartilage.  The 
prior investigation described in Section 2.2, demonstrated that the device reduced nasal obstruction 
symptoms by 53.1 % at 12 months in patients with nasal valve collapse as primary contributor to NAO (no 
septal or turbinate treatment).  For subjects requiring lateral cartilage support that also have deviated 
septum and enlarged turbinates, it is expected that the Latera Implant may provide additional benefit to the 
subjects who are also undergoing concurrent septoplasty and/or turbinate procedures.  In addition, subjects 
may benefit from the additional clinical monitoring and follow-up evaluations required by this study 
protocol. 
 
3. 
OBJECTIVES AND PURPOSE 
The objective of the LATERAL-OR study is to obtain outcomes data in subjects with severe to extreme17 class 
NOSE scores undergoing placement of the Spirox Latera Implant with or without concurrent septoplasty 
and/or turbinate reduction procedures in an operating room setting. 

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4. 
STUDY DESIGN AND ENDPOINTS 
4.1. 
DESCRIPTION OF THE STUDY DESIGN 
This is a prospective, multi-center, non-randomized, single arm controlled study.  It is a post-market 
evaluation of a 510(k) cleared, non-significant risk, medical device in commercial distribution, used according 
to FDA cleared indications for use.  Each subject serves as his or her own control. 
 
4.2. 
STUDY ENDPOINTS 
4.2.1. PRIMARY ENDPOINTS 
Primary Efficacy Endpoint:  Proportion of treatment responders at 6 months post procedure. 
 
• 
Responder is defined as subject that has at least 1 NOSE class improvement or at least 20% NOSE 
score reduction  
 
Primary Safety Endpoint:  Nasal procedure and Latera device-related adverse events through 6 months. 
 
4.2.2. SECONDARY ENDPOINTS 
1. Proportion of treatment responders at 1, 3, 12, 18 and 24 months post procedure. 
2. Change in nasal airway obstruction from baseline to 1,3, 6,12, 18 and 24 months as reported by 
subjects on the VAS scale. 
3. Subject satisfaction questionnaire at 6 months. 
4. Procedure and device-related adverse events though 24 months. 
 
4.2.3. EXPLORATORY ENDPOINTS 
Exploratory endpoints for informational purposes only: 
 
1. Index procedure resource utilization: Anesthesia, procedure time and time to discharge. 
2. Follow up resource utilization: Nasal airway obstruction related return visits and medication 
utilization. 
3. Subject satisfaction questionnaire at 1, 3 and 12 months. 
4. Degree of nasal way obstruction as reported by subjects on the VAS scale at baseline with 
decongestant use. 
5. Endoscopic lateral wall insufficiency score per side21 at baseline and 6 months 
6. 3-D camera lateral wall motion assessment per side at baseline and 3, 6 and 12 months (at select 
sites). 
7. Cosmesis changes from baseline evaluated by Independent Photo Review 3 and 6 months (at select 
sites). 
8. Allergic rhinitis status at 1, 3, 6 and 12 months. 
9. Nasal geometry: length of nose, height and width of nose, skin thickness of lateral wall at baseline. 
10. Type of turbinate procedure. 
 
 
 

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5. 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1. 
PARTICIPANT INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following inclusion 
criteria: 
 
1. The subject has NOSE Score ≥55. 
2. The subject has dynamic lateral nasal wall insufficiency as confirmed by positive Modified Cottle 
Maneuver. 
3. The subject is ≥18 years of age. 
4. The subject is willing and able to provide informed consent and comply with the study protocol. 
5. The subject is seeking treatment for nasal airway obstruction due to Nasal Valve Collapse (NVC) and 
is willing to undergo nasal Implant procedure alone or with septoplasty and/or a turbinate reduction 
procedure in an operating room setting. 
6. The subject has appropriate nasal and facial anatomy to receive Latera Implant. 
7. The subject agrees to follow-up examinations through twelve (12) months post operatively. 
8. The subject has failed to benefit from appropriate maximal medical management [e.g., nasal steroids 
(at least 4 weeks); antihistamines; oral decongestants; nasal strips, stents, or cones]. Failure of 
maximal medical management may be from lack of effectiveness or inability of subject to tolerate. 
 
5.2. 
PARTICIPANT EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. The subject is having a concurrent Functional Endoscopic Sinus Surgery (FESS) or sinuplasty. 
2. The subject has had rhinoplasty within the past twelve (12) months. 
3. The subject is planning to have other concurrent rhinoplasty procedure.  
4. The subject is planning to have other rhinoplasty procedures or will use external dilators within 
twelve (12) months after the index procedure. 
5. The subject has had septoplasty and/or inferior turbinate reduction within the past six (6) months.  
6. The subject has, in the view of the clinician, inappropriate fixation on their nasal airway. 
7. The subject plans to have any surgical or non-surgical treatment of their nasal valve, other than the 
index procedure, within twelve (12) months of the study. 
8. The subject has a permanent implant or dilator in the nasal area.  
9. The subject has concomitant inflammatory or infectious skin conditions or unhealed wounds in the 
treatment area. 
10. The subject currently has active nasal vestibulitis. 
11. The subject has a history of nasal vasculitis. 
12. The subject is a chronic systemic steroid or recreational intra-nasal drug user.  
13. The subject has had a cancerous or pre-cancerous lesion and/or has had radiation exposure in the 
treatment area or chemotherapy.  
14. The subject has polyps or pathology other than septal deviation and/or turbinate hypertrophy 
and/or lateral wall insufficiency that would contribute to airway obstruction. 
15. The subject has a history of a significant bleeding disorder(s) that would prevent healing of the 
treatment area post procedure. 

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16. The subject has a known or suspected allergy to PLA or other absorbable materials. 
17. The subject has a significant systemic disease such as poorly controlled diabetes which, in the 
investigator’s opinion, could pre-dispose the subject to poor wound healing. 
18. The subject is currently using nasal oxygen or CPAP. 
19. The subject is not a candidate for procedures conducted under general anesthesia, managed 
anesthesia care (MAC) or conscious sedation. 
20. For female subjects, subject is known or suspected to be pregnant or is lactating. 
21. Any other presenting condition that in the medical opinion of the investigator would disqualify the 
subject.  
 
5.3. 
STRATEGIES FOR RECRUITMENT AND RETENTION 
A maximum of 170 subjects will be enrolled in the study to reach target of 150 subjects completing the 24 
Month follow-up post-procedure.  It is anticipated that this enrollment will take place in the initial 8 months 
of the study after study start-up.  Subjects will be enrolled at approximately 25 individual sites within the 
United States. 
 
Subjects will be recruited from sites’ existing patient populations that are seeking treatment for nasal airway 
obstruction including nasal valve collapse.  Anatomical considerations may impact the race distribution (e.g. 
some races may be less prone to lateral wall collapse), but the intention is to enroll all eligible subjects.  
Based on an earlier study with the device, both genders are expected to be well represented in the study.  
 
Study brochures containing information on study participation and the Implant may be provided to the sites, 
as well as posters that may be displayed either as hard copies or electronically on computer monitors in the 
office. 
 
The following tools will be utilized to encourage subjects’ compliance to the study visit schedule: 
 
• 
Subjects will receive a stipend for their time and to cover travel costs as follows:  Subjects who 
complete the study are eligible for a total stipend of up to $700 to be paid over a two year period.  
Upon completion of the Baseline, 1 Month, 3 Month, 6 Month,12 Month, 18 Month and 24 Month 
visits, subjects will receive a $100 prepaid debit card at each visit or follow up. The 18 Month and 24 
Month follow up evaluations will be conducted in one of the following manners:  office visit, 
telephone interview, or  completion of form by subject and mailed to office for data entry, 
depending on subject availability. 
• 
Additionally, subjects will be contacted by phone, and where available automated texting and email, 
for both reminders to schedule or confirm upcoming study visits and as reminders for visits that have 
already been scheduled. 
 
5.4. 
PARTICIPANT WITHDRAWAL OR TERMINATION 
Participants are free to withdraw from participation in the study at any time upon request.  Investigators 
may withdraw a subject from the study as deemed appropriate per safety measures and/or if the subject 
develops a medical condition that prohibits further study participation.   
 
In the event of an early subject termination, the clinical site will document Adverse Events, Concomitant 
Medications changes, as appropriate, and all available data in the eCRFs.  The clinical site will also complete 
the Study Exit eCRF. 

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5.5. 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
The study enrollment may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to the investigator and regulatory authorities.  If the study 
is prematurely terminated or suspended, the site PI will promptly inform the IRB(s) and will provide the 
reason(s) for the termination or suspension. 
 
Both the sponsor and the investigator reserve the right to terminate the study at any time. In terminating 
the study, the sponsor and the investigator will assure that adequate consideration is given to the protection 
of the Subjects interests. 
 
If the sponsor, investigator, study monitor, or appropriate regulatory officials discover any conditions arising 
during the study that indicate that the study enrollment should be suspended or that the study site should 
be terminated, this action may be taken after appropriate consultation among the sponsor, investigator, and 
study monitor.  Conditions that may warrant enrollment suspension or termination of the study site or of the 
study itself, may include, but are not limited to, the following:  
 
• 
The discovery of an unexpected, serious, or unacceptable risk to the subjects enrolled in the study; 
• 
A decision on the part of the sponsor to discontinue the study; 
• 
A decision on the part of the sponsor to suspend or discontinue evaluation of the device; 
• 
A request from a regulatory authority; 
• 
Failure of the investigator to enroll subjects into the study at an acceptable rate; 
• 
Failure of the investigator to comply with pertinent regulations of appropriate regulatory authorities; 
• 
Submission of knowingly false information from the research facility to the sponsor, study monitor, 
or appropriate regulatory authority; 
• 
Insufficient adherence to protocol requirements. 
• 
Determination that it is unlikely that the study null hypothesis can be rejected 
 
In the event of enrollment suspension, the study may resume once concerns about safety, protocol 
compliance, or data quality are addressed to the satisfaction of the sponsor, IRB and/or FDA. 
 
Subjects that have been enrolled and have undergone the index procedure at the time of study enrollment 
suspension will only be followed per the study schedule through the 24-Month close-out visit in the event 
the study is re-started.  Subjects that have been consented, but not yet undergone index procedure, will be 
delayed until a determination to restart enrollment has been made.  These latter subjects will be re-
consented if the enrollment suspension lasts longer than thirty (30) days. 
 
6. 
STUDY DEVICE 
6.1. 
STUDY DEVICE ACQUISITION 
The Latera™ System (Absorbable Nasal Implant and Delivery Device) is a commercially available device that 
has received FDA clearance (K161191).  The device will be used under this study protocol in accordance with 
the cleared indications for use and instructions for use.  The devices used in this study will be purchased 
through standard channels for obtaining commercial product from Spirox, Inc.  
 
 
 

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6.2. 
STUDY DEVICE DESCRIPTION AND INDICATIONS FOR USE 
The Latera Absorbable Nasal Implant is indicated for supporting nasal upper and lower lateral cartilage.  The 
absorbable nasal Implant is comprised of a 70:30 blend of poly(L-lactide) and poly(D-lactide). The Implant is 
predominantly cylindrical in shape with a diameter of 1 mm and an overall length of 24 mm with a forked 
distal end for anchoring and features on the proximal end for increased flexibility. The copolymer is absorbed 
by the body over a period of approximately 18 months22.  The Implant is provided in a plastic tray with a 
sliding lid.  The Implant and plastic tray are depicted in Figure 1 below. 
 
 
 
 
Figure 1: Latera Absorbable Nasal Implant and Packaging 
 
The Delivery Device is a single use device composed of a handle body, deployment plunger and pushrod, and 
a 16-gauge delivery cannula with a depth marker and protective cover.  The handle includes an Implant 
loading port which enables the loading of the Implant. The handle uses an internal transition between the 
loading position and the cannula to collapse the Implant forks within the cannula inner lumen and prepare 
the Implant for deployment.  The Implant Positioning Guide is packaged with the Delivery Device to aid the 
physician in preparing for the procedure and identifying the target Implant location. The Delivery Device and 
the Implant Positioning Guide are shown in Figure 2 below. 
Figure 2: Delivery Device and Implant Positioning Guide 
 
6.3. 
STUDY DEVICE STORAGE AND STABILITY 
Follow Instructions for Use.  The Implants are shipped in insulated containers containing frozen ice packs to 
protect the product from reaching high temperature. The Implants must be stored in a cool, dry location at 
Implant Loading Port 
Deployment Plunger 
and Pushrod 
Fork Orientation 
Features 
Distal and Proximal 
Marking Holes 
Delivery Cannula with 
Depth Marker  
(Cover removed) 
Implant Positioning Guide 

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or below 30°C.  The delivery tools are shipped in cardboard boxes and are not subject to special shipping, 
storage or temperature requirements. 
 
6.4. 
STUDY DEVICE PREPARATION AND IMPLANTATION 
Instructions regarding the device preparation are provided in the Instructions for Use (IFU) (see Addendum A 
Latera IFU). 
 
6.5. 
STUDY DEVICE ACCOUNTABILITY PROCEDURES 
The investigator will maintain records for all devices received and used. The lot number of each unit used will 
be tracked on the subject’s eCRF. 
 
7. 
STUDY PROCEDURES AND SCHEDULE 
7.1. 
STUDY VISIT SPECIFIC PROCEDURES 
7.1.1. Subject Screening and Enrollment Visit (Visit 1) 
All subjects seeking treatment for nasal obstruction will be screened for eligibility, according to 
inclusion/exclusion.  A member of the research team will review the subject’s medical history for eligibility 
and inclusion into the study.  
 
Female subjects that may be pregnant will undergo a pregnancy test per the individual study sites’ standard 
operating procedures.  
 
The subject will be asked to fill out a NOSE score questionnaire and a NOSE score will be calculated.  If all 
inclusion criteria (including NOSE score ≥55) are met and no exclusion criteria are present, the Investigator 
will inform the subject about the purpose of the study.  The background of the proposed study along with 
the potential benefits and risks will be explained to the subject and questions will be answered.  Potential 
subjects will be counseled as to the nature of their condition. All subjects will have ample time to ask 
questions.  
 
Subjects who indicate they would like to proceed with study participation, and who are willing to comply 
with the requirements of the study protocol, will be asked to sign an Informed Consent Form (ICF) that has 
been approved by the governing IRB.  Failure to provide written informed consent renders the subject 
ineligible for the study.   
 
Subjects that have signed the ICF and meet the eligibility criteria will be scheduled for Visit 2. Subjects will be 
considered enrolled upon signing the ICF and meeting the study eligibility criteria.   
 
Study data should be entered into the EDC within 24 hours of completion of visit.  
 
Subjects that have provided written informed consent and meet the eligibility criteria may also be invited to 
participate in “Latera™ Patient Experience and Testimonials” (see Section 7.2.15).   
 
7.1.2. Baseline Evaluation Visit (Visit 2) 
Baseline visit may occur up to one (1) month prior to procedure visit (Visit 3).  This visit may be completed in 
conjunction with Visits 1 and 3. 
 

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The Investigator will record medical history and concomitant medications on the provided source 
worksheets.  Such history will also include information about previous treatments to further ensure 
compliance with the inclusion and exclusion parameters. 
 
A detailed description of the visit assessments and evaluation methods are located in Section 7.2.  The pre-
intervention data collection will include the following:  
 
1. Nasal Obstruction Symptom Evaluation (NOSE) (See Section 7.2.1) 
2. Baseline Health Economics Questionnaire (See Section 7.2.3) 
3. Demographics & Nasal Medical History (See Section 7.2.5) 
4. Document Concomitant Medications (See Section 8.9) 
5. Baseline Nasal Exam (See Section 7.2.6) 
6. Modified Cottle Maneuver (See Section 7.2.8) 
7. Lateral Wall Motion Video (See Section 7.2.9) 
8. Photography- Cosmetic (selected sites only, See Section 7.2.10) 
9. Photography- 3D (selected sites only, See Section 7.2.11) 
10. NAO Breathing Assessment (See Section 7.2.2) 
11. Assessment of Turbinate Hypertrophy Contribution to NAO (See Section 7.2.12) 
 
Adverse events observed during the baseline visit will be collected and documented. Spirox will be notified 
as necessary pursuant to the description provided in Section 8. Data collected for baseline visits should be 
entered into the EDC no later than seven (7) days after the completion of visit. Upon completion of the 
baseline visit, the subject will be scheduled for Treatment Visit (Visit 3). 
 
7.1.3. Treatment Visit (Visit 3) 
This visit may be completed in conjunction with Visits 1 and 2, and should take place within 1 month after 
Visit 1 (Screening & Enrollment Visit).  If treatment occurs more than 1 month after Visit 1, inclusion and 
exclusion criteria must be re-confirmed and the subject will be asked to re-review, initial and date the ICF to 
continue participation. Subjects will also complete a NOSE scale form.  
 
During this visit, the subject will be treated with the study device according to the Instructions for Use.  The 
procedure will be completed in either a hospital or ASC operating room setting. Only procedure-trained 
investigators that are authorized by the sponsor will be allowed to place the devices during this study. 
 
The following procedures will be completed for the Index procedure visit and placement of the Latera™ 
Implants: 
 
1. Subject will receive general anesthesia, monitored anesthesia care (MAC), or conscious sedation per 
standard operating room procedures. 
2. Amoxicillin or equivalent antibiotic should be administered via either P.O. or IV to the subject before 
the Implant(s) is placed. 
3. Subject will undergo all other planned procedures (e.g., septoplasty and/or turbinate reduction) first, 
with delivery of the Implant(s) being the last step. 
4. The skin of the nose and the nasal mucosal surface should be cleaned and prepped with an antiseptic 
solution (e.g. isopropyl alcohol or betadine ophthalmic). 
5. The nasal anatomy will be examined and target trajectory for the Implant(s) will be established and 
marked with the aid of the implant positioning guide per IFU (Addendum A). 

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6. Images of planned placements should be captured. 
7. Prior to placement of the Implant(s), appropriate topical and local anesthesia should be 
administered to the injection site, depending upon the physician’s judgement; for example a solution 
of 2% Lidocaine with Epinephrine injected locally (1:100,000) may be used.  The anesthesia may be 
injected along the proposed implantation track, starting at the alar rim and progressing to the supra-
periosteal region of the maxilla and along the alar rim at the area of targeted insertion. In addition, 
an infraorbital nerve block may be administered with the same anesthetic solution. 
8. The treatment area should also be pre-treated with an antibiotic ointment (e.g. Mupirocin or 
equivalent) to minimize potential infection risk is recommended. 
9. The implant(s) (unilateral or bilateral) will be delivered per the Spirox IFU20680 (Addendum A). 
Note: Only one Implant per side may be placed. 
 
All medication used during the procedure visit (pre-, during and post-procedure medications) and resource 
utilization will be recorded. 
 
IMPORTANT:  Prior to discharge, subjects will be provided with the post procedure reminder form 
(Addendum F).  In addition, a course of antibiotics (e.g. Amoxicillin, Augmentin or equivalent) may be 
prescribed by the physician pursuant to standard medical practice guidelines. 
 
Planning images captured during procedure will be transferred to sponsor via BrickFTP.com (See Section 
7.2.11 for information on BrickFTP). 
 
Adverse events observed during this visit will be collected and documented. Spirox will be notified as 
necessary pursuant to the description provided in Section 8. Data collected for the Treatment Visit should be 
entered into the EDC no later than even (7) days after the completion of visit.  
 
Upon completion of the baseline visit, the subject will be scheduled for the Follow-Up Visit. 
 
7.1.4. Follow-Up Evaluation Visits (Visit 4-9) 
Safety and performance data will be collected at 1 month (+/- 7 days), 3 months (+/-15 days), 6 months (+/- 
15 days) 12 months (+/- 30 days), 18 months (+/- 30 days) and 24 months (+/- 30 days)  post procedure.  
 
A detailed description of the visit assessments and evaluations are located in Section 7.2.  The following data 
will be collected: 
 
1. NOSE scale (See Section 7.2.1) 
2. NAO Breathing Assessment (See Section 7.2.2) 
3. Subject Satisfaction Questionnaire (See Section 7.2.13)* 
4. Post Procedure Health Economics Questionnaire (See Section 7.2.4)* 
5. Update Concomitant Medications, if changed (See Section 8.9) 
6. Adverse Events since last visit (See Section 8) 
7. Post Procedure Nasal Exam  (see section 7.2.7)* 
8. Lateral Wall Motion Video – 6 Month Visit only (See Section 7.2.9)* 
9. Photography – Cosmetic (select sites only) – 3 and 6 Month Visits only (See Section 7.2.10)* 
10. Photography – 3D (select sites only) – 3, 6 and 12Month Visits only (See Section 7.2.11)* 
 
*This assessment/evaluation will not be collected at the 18 month and 24 month follow ups  

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Adverse events observed through the 12 month visit will be collected and documented. Only adverse device 
effects will be collected beyond the 12 month visit.  Spirox will be notified as necessary pursuant to the 
description provided in Section 8. Data collected for these visits should be entered into the EDC no later than 
seven (7) days after the completion of each visit.  
 
Upon completion of the follow-up visit activities, the subject will be scheduled for the next Follow-up 
Evaluation Visit.   
 
Subject participation will be complete at the 24 month follow-up time point and documented in the Study 
Exit eCRF.   
 
7.2. 
STUDY EVALUATIONS METHODS 
7.2.1. Nasal Obstruction Symptom Evaluation (NOSE) Scale 
The Nasal Obstruction Symptom Evaluation (NOSE) Scale18 is a Patient-Reported Outcome (PRO) instrument 
that will be administered to capture subject perception of the degree of nasal airway patency.  The NOSE 
scale will be completed at the Screening, Baseline, 1 Month, 3 Month, 6 Month, 12 Month, 18 Month and 24 
Month visits.  The NOSE scale may additionally be completed at the Treatment Visit if more than 1 month 
from Screening Visit. 
 
The NOSE scale is a validated instrument, which was developed by the American Academy of 
Otolaryngology—Head and Neck Surgery (AAO-HNS), and has been used in several clinical trials.  The scale is 
brief, easy to complete, and is an important tool for pre- and post-intervention evaluation of symptoms in 
subjects with nasal obstruction.  NOSE Scale allows subjects to quantify their symptoms based on the 
severity of obstruction.   
 
Subjects will be asked, “Since your last follow up visit, how much of a problem were the following conditions 
for you?” Specifically, subjects will be asked to rate their perceptions on the Likert scale with respect to the 
following characteristics: 
 
• 
Nasal congestion or stuffiness 
• 
Nasal blockage or obstruction 
• 
Trouble breathing through my nose 
• 
Trouble sleeping 
• 
Unable to get enough air through my nose during exercise or exertion 
 
Participants will rate their responses using a Likert scale with response options 0, 1, 2, 3 or 4, as follows: 
 
(0) 
Not a Problem 
(1) 
Very Mild Problem 
(2) 
Moderate problem 
(3) 
Fairly Bad Problem 
(4) 
Severe problem 
 
The responses are rated along the continuum, with a rating of “0 – not a problem” indicating no problem 
breathing, with a completely free flow of air through the nasal airway; “1 – very mild problem”, with only 
slight obstruction in airflow; “2 – moderate problem”, with mouth breathing considered easier; “3 – fairly 

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bad problem,” with considerable obstruction to airflow; and a rating of “4 – severe problem,” with complete 
blockage and obstruction of the nasal passageway, where the subject cannot breathe through the nose and 
can only mouth breathe.  A copy of the Nasal Obstruction Symptom Evaluation Scale questionnaire is 
attached (See Addendum B). 
 
7.2.2. NAO Breathing Assessment  
A subject’s perception of breathing cannot be quantitatively measured, but exists on a continuum from the 
subject perspective.  A Visual Analog Scale (VAS) is a patient-reported outcome instrument that will be used 
to capture subjects’ perception of their ability to breathe through the nose, allowing subjects to indicate the 
degree of breathing difficulty (or ease) they are currently experiencing.  The NAO Breathing Assessment will 
be completed at the Baseline, 1 Month, 3 Month, 6 Month, 12, 18 Month and 24 Month visits.   
 
Operationally a VAS is a horizontal line, 100mm in length, anchored by word descriptors at each end, as 
illustrated in Figure 3.    
 
The subject will either mark on the line the point that they feel represents their perception of their current 
state or will communicate the information to the Study Coordinator verbally, who will in turn, mark the form 
as indicated by the subject. The VAS score is determined by measuring in millimeters from the left end of the 
line to the point that the patient marks. 
 
No difficulty/ 
Easy to Breathe 
Through the 
Nose 
 
 
 
Unable to 
Breathe 
Through the 
Nose 
 
 
Figure 3: Visual Analog Scale.  Left side represents 0mm and right side represents 100mm. 
 
7.2.3. Baseline Health Economics Questionnaire  
The baseline health economics questionnaire administered during the baseline visit is a PRO used to assess 
the frequency and type of doctor visits related to the Nasal Airway Obstruction condition over one year prior 
to procedure. 
 
7.2.4. Post Procedure Health Economics Questionnaire  
The post procedure health economics questionnaire administered post-procedure is different from the 
version completed at baseline in the timeframes being referenced.  The post-procedure health economics 
survey will assess frequency and type of doctor visits related to the Nasal Airway Obstruction condition since 
the index procedure.  Do not include visits related to the study when recording the frequency. Subjects will 
complete the Questionnaire at the 1 Month, 3 Month, 6 Month and 12 Month visits.   
 
7.2.5. Demographics & Nasal Medical History 
Demographic information, such as age, gender, ethnicity, race and date of onset of nasal obstruction will be 
ascertained at the baseline visit.   
 

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Relevant nasal medical history will also be captured at the baseline visit and will include a complete review 
of nasal system and evaluation of symptoms, including an assessment of nasal airway obstruction signs and 
symptoms. A history of prior trauma or surgery, including nasal trauma or surgery, will be noted, as well as 
other medical conditions.  Questions will be asked about the medications used by the subjects, including the 
types and doses of medications that are used to control nasal obstruction symptoms and the performance of 
those medications in controlling their symptoms (i.e., OTC medications, nasal sprays, decongestants, nasal 
airway devices, etc.).  
7.2.6. Baseline Nasal Exam 
Nasal exams will be conducted during the baseline visit and will include collection of nasal anatomy 
parameters such as nose length, nose height, width and skin thickness.  In addition, each side of the nose will 
be examined with an endoscope to assess each subject’s degree of inferior turbinate hypertrophy and septal 
deviation (superior and inferior).  Each of these will be graded as Normal, Mild, Moderate, or Severe.  
 
7.2.7. Post Procedure Nasal Exam 
An internal and external nasal physical exam will be conducted at each follow-up visit to document any 
changes in nasal appearance. In addition, during  6 months visit, each side of the nose will be examined with 
an endoscope to assess each subject’s remaining degree of inferior turbinate hypertrophy and septal 
deviation (superior and inferior).  Each of these will be graded as Normal, Mild, Moderate, or Severe.  
 
7.2.8. Modified Cottle Maneuver 
In order to confirm that the subject has dynamic lateral wall insufficiency (LWI), the Modified Cottle 
Maneuver should be performed.  The assessment will be done at the Screening and Baseline visits.   
 
To test for LWI, the curette, cerumen loop, or similar instrument should be inserted into the nasal cavity and 
used to gently support the lateral nasal sidewall while the patient is asked to breathe in.  The Subject will be 
asked to verbally report their relative improvement per side using the scale below (See Figure 4). 
 
No 
Improvement 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Complete 
Improvement 
 
Figure 4: Verbally reported improvement in breathing with supported lateral wall. 
 
7.2.9. Lateral Wall Motion Video 
Using an endoscope, the investigator will record lateral wall motion at rest and at inspiration for each side of 
the nasal vestibule. Videos will be collected at the Baseline and 6 Month follow-up Visits.  Videos will be 
transferred to Spirox and will be blinded prior to transfer to independent reviewer.  The independent 
reviewer will make assessment of endoscopic lateral wall insufficiency score (1, 2 or 3). 
 
Spirox will utilize the HIPPA compliant file transfer protocol website (BrickFTP.com) BrickFTP site for the 
transfer of all images and videos from the site to Spirox for processing and analysis.  Each site will only have 
access to upload and view images in their assigned folder(s) and will not have access to other site’s folders 
on the BrickFTP. 
 
See Addendum C “Lateral Wall Motion Capture Instructions”. 
 

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7.2.10. Photography - Cosmetic 
Review of the nasal appearance changes attributed to the overall procedure as well as those attributed to 
the Latera Implant will be assessed by an independent physician reviewer. 
 
Photographs will be taken to record baseline nose appearance to evaluate aesthetic changes.  Six (6) 
photographs will be taken at baseline, 3, and 6 month time points four (4) static photographic views 
(straight, left side, right side and chin-up) will be taken and two (2) at a full inhale photographic views (chin-
up view and top-down). 
 
Cosmetic photography review will be limited to approximately 3 sites and subject participation is optional.. 
Images will be blinded (e.g. black boxes placed over the eyes) by the sponsor prior to being sent to the 
independent reviewer.  Sites selected for cosmetic review will also be sites participating in 3D Photography 
(see Section 7.2.11).  Images will be transferred using BrickFTP site. 
 
See Addendum D “Cosmetic Photo Capture Instructions”. 
 
7.2.11. Photography – 3D 
3D Image capture will be used to evaluate baseline and post-procedure changes regarding the depth and 
volume of nasal collapse at approximately two sites.  3-D photography review will be limited to 
approximately 3 sites, and subject participation is optional. Site selection for participation will be based on 
adequate facility space and staff to support this additional component.  Subject participation in 3D 
photography is optional. 
 
3D Images will be taken to record baseline NVC of both the left and right side of the nose under static 
conditions and at inhale.  Static and inhales images for both sides will be taken at 3, 6 and 12 month time 
points, to evaluate the change in the nasal collapse depth from baseline.  
 
The Canfield Vectra H1 handheld imaging system allows for the capture and analysis of 3D images.  The 
system is comprised of the Vectra H1 camera, Mirror® software and VECTRA Analysis Module.  The Vectra H1 
camera has an integrated flash to simultaneous capture photographs from dual-angles to build 3-D images. 
Photographs are either captured to the camera’s SD card or tethered to a workstation.  Photographs are 
captured and managed using Canfield Mirror® software and is analyzed with Canfield VECTRA Analysis 
Module.  Images will be saved with the camera-generated sequence number (e.g. photo “38”), and then 
transferred for analysis using the subject ID and study visit for identification.  See Addendum D “3D Imaging 
Procedure” for comprehensive image capture and analysis procedures. 
 
Images will be transferred using BrickFTP site. 
 
See Addendum E “3D Camera Imaging Procedure”. 
 
7.2.12. Assessment of Turbinate Hypertrophy Contribution to NAO 
After completion of all other assessments at the Baseline Visit, subjects will be asked to assess their ability to 
breath after a decongestant (e.g. Afrin) has been administered. Administration of a decongestant is 
frequently used to diagnose significance of inferior turbinate contribution to NAO.  After decongestant 
administration, subjects will be asked to rate their degree of nasal airway obstruction using the VAS scale 
(See Section 7.2.2). 
 

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7.2.13. Subject Satisfaction Questionnaire 
The subject satisfaction questionnaire is a PRO form that will contain the questions related to subject 
satisfaction with the procedure and their nose appearance. Subjects will complete the Questionnaire at the 1 
Month, 3 Month, 6 Month and 12 Month visits.   
 
7.2.14. Discretionary Imaging 
In addition to the protocol specific imaging outlined above, the Investigator may wish to share, or Spirox may 
request, additional images (digital photos) or videos of subject for the purposes of, but not limited to, 
consultation (e.g. placement of device ahead of procedure, etc.), documentation of changes (e.g. cosmetic 
change, lateral wall motion, etc.) or adverse event reporting (e.g. image of hematoma).  Images may include 
endoscopic nasal video, digital video or photography.  Images or videos may be taken at any time point 
during the study.   
 
Digital images will be blinded (e.g. black boxes placed over the eyes).  Images may be used for educational 
and/or research purposes. Images or videos will be transferred to Spirox using BrickFTP.  
 
7.2.15. Latera™ Patient Experience and Testimonials 
Subjects that have enrolled in the study may also be invited to participate in “Latera™ Patient Experience 
and Testimonials”.  This invitation may occur at time of Screening or at any time point through study exit. 
 
Spirox may choose to capture Latera™ patient experience and/or testimonials through film, videotape, 
photographs and/or quotes. Spirox may choose to capture the testimonials prior to, during and after the 
LATERA procedure is performed, at varying intervals (i.e., day of procedure, 1 week post-procedure, 1 month 
post-procedure, etc.). Spirox and the investigational sites may use these photographs, videos, personal 
images and quotes in whatever medium deemed appropriate by Spirox for any of the following purposes: (i) 
educational and research purposes, (ii) medical or audiological consultations, (iii) publication in professional 
journals, (iv) collateral and promotional materials, (v) web-based marketing materials including website 
content, (vi) public and media relations, or any other advertising methodology. 
 
For these subjects, written consent in the form of an IRB approved addendum to the study ICF will be 
required.  Participation is optional and will not impact their participation in the study. Consent to participate 
does not guarantee that they will be selected as a participant.  No additional reimbursement beyond what is 
outlined in Section 5.3 will be provided. 
 
7.3. 
LOST TO FOLLOW-UP 
Site personnel should make reasonable efforts to ensure that all subjects complete the requisite follow up 
visits. A subject will be considered lost to follow-up if the site has:  
 
1. Attempted to contact the subject with a minimum of two phone calls; and  
2. Has mailed a certified letter to the subject.  
 
Before a subject is considered lost to follow up, the above described attempts to contact the subject must be 
documented in the subject’s medical records and in the study CRFs. 
 
 

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7.4. 
STANDARD OF CARE STUDY PROCEDURE 
Per an investigator’s decision, subjects may receive concomitant septoplasty and/or turbinate reductions in 
addition to placement of the Implants to address other potential causes for the nasal airway obstruction.   
 
Septoplasty is a common surgical procedure to correct a deviated septum — a displacement of the bone and 
cartilage that divides the nasal passages. During the procedure, the lining (the mucosa) is first lifted off the 
cartilage and bone. The cartilage and bone can then be reshaped. Sometimes, portions of the cartilage and 
bone need to be removed. The lining is then laid back down. 
 
Turbinate reduction or turbinate resection is a common procedure that is performed alone or in conjunction 
with septoplasty. There are two commonly used approaches to reduce turbinate size: radiofrequency 
reduction, and microdebrider-aided resection using a submucosal approach. With this procedure, the lining 
of the turbinate is left intact, but the tissue from the inside of the turbinate is removed. As the turbinate 
heals, it becomes smaller than before surgery.  
 
Septoplasty and/or turbinate reductions procedures are well established and considered standard of care to 
address respective etiologies. Treatment of the lateral wall with Latera alone or in conjunction with these 
procedures is being evaluated in this study. 
 
7.5. 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES 
Implant procedure may be completed in conjunction with Septoplasty and/or Turbinate reduction 
procedure(s). 
 
Current medications related to the treatment of NAO, NVC, and the management of nasal allergies will be 
documented in the eCRFs. 
 
7.6. 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES 
Concomitant medications or therapies preventing subjects from being eligible to participate in this study are 
current use of nasal oxygen, CPAP, chronic use of systemic steroids and/or recreational intra-nasal drugs.  
Additionally, concomitant radiation exposure in the treatment area or chemotherapy will deem a subject 
ineligible to participate. 
 
In addition, according to the study protocol, the following treatments are not permitted concurrent with 
index procedure or within 24 months after index procedure: 
 
• 
Functional Endoscopic Sinus Surgery (FESS)  
• 
Sinuplasty procedure  
• 
Rhinoplasty procedure 
• 
Any surgical or non-surgical treatment of the nasal valve, other than the index procedure, within 12 
months of the study 
• 
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7.7. 
STUDY SCHEDULE OF EVENTS TABLE 
 
 
 
Study Events 
Screening & 
Enrollment 
(Visit 1) 
Baseline 
Evaluation 
(Visit 2)1 
Treatment 
(Visit 3) 
Follow Up 
1 mo 
(Visit 4) 
Follow Up 
3 mo 
(Visit 5) 
Follow Up 
6 mo 
(Visit 6) 
Follow Up 
12 moStudy 
Visit 
(Visit 7) 
Follow Up 
18 & 24 
mo/Final 
Study Visit 
(Visits 8 & 
9) 
Early 
Exit 
Secure Informed Consent 
X 
 
 
 
 
 
 
 
 
Secure Re-Consent for 18M and 24M 
Follow Up 
 
 
 
 
 
 
X 
 
 
Inclusion/Exclusion 
X 
 
X2 
 
 
 
 
 
 
NOSE Scale (PRO) 3 
X  
X 
X2 
X 
X 
X 
X 
X 
 
NAO Breathing Assessment (PRO) 
 
X 
 
X 
X 
X 
X 
X 
 
Subject Satisfaction Questionnaire (PRO) 
 
 
 
X 
X 
X 
X 
 
 
Health Economics Questionnaire (PRO) 
 
X 
 
X 
X 
X 
X 
 
 
Nasal Medical History/Nasal Geometry 
 
X 
 
 
 
 
 
 
 
Nasal Exam 
 
X 
 
X 
X 
X 
X 
 
 
Lateral Wall Motion Video  
 
X 
 
 
 
X 
 
 
 
Photography- 3D Camera (select sites) 
 
X 
 
 
X 
X 
X 
 
 
Photography –Cosmetic (select sites) 
 
X 
 
 
X 
X 
 
 
 
Turbinate Hypertrophy Contribution to 
NAO assessment (Nasal Decongestant) 
 
X 
 
 
 
 
 
 
 
Photography – Planning Images 
 
 
X 
 
 
 
 
 
 
NAO Treatment 
 
 
X 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
X 
X 
X 
 
 
Adverse Event Assessment 
 
 
X 
X 
X 
X 
X 
 
X  
Adverse  Device Effects Assessment 
 
 
 
 
 
 
 
X 
 
Complete Study Exit Form 
 
 
 
 
 
 
 
X4 
X 
 
                                                          
1 Visit 2 activities may be done in conjunction with Study Visit 1.  In this instance, the Screening NOSE Scale is not required. 
2 If Visit 3 (Treatment Visit) is more than 1 month after Visit 1, inclusion/exclusion criteria need to be re-confirmed.  Additionally, subjects should be asked to review IC 
form, initial and date the IC document to confirm continued consent for participation, and complete NOSE scale. 
3 If Visits 1, 2 and 3 are done on the same day, the Screening and Treatment NOSE Scales are not required. 
4To be completed at 24M follow up.  

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7.8. 
EARLY TERMINATION VISIT 
In the event of an early subject termination, the clinical site should, at a minimum, document Adverse Events 
and Concomitant Medications changes.  The clinical site will additionally complete the Study Exit eCRF. Refer 
to Section 7.7 Schedule of Events. 
 
8. 
ASSESSMENT OF SAFETY 
8.1. 
SPECIFICATION OF SAFETY PARAMETERS  
All Serious Adverse Events (SAE), Adverse Device Effect (ADE) and Serious Adverse Device Effects (SADE) will 
be collected and documented through the end of subject participation in the study.   In addition, all non-
serious device and procedure-related Adverse Events (AE) and all non-serious head and neck, and/or 
respiratory related AEs will also be collected and documented. 
 
The primary safety endpoint evaluation will consider nasal procedure related and Latera related adverse 
events through 6 months post-procedure. 
 
The following information for each AE, ADE, SAE and SADE will be collected: 
 
• 
Date of onset 
• 
Status and/or Outcome 
• 
Date of resolution 
• 
Adverse Event/Effect type 
• 
SAE or SADE 
• 
Severity of event 
• 
Relation to Study Device and/or procedure 
• 
Action taken 
• 
Descriptive narration of Event/Effect 
 
8.1.1. DEFINITION OF ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) 
An adverse event (AE) or effect is defined as any untoward and unintended medical occurrence experienced 
by a clinical study subject.  An AE can therefore be any unfavorable and unintended sign, symptom, or 
disease temporally associated with the use of the investigational product, whether or not related to the 
product. 
 
The following events will be considered to be serious adverse events (SAE) and must immediately and 
without delay (within 24 hours) be reported to the study Sponsor by fax and/or email.  These events must be 
reported whether or not the Investigator believes they are related to study procedures, activities or device: 
 
• 
Death (the investigator will provide a copy of any post-mortem findings, including histopathology 
reports if available).  
• 
Life-threatening event or injury 
• 
Disability – significant, persistent, or permanent change, impairment, or damage or disruption in the 
subject’s body function/structure, physical activities or quality of life 
 
 

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• 
Necessitate immediate medical or surgical intervention to: 
o Preclude permanent impairment of a body function or permanent damage to a body 
structure; or 
o Relieve unanticipated temporary impairment or damage. 
• 
Prolongation of a hospitalization 
• 
New hospitalization 
 
8.1.2. DEFINITION OF ADVERSE DEVICE EFFECT (ADE) AND SERIOUS ADVERSE DEVICE EFFECT 
(SADE) 
An Adverse Device Effect (ADE) is defined as any untoward or unintended response to a medical device. This 
definition includes any event resulting from insufficiencies or inadequacies in the instructions for use or the 
deployment of the device. This definition also includes any event that is a result of user error. A Serious 
Adverse Device Effect (SADE) is an adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event or that might have led to any of these consequences if suitable 
action had not been taken or intervention had not been made or if circumstances had been less opportune. 
All SADEs must immediately and without delay (within 24 hours) be reported to the study Sponsor by fax 
and/or email. 
 
8.1.3. DEFINITION OF UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) 
An unanticipated adverse device effect (UADE) is defined as 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 (including a supplementary 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 812.3(s)). 
 
8.2. 
CLASSIFICATION OF AN ADVERSE EVENT 
8.2.1. SEVERITY OF EVENT 
The following guidelines will be used to describe the severity of an event: 
 
• 
Mild – Awareness of the event, may cause no or minimal interference with the subject’s daily life. 
• 
Moderate – Discomfort enough to cause a noticeable impact on the subject’s daily life.  
• 
Severe – Incapacitation or significant impact on the subject’s daily life. 
 
8.2.2. RELATIONSHIP TO STUDY DEVICE/PROCEDURES 
Two types of relationships will be assessed: 
 
1. Related to the Latera device or Latera device-specific procedure, including Implant delivery 
2. Related to concomitant procedures, such as septoplasty and turbinate reduction 
 
The clinician’s assessment of an AE's relationship to the study device, implant procedure and/or the 
concomitant procedure(s) is part of the documentation process, but it is not a factor in determining what is 
or is not reported in the study. If there is any doubt as to whether a clinical observation is an AE, the event 
should be reported. All AEs must have their relationship to the Latera study device or Latera device 
procedure assessed.  
 

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For all collected AEs, the clinician who examines and evaluates the subject will determine the AE’s causality 
based on temporal relationship and his/her clinical judgment. The degree of certainty about causality will be 
graded using the categories below. 
 
• 
Definitely Related – The event is definitely related to the study device/procedure or concomitant 
procedure 
• 
Probably Related – The event is probably related to the study device/procedure or concomitant 
procedure; or the event cannot be explained by other condition or illness. 
• 
Possibly Related – The event is possibly related to the study device/procedure or concomitant 
procedure, but not likely. 
• 
Unlikely Related – The event is unlikely related to the study device/procedure or concomitant 
procedure. 
• 
Not Related – The event is definitely not related to the study device/procedure or concomitant 
procedure. 
 
8.2.3. EXPECTEDNESS 
The Medical Monitor will be responsible for determining whether an AE is expected or unexpected. An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the device as well as concomitant procedures (septoplasty and/or 
turbinate reduction).  
 
Refer to section 2.3.2 for list of expected risks. 
 
8.3. 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a subject presenting for medical care, or upon review by a study monitor. 
 
All device or procedure-related AEs, including local and systemic reactions not meeting the criteria for SAEs, 
will be captured on the appropriate CRF. Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis) or concomitant procedures, and time of resolution/stabilization 
of the event. All AEs occurring while on study must be documented appropriately regardless of relationship. 
All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time of the participant’s procedure will be considered as a 
baseline condition or comorbidity, and will not reported as an AE. However, if the subject’s condition 
deteriorates at any time during the study, and the condition is procedure/device related, it will be recorded 
as an AE. AEs will be recorded in the data collection system throughout the study. 
 
Changes in the severity of an AE will be documented. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
 
At each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. Events 
will be followed for outcome information until resolution or stabilization. 
 
 

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8.4. 
REPORTING PROCEDURES 
8.4.1. ADVERSE EVENT REPORTING 
The investigator must document all AEs on the AE Source Documents and subsequently enter this 
information into the electronic case report form, which will be reviewed by the study monitor and provided 
to the study sponsor.  AE source documentation must be signed off by the procedure-trained investigator.  
 
8.4.2. SERIOUS ADVERSE EVENT REPORTING 
The study investigator must report all SAEs and SADEs to the study sponsor immediately and without delay 
within 24 hours of site awareness and complete a AE CRF.  See Section 1, clinical monitoring, for primary 
contact information. 
 
All SAEs and SADEs will be followed until satisfactory resolution or until the site PI deems the event to be 
chronic or the adherence to be stable. Other supporting documentation of the event may be requested by 
the study sponsor and should be provided as soon as possible. 
 
The study sponsor will be responsible for notifying FDA of SAEs pursuant to the MDR reporting 
requirements (21 CFR 803.19(a)(2)). 
 
8.4.3. UNANTICIPATED PROBLEM REPORTING 
An investigator shall submit to the sponsor and to the reviewing IRB a report of any Unanticipated Adverse 
Device Effect (UADE) occurring during an investigation as soon as possible, but no later than ten (10) working 
days after the investigator first learns of the effect (21 CFR 812.150(a)(1)). 
 
A sponsor who conducts an evaluation of an unanticipated adverse device effect under 812.46(b) shall report 
the results of such evaluation to FDA pursuant to the MDR regulations and to all reviewing IRB's and 
participating investigators within tent (10) working days after the sponsor first receives notice of the effect.  
 
8.5. 
STUDY HALTING RULES 
Circumstances that may warrant termination or suspension include, but are not limited to the following 
unlikely events: 
 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol  
• 
Determination that it is unlikely that the study null hypothesis can be rejected 
 
8.6. 
SAFETY OVERSIGHT 
Adverse events will be reviewed periodically by the Medical Monitor.  For any reported SAE, the Medical 
Monitor and Scientific Advisory Board members will review the relevant materials and may issue a 
recommendation to terminate the study as described above.  
 
If this recommendation is reached, then the PI, study sites and IRBs will be notified. In addition, Spirox will 
follow the MDR reporting requirements pursuant to (21 CFR 803.19(a)(2)). 
 
 
 

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9. 
CLINICAL MONTIORING 
Clinical monitoring and oversight of the study will be conducted by Spirox, to ensure that the safety, rights 
and well-being of human subjects are protected, that the reported trial data are accurate, complete, and 
verifiable, and that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with applicable regulatory requirement(s). 
 
The clinical site monitoring plan for this study will utilize both on-site and centralized (remote) monitoring, 
with on-site visits occurring early in site enrollment and continuing throughout the study as deemed 
necessary.  Data verification will consist of 100% Source Document Verification of primary and secondary 
endpoint data and adverse device effects through 6 months, verification of correct ICF execution, subject 
eligibility, and compliance with the protocol.   .  Clinical monitoring for the remainder of the data collected 
includes CRF reviews for timing, completeness and consistency of the CRF data for each subject through 
study exit.  Onsite visits are documented including letters to the site principal investigator for visit planning 
and for a summary of any visit observations. 
 
An independent audit of Clinical Study File at Sponsor’s site may be conducted during the course of the 
study. 
 
10. 
STATISTICAL CONSIDERATIONS 
10.1. STATISTICAL AND ANALYTICAL PLANS 
A Statistical Analysis Plan (SAP) will be finalized prior to database lock, which will contain further analysis 
details and statistical methods. 
 
10.2. STATISTICAL HYPOTHESES 
Primary Efficacy Endpoint: 
 
• 
The primary efficacy endpoint is the proportion of treatment responders at 6 months post 
procedure. Since there is no direct comparison group in this study, the primary efficacy hypothesis is 
a superiority comparison to a target proportion: 
 
Null Hypothesis H0: the proportion of responders at 6 months is = 0.50, versus 
Alternative Hypothesis HA: the proportion of responders at 6 months is ≠ 0.50  
 
• 
There are no other formal statistical hypotheses. 
 
10.3. ANALYSES DATASETS 
Three analysis populations will be considered: 
 
• 
Intention-to-Treat (ITT) Population: all enrolled subjects who began a nasal Implant procedure  
• 
Modified Intention-to-Treat (mITT) Population: all subjects enrolled who received at least one 
nasal Implant 
• 
Per-Protocol (PP) 6 Month Evaluable Population: subjects with 6 month post-Implant NOSE 
score assessments in clinic or by telephone 
 
 
 

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10.4. DESCRIPTION OF STATISTICAL METHODS 
10.4.1. GENERAL APPROACH 
This is a prospective, single arm, open label controlled study to evaluate the impact of Spirox Latera™ alone 
or in conjunction with other procedures over 24 months of follow-up.  Each patient will serve as his or her 
own control. 
 
The study reference day (Day 1) is the day of the Implant procedure.  
 
“Baseline” NOSE score refers to the measurement taken prior to the start of the procedure during the 
baseline visit. 
 
Continuous variables will be summarized with descriptive statistics (N, mean, SD, median, quartiles), and 
categorical variables will be summarized as N (%). 
 
Unless otherwise indicated, all p-values and confidence intervals will be 2-sided. 
 
10.4.2. ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
The primary endpoint will be the proportion of treatment responders at 6 months post procedure.  
 
Responder is defined as subject that has at least one (1) NOSE class improvement or at least 20% NOSE score 
reduction  
 
Subjects will be classified as non-responders if neither of these criteria is met. 
 
NOSE score is a patient-reported outcome instrument which measures the impact of nasal obstruction on 
quality of life. It is scored in increments of 5 points, and the total score is calculated as the sum of all 5 
questions multiplied by 5, where the range is 0 (asymptomatic) to 100 (most extreme deleterious impact on 
quality of life). The NOSE score classes16 are based on the total calculated score: 
 
Mild: 5 – 25 points 
Moderate: 30 – 50 points 
Severe: 55 – 75 points 
Extreme: 80 – 100 points 
 
This primary hypothesis will be evaluated for the 6 Month Evaluable Population using a -2-sided exact test23, 
and the corresponding exact (Clopper-Pearson) 2-sided 95% confidence interval will be calculated. The null 
hypothesis that the proportion of responders is ≠ 0.5 will be rejected if the p-value is < 0.05. 
 
Sensitivity analyses will be conducted to determine the impact of missing data on these results. These 
analyses will depend on the extent of missing data, and will be detailed in the SAP, but may include: 
 
1. Last observation carried forward (LOCF) 
2. Subjects with missing data classified as non-responders 
 
10.4.3. ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Response proportion as defined in section 10.4.2 will be evaluated for the 1, 3,6, 12, 18 and 24 month 
follow-up visits using the same technique as described for the primary endpoint. 

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Change in nasal airway obstruction from baseline at 1,3, 6, 12, 18 and 24 months post-procedure as reported 
by subjects on a VAS 0-100 mm scale (0= no difficulty breathing through nose; 100mm=not-able to breathe 
through nose) will be analyzed using a mixed model for repeated measures (MMRM). Least-square mean 
change from baseline and corresponding 95% confidence intervals will be reported. Baseline VAS score will 
be analyzed in a separate model, including decongestant use as a covariate.  Decongestant use will be 
considered at baseline only to visualize the turbinate contribution to overall obstruction, thus no 
decongestant VAS will be assessed at the follow-up visits. 
 
Results from the subject satisfaction questionnaire will be tabulated at 6 months. Sensitivity analyses for 
missing data will be described in the SAP. 
 
10.4.4. SAFETY ANALYSES 
Two analysis sets will be used to summarize adverse events. The ITT analysis set will be used to summarize 
acute adverse events (through 1 month post procedure), and the mITT analysis set will be used to summarize 
adverse events over the entire duration of follow-up. The primary safety reporting time-point is 6 months 
post-implant. 
 
The overall incidence (i.e., number and percent of subjects with 1 or more adverse event in each class) of 
adverse events, serious adverse device events, serious adverse events, fatal adverse events, and device 
related events (e.g., possibly, probably or definitely related) will be calculated for the acute phase, through 6 
months post-procedure and for the entire duration of follow-up. The overall incidence of mild, moderate and 
severe events will be calculated by considering the most severe event for each subject. 
 
In addition, the overall incidence for each adverse event type will be calculated. The adverse event types will 
be classified according to the following categories: 
 
• 
Excessive Inflammation 
• 
Significant Foreign body sensation 
• 
Excessive Pain or discomfort 
• 
Infection 
• 
Implant Extrusion, defined as body rejection of implants 
• 
 Implant Retrievals, defined as surgeon or subject initiated removal of implants not associated with 
body rejection of implant  
• 
Implant bent or fractured 
• 
Implant loose 
• 
Implant migration 
• 
Skin irritation 
• 
Hematoma 
• 
Unintended perforation of the skin 
• 
Other 
 
10.4.5. ADHERENCE AND RETENTION ANALYSES 
Protocol deviations will be tabulated. Baseline demographic and medical history will be tabulated by 
whether the 6 month NOSE score data are available or missing to identify potential systematic differences 
between subjects with and without 6 month follow-up scores. 
 

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10.4.6. BASELINE DESCRIPTIVE STATISTICS 
Baseline characteristics, including demographic characteristics, medical history, patient-reported outcomes 
and physical measurements will be summarized using descriptive statistics.  
 
10.4.7. PLANNED INTERIM ANALYSES 
No interim analyses with formal stopping implications will be performed, though changes in NOSE score 
may be aggregated to facilitate sample size calculations for future studies. 
 
10.4.7.1. SAFETY REVIEW 
All adverse events will be reviewed by the Medical Monitor.  For any reported SAE, the Medical Monitor and 
Scientific Advisory Board members will review the event and issue a recommendation. 
 
The study sponsor will be responsible for notifying FDA of SAEs pursuant to the applicable MDR 
reporting requirements 21 CFR 803. 
 
10.4.7.2. EFFICACY REVIEW 
No interim analyses with formal stopping implications will be performed, though changes in NOSE score may 
be aggregated prior to database lock to facilitate sample size calculations for future studies. As there is no 
opportunity to stop early for efficacy or to alter the study design based on this calculation, there will be no 
type 1 error adjustment for this analysis. 
 
10.4.8. ADDITIONAL SUB-GROUP ANALYSES 
Response percentage, change in NOSE scores and other variables including satisfaction will also be evaluated 
in the following subgroups: 
 
• 
Turbinate reduction method:  radiofrequency versus mechanical 
• 
Time-dependent presence or absence of allergic rhinitis 
• 
Nasal geometry factors 
o Nose length (above or below median) 
o Nose width (above or below median) 
o Categorical skin thickness 
 
10.4.9. MULTIPLE COMPARISON/MULTIPLICITY 
No formal type 1 error adjustment will be made for the analysis of secondary and exploratory endpoints. All 
endpoints except for the primary endpoint should be considered supportive, and inference should be drawn 
with caution. 
 
10.4.10. 
TABULATION OF INDIVIDUAL RESPONSE DATA 
Listings of adverse events may be produced. 
 
10.4.11. 
EXPLORATORY ANALYSES 
Cosmesis changes from baseline to 3 month and 6 months, evaluated by Independent Photo Review at 2 
sites only, will also be tabulated. 

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Endoscopic lateral wall insufficiency score is a 3-level, categorical variable, which will be evaluated for each 
side separately.  Baseline and 6 month post-baseline scores will be cross-tabulated, and the proportion with 
improvement will be calculated. 
 
Response percentage, change in NOSE scores and other variables including satisfaction will also be evaluated 
by type of procedure (implant alone versus combinations with septoplasty and/or turbinate reductions). 
 
Resource use will also be summarized. 
 
10.5. SAMPLE SIZE 
The primary study hypothesis is a superiority comparison to a target proportion: 
 
Null Hypothesis H0: the proportion of responders at 6 months is =0.50, versus 
Alternative Hypothesis HA: the proportion of responders at 6 months is ≠ 0.50  
 
See section 10.4.2 for the definition of response. This hypothesis will be evaluated using an exact test. 
 
In order to have > 90% power to rule out a response rate ≤ 50% at a 5% (2-sided) significance level, assuming 
a true response rate of 66%, 150 subjects with 6 month follow-up are needed. Assuming about 10% drop-
out rate, up to 170 subjects will be enrolled. All mITT subjects will be used for this comparison, regardless of 
protocol deviations. 
 
The assumed response rate is the minimum value expected to be consistent with previous trials, where an 
80% response rate at 6 months was observed. 
 
Sample size calculations were performed using the package RCTDesign for R version 3.2.3. 
 
10.6. MEASURES TO MINIMIZE BIAS 
This is a single arm, open label study. Randomization and blinding are not used. 
 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Each participating site will maintain appropriate medical and research records for this trial, in compliance 
with ICH E6 and regulatory and institutional requirements for the protection of confidentiality of 
participants. Each site will permit authorized representatives of the study sponsor and regulatory agencies 
to examine (and when permitted by applicable law, to copy) clinical records for the purposes of quality 
assurance reviews, audits, and evaluation of the study safety, progress, and data validity.  
Source data includes all information, original records of clinical findings, observations, or other activities in 
a clinical trial necessary for the reconstruction and evaluation of the trial. Examples of these original 
documents and data records include, but are not limited to, hospital records, clinical and office charts, 
laboratory notes, memoranda, participants’ memory aids or evaluation checklists, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate and 
complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, and participant files 
and records kept at the pharmacy, at the laboratories, and medico-technical departments involved in the 
clinical trial. Sponsor will provide Source Documents to the sites. 
 
For each subject consented, the inclusion/exclusion source documentation must be signed by the 
investigator or authorized delegate from the trial staff. If a subject withdraws from the study, the reason 

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must be noted on the Study Exit eCRF. If a Subject is withdrawn from the study because of a treatment-
limiting adverse event, thorough efforts should be made to clearly document the outcome. 
 
All forms shall be filled out using indelible ink and must be legible. Errors shall be crossed out but not 
obliterated and correction inserted and the change initialed and dated by the investigator or authorized 
delegate. The investigator shall ensure accuracy, completeness, legibility and timeliness of the data reported 
to the sponsor in the eCRF and in all required reports. 
 
Each investigator/institution agrees that they will permit trial-related monitoring, audits, IRB review and 
regulatory inspections by providing direct access to source data and/or documents. 
 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL 
Regular monitoring will be performed according to ICH-GCP. See also Section 9, Clinical Monitoring. 
 
Quality Control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory 
requirements (e.g., Good Manufacturing Practices (GMP)). 
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 
 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1. ETHICAL STANDARD 
The site PI will ensure that this study is conducted in full conformity with Regulations for the Protection of 
Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or the ICH E6 
and the Declaration of Helsinki. 
 
13.2. INSTITUTIONAL REVIEW BOARD 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and approval 
by the IRB before the changes are implemented to the study. All changes to the consent form will be IRB 
approved; a determination will be made regarding whether previously consented participants need to be re-
consented. 
 
13.3. INFORMED CONSENT PROCESS 
13.3.1. CONSENT AND OTHER INFORMATIONAL DOCUMENTATION PROVIDED TO PARTICIPANTS 
Consent forms describing in detail the study device, study procedures, and risks are given to the participant 
and written documentation of informed consent is required prior to starting study-related procedures.  Site-
specific Informed Consent Form will be submitted with this protocol for IRB review and approval. 

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13.3.2. CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Potential risks and benefits of participation 
will be discussed with the participants. Consent forms will be IRB-approved and the participant will be asked 
to read and review the document. The investigator will explain the research study to the participant and 
answer any questions that may arise. All participants will receive a verbal explanation in terms suited to their 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as research 
participants. Participants will have the opportunity to carefully review the written consent form and ask 
questions prior to signing. 
 
The participant will sign the informed consent document prior to any procedures being done specifically for 
the study. The participants may withdraw consent at any time throughout the course of the trial. A copy of 
the informed consent document will be given to the participants for their records. The rights and welfare of 
the participants will be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study. 
 
A Subject Research Participation Note will be filed in the subject’s medical record, documenting that the 
informed consent process occurred and the subject voluntarily provided written informed consent to 
participate in the study. 
 
13.4. PARTICIPANT AND DATA CONFIDENTIALITY 
All information concerning subjects or their participation in this trial will be considered confidential and 
maintained in compliance with the HIPAA Rules.  Only authorized study sponsor personnel and designated 
consultants will have access to these confidential files.  Authorized regulatory personnel have the right to 
inspect and copy all records pertinent to this trial.  Enrolled subjects will be assigned a unique identifier that 
will be used to maintain confidentiality of subjects’ medical information.  Subject names and other protected 
health information will not be captured on the case report forms. 
 
The sponsor, its designee, or representatives of the IRB may inspect all documents and records required to 
be maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) 
and pharmacy records for the participants in this study. The clinical study site will permit access to such 
records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use during 
the study. At the end of the study, all records will continue to be kept in a secure location for as long a period 
as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at MedNet Solutions, the EDC system provider utilized for this study. This will not 
include the participant’s contact or any identifying information. Rather, individual participants and their 
research data will be identified by a unique study identification number. The study data entry and study 
management systems used by clinical sites, Spirox, and any third party vendor contacted by Spirox to 
perform data management activities and/or statistical analysis will be secured and password protected.  The 
identity of a subject will never be disclosed in the event that the study data are published. 
 
 
 

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13.5. COMPENSATION FOR INJURY 
In the event that a subjects is injured as a result of the Latera™ Implant procedure done for the purpose of 
this study, the sponsor will pay for those medical expenses that are necessary to treat injuries that are not 
covered by subject’s medical insurance or any other third party coverage provided that the Latera 
Absorbable Nasal Implant was implanted following this study protocol, the instructions for use and the 
cleared indications for use (i.e., for supporting the upper and/or lower lateral nasal wall cartilage).  There are 
no plans to provide other compensation beyond that which is described herein or in the informed consent 
document.   
 
14. 
DATA HANDLING AND RECORD KEEPING 
14.1. DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. 
The investigator is responsible for ensuring the accuracy, completeness, and timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. When making changes or corrections, cross out the original entry with a single line, and initial and date 
the change. DO NOT ERASE, OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Data reported in the eCRF should be consistent with the source documents or the discrepancies should be 
explained and captured in the eCRF comments section and maintained in the participant’s official electronic 
study record. 
 
Clinical data (including concomitant medications, and adverse events data) will be entered into iMedNet, a 
21 CFR Part 11-compliant data capture system provided by MedNet Solutions.  
 
The data system includes password protection and internal quality checks, such as automatic range checks, 
to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly 
from the source documents. 
 
14.2. STUDY RECORDS RETENTION 
Study documents should be maintained in a professional manner and in compliance with the HIPAA Rules as 
applicable, so as to permit review the Study records, documents, information, data, and materials in full 
without disclosing to Sponsor any third party confidential or proprietary information.  Site shall maintain all 
such records for the Study for a period of 2 years after the latter of the following two dates: The date on 
which the investigation is terminated or completed, or the date that the records are no longer required for 
purposes of supporting a premarket approval application or a notice of completion of a product 
development protocol.  No records will be destroyed without the written consent of the sponsor, if 
applicable. It is the responsibility of the sponsor to inform the investigator when these documents no longer 
need to be retained.  Spirox will maintain records according to the company’s record retention policy. 
 
14.3. PROTOCOL DEVIATIONS 
A protocol deviation is any noncompliance with the clinical trial protocol or GCP requirement. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly. 
 

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These practices are consistent with ICH E6: 
 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 
5.1 Quality Assurance and Quality Control, section 5.1.1 
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site to use continuous vigilance to identify and report significant deviations of 
identification of the protocol deviation to the study Sponsor. All deviations must be documented on a 
protocol deviation eCRF. Protocol deviations must be sent to the local IRB per the IRB’s reporting 
requirements. The site PI/study staff is responsible for knowing and adhering to their IRB requirements.  
 
14.4. PUBLICATION AND DATA SHARING POLICY 
Authorship and manuscript composition will reflect joint cooperation between the investigator, the study 
sites, and the study Sponsor. No individual publications will be allowed prior to completion of the final report 
of the study except as agreed with the study Sponsor. Additional details of data sharing policy can be found 
in each site’s Clinical Trial Agreement. 
 
The sponsor request that all publications are reviewed and approved prior to submission to publication. 
 
The study Sponsor will register and report the results of the study on ClinicalTrials.gov. 
 
15. 
STUDY ADMINISTRATION 
15.1. STUDY LEADERSHIP 
The Study Team will oversee the conduct of the study.  The Study team will be composed of representatives 
of the Sponsor including the Medical Monitor, and the study Principal Investigators.  The Study Team will 
meet periodically to review study progress and any available results.  
 
16. 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect of 
this trial will be disclosed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the trial. Spirox has 
established policies and procedures, including those pertaining to the Sunshine Act, to disclose conflicts of 
interest and will establish a mechanism for the management of all reported dualities of interest. 
 
17. 
LITERATURE REFERENCES 
 
1. Mink PJ. Physiologie der Obern Luftwege. Leipzig. Germany: Vogel; 1920. 
2. Becker SS, Dobratz EJ, Stowell N, et al Revision septoplasty: Review of sources of persistent nasal 
obstruction Am J Rhino. 2008; 22:440-444  
3. Most SP.  Trends in functional rhinoplasty. Arch Facial Plast Surg. 2008;10(6):410-413 
4. Most SP.   Comparing Methods for Repair of the External Valve: One More Step Toward a Unified View of 
Lateral Wall Insufficiency, JAMA Facial Plastic Surgery 2015 Sep-Oct;17(5):345-6 

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5. Stewart MG, Smith TL, Weaver EM et al.  Outcomes after nasal septoplasty: results from the Nasal 
Obstruction Septoplasty Effectiveness (NOSE) study Otolaryngol Head Neck Surg; 2004;130(3):283-90. 
6. Lavinsky-Wolff M, Camargo HL Jr, Barone CR,  et al Effect of turbinate surgery in rhinoseptoplasty on 
quality-of-life and acoustic rhinometry outcomes: a randomized clinical trial. Laryngoscope. 
2013;123(1):82-9    
7. Sufyan A, Ziebarth M, Crousore N et al Nasal batten grafts: are patients satisfied? Arch Facial Plast Surg. 
2012;14(1):14-9.  
8. Murrell GL 2004 Auricular cartilage grafts and nasal surgery Laryngoscope. 2004;114(12):2092-102. 
9. Cochran CS, Ducic Y and DeFatta RJ. Restorative rhinoplasty in the aging patient Laryngoscope. 2007 
;117(5):803-7. 
10. Islam A1, Arslan N, Felek SA et al Reconstruction of the internal nasal valve: modified splay graft 
technique with endonasal approach. Laryngoscope. 2008;118(10):1739-43. 
11.  Toriumi DM, Josen J, Weinberger M, et al. Use of alar batten grafts for correction of nasal valve 
collapse. Arch Otolaryngol Head Neck Surg. 1997:123802–123808 
12. Akcam T, Friedman O and Cook TA. The effect on snoring of structural nasal valve dilatation with a 
butterfly graft. Arch Otolaryngol Head Neck Surg. 2004;130(11):1313-8. 
13. Winkler AA, Soler ZM, Leong PL, et al “Complications Associated With Alloplastic Implants in 
Rhinoplasty,” Arch Facial Plast. Surg., 2012; 14(6):437-441  
14. Ramakrishnan JB, Danner CJ, and Yee SW “The use of porous polyethylene implants to correct nasal 
valve collapse,” Otolaryngology – Head and Neck Surg. 2007 136: 357-361  
15. Rhee JS, Sullivan CD, Frank DO, et al. “A systematic review of patient reported nasal obstruction scores: 
Defining normative and symptomatic ranges in surgical Subjects,” JAMA Facial Plast. Surg., 2014, 16 
(3):219-232  
16. Khosh MM, Jen A, Honrado C et al.Nasal valve reconstruction: experience in 53 consecutive patients Arch 
Facial Plast Surg. 2004;6(3):167-171 
17. Lipan MJ, Most SP. Development of a severity classification system for subjective nasal obstruction. 
JAMA Facial Plastic Surg. 2013 15(5):358-61 
18. Stewart MG, Witsell DL, Smith TL, et al.“Development and Validation of the Nasal Obstruction  
Septoplasty Effectiveness (NOSE) Scale,” Otolaryngology - Head and Neck Surgery, 2004 ; 130; 2:157-163 
19. Bhattacharyya, “Ambulatory Sinus and Nasal Surgery in the United States: Demographics and 
perioperative outcomes.  Laryngoscope 120:635-638, 2010. 
20. Matthias “Surgery of nasal septum and turbinates” GMS Current topics in Otolaryn. Head and Neck 
Surgery 2007, vol. 6. 
21. Tsao GJ, Fijalkowski N, Most SP.  Validation of a grading system for lateral nasal wall insufficiency. Allergy 
Rhinol (Providence). 2013 Summer;4(2). 
22. Landes CA, Ballon A and Roth C. In-Patient Versus In Vitro Degradation of P(L/DL)LA and PLGA J Biomed 
Mater Res B Appl Biomater. 2006 76(2):403-11. 
23. Myles Hollander & Douglas A. Wolfe (1973), Nonparametric Statistical Methods. New York: John Wiley & 
Sons. Pages 15–22. 
 
 

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APPENDIX I – PROTOCOL REVISION HISTORY 
 
 
Version 
Date 
Significant Revisions 
0.1 
22July2016 
Initial Protocol Release 
0.2 
27Jul2016 
Addition of Inclusion Criteria 8: Previous medical 
management. 
0.3 
22Aug2016 
Amendment applies to all subjects/sites, consented on or 
after approval date. 
• 2.2 Prior Investigation data updated. 
• 2.3.2 Potential Risks & Benefits updated/clarified. 
• 4.2 Study Endpoints - VAS scale corrected. 
• 5.1 Inclusion Criteria #8 refined. 
• 6. Study Device section updated. 
• 7. Study Procedures and Schedule clarified. 
• 8.1 Specification of Safety Parameters clarified. 
• 13.5 Compensation for Injury - Section added. 
• Administrative corrections/updates.  
1.0 
13Dec2016 
Amendment applies to all subjects/sites, consented on or 
after approval date. Subjects consent prior to amendment will 
be re-consented. 
• Appendix II – Nonsignificant Risk Rationale added. 
• 4.2.1 Clarification of Primary endpoint. 
• MAC/Conscious sedation 
• Consent for patient experience and additional imaging 
• Discharge instructions  
• Increased number of sites 
• Inclusion criteria 8 clarified 
• Exclusion criteria 4 updated 
• Exclusion criteria 21 added 
• Schedule of events clarified to allow screening, baseline and 
treatment in one day 
• Schedule of events clarified to only need 1 NOSE score if 
screening, baseline and treatment are less than 30 days 
apart 
• Study procedures re-organized into section on visits and 
evaluation methods for clarity 
• Administrative corrections/updates 
1.1 
16Dec2016 
• Limited  frequency of evaluation of degree of inferior 
turbinate hypertrophy and septal deviation to baseline 
and 6 months nasal exams 
1.2 
07Sept2017 
• Addition of 18 month and 24 month follow up evaluations 
 
 
 

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APPENDIX II – NONSIGNIFICANT RISK RATIONALE 
 
Background 
1. The Latera™ System (Absorbable Nasal Implant and Delivery Device) is a commercially available device 
that received FDA clearance on June 23, 2016 (K161191). The device is indicated for “supporting nasal 
upper and lower lateral cartilage.” Clinical performance data was submitted in support of the initial 
Implant clearance (K152958). The Implant and Delivery Device were evaluated in a German clinical study 
that evaluated device safety and performance in 30 subjects.   
2. Since clearance was obtained in June 2016, the device has been used in accordance with its cleared 
indications for use and instructions for use in approximately 300 US commercial cases (with over 500 
implants placed, approximately 90% bilateral placement).  These cases have included device usage 
across a spectrum of patients that include both stand alone cases (11%) and cases conducted in 
conjunction with standard of care procedures (89%) for addressing other types of nasal obstruction (i.e., 
septoplasty and/or turbinate reduction procedures). To date, no clinically significant complaints or MDR 
reportable events have been received.  
3. Spirox developed the subject clinical protocol to evaluate device usage in a controlled manner in the US 
and to collect data to support potential regulatory applications and publications regarding device usage.  
a. In the proposed study protocol, the Latera Implant is being used according to its cleared indications 
for use and instructions for use (i.e., to support nasal lateral cartilage).  
b. While the Sponsor believes that this study meets the requirements of an exempt study (i.e., device is 
being used in accordance with its cleared indications for use and instructions for use), Spirox has 
opted to comply with a higher regulatory standard and as such respectfully requests IRB approval to 
conduct this study under the abbreviated IDE requirements. The decision to conduct this protocol as 
an NSR study as opposed to an exempt study affords Spirox with the opportunity to use this data to 
support potential regulatory applications and publications.  For these reasons and those articulated 
below, Spirox does not believe that device usage under the subject study protocol meets the 
requirements of a significant risk study. 
Non-Significant Risk Rationale for Latera Device 
1. While the device is an Implant, it does not present a potential for serious risk to the health, safety, or 
welfare of a subject; 
• 
The Latera Implant is being used according to its cleared indications for use and instructions for use. 
The device was evaluated in a 30 patient clinical study in Germany. Thirty subjects have reached their 
12 month follow up period and 18 subjects have reached the 18 month follow up period; no serious 
risks to the health, safety or welfare of the subjects have been reported. The device has been used in 
approximately 300 commercial cases since June 2016, and no clinically significant complaints or MDR 
reportable events have been received.  
2. The device is not purported or represented to be used for supporting or sustaining human life; 
• 
The Latera Implant is used for supporting nasal lateral cartilage and is not used to support or sustain 
human life. Device usage is optional / elective and may be used to help reduce quality of life 
symptoms associated with nasal obstruction. Nasal obstruction associated with weak lateral 
cartilage or otherwise is not a life threatening disease or condition.  
3. The device is not intended for a use of substantial importance in diagnosing, curing, mitigating, or 
treating disease or otherwise preventing impairment of human health; and, 

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• 
The device is used to support the nasal lateral cartilage and reduce quality of life symptoms 
associated with nasal obstruction, a condition that is not considered life-threatening. Therefore, 
device usage is optional / elective and is not of a substantial importance in treating disease. Several 
other elective options exist for supporting the lateral cartilage. These options range from the use of 
external nasal strips (e.g., over the counter Breathe Right strips) to surgical procedures employing the 
use of autologous and synthetic grafts. Latera is simply one option for supporting the lateral cartilage 
and is not for a use of substantial importance in treating disease (i.e., Latera cartilage support is used 
to reduce quality of life symptoms associated with nasal obstruction, not for a use of substantial 
importance in treating disease or otherwise preventing impairment of human health).  
4. The device does not otherwise present a potential for serious risk to the health, safety or welfare of the 
subject. 
• 
The device has been used in a 30 patient clinical evaluation with up to 18 months of follow up and in 
over approximately 300 commercial cases since June 2016. No reports of a potential for serious risk 
to the health, safety or welfare of any subjects have been noted.