The RhinAer Procedure for Treatment of CHronic RhInitis - A Prospective, MulticeNter Randomized ConTrolled TRial Comparing RhinAer to Sham Control (RHINTRAC)
Phase: NA
Conditions: Chronic Rhinitis
Sponsor: Aerin Medical

 
 
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The RhinAer® Procedure for Treatment of CHronic RhInitis - A 
Prospective, MulticeNter Randomized ConTrolled TRial Comparing 
RhinAer to Sham Control (RHINTRAC) 
Protocol Number: 
CTP1004 
Protocol Date: 
22 May 2020 
Amendment Date: 
03 Mar 2021 
Version: 
E 
Co-Principal Investigators: 
J. Pablo Stolovitzky, MD 
ENT of Georgia North 
1790 Presidential Cir, Suite A 
Snellville, GA 30078 
Phone: 404-297-4230  
email: sto@entofga.com 
 
Mas Takashima, MD 
The Sinus Center at Houston Methodist Hospital 
6550 Fannin Street #1701 
Houston, TX 77030 
Phone: 713-441-1368 
email: mtakashima@houstonmethodist.org 
 
Sponsor: 
Aerin Medical, Inc. 
232 E. Caribbean Drive 
Sunnyvale, CA 94089 
 
Contact: Anais Laborde 
 
Director of Clinical Affairs 
Phone: 650-518-9624 
email: alaborde@aerinmedical.com  
 
 
INVESTIGATOR 
I, the undersigned, certify that I have reviewed this Clinical Investigational Plan and agree to abide by the 
terms of the study described herein and within the Investigator Agreement, Clinical Trial Agreement and 
according to the Declaration of Helsinki and The Belmont Report as well as any conditions imposed by the 
reviewing IRB, U.S. FDA or other regulatory agency. 
Print Name: 
 
Signature: 
 
Date: 
 
 
This protocol contains proprietary and confidential information of Aerin Medical, Inc and should be restricted in its 
distribution to investigators, subinvestigators, and reviewing Institutional Review Boards.  Do not copy, distribute, or 
share with others without prior written authorization from Aerin Medical Inc. 

 
 
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Table of Contents 
Protocol Summary .................................................................................................................... 5 
List of Abbreviations .............................................................................................................. 11 
1.0 Introduction and Background .................................................................................... 13 
2.0 Purpose.......................................................................................................................... 15 
2.1 
Device and Regulatory Status ......................................................................... 15 
2.2 
Indications for Use ........................................................................................... 15 
2.3 
Rationale ........................................................................................................... 15 
3.0 Study Objectives........................................................................................................... 16 
3.1 
Primary Objective ............................................................................................ 16 
3.2 
Secondary Objectives....................................................................................... 16 
3.3 
Safety and Risk Profile .................................................................................... 17 
4.0 Study Plan ..................................................................................................................... 17 
4.1 
Study Design ..................................................................................................... 17 
4.2 
Study Population .............................................................................................. 18 
4.2.1 Inclusion Criteria .....................................................................................18 
4.2.2 Exclusion Criteria ....................................................................................18 
4.3 
Enrollment and Randomization ..................................................................... 19 
4.4 
Blinding ............................................................................................................. 19 
4.5 
Outcome Measures........................................................................................... 20 
4.5.1 Nasal Assessment .....................................................................................20 
4.5.2 Pain – Visual Analog Scale Pain Score ..................................................20 
4.5.3 Total Nasal Symptom Score (TNSS) ......................................................21 
4.5.4 Other Rhinitis Symptoms - Cough and Postnasal Drip .......................21 
4.5.5 Mini Rhinoconjunctivitis Quality of Life Questionnaire 
(MiniRQLQ) .............................................................................................22 
4.5.6 Participant Satisfaction ...........................................................................23 
4.5.7 Change in Amount of PRN Medication/Device Use for Chronic 
Rhinitis Symptoms ...................................................................................23 
4.5.8 Medication and Other Therapies for Symptoms of Chronic 
Rhinitis ......................................................................................................23 
4.5.9 Adverse Events .........................................................................................23 
4.6 
Success/Failure Criteria .................................................................................. 23 
4.6.1 Participant Success ..................................................................................23 
4.6.2 Participant Failure ...................................................................................23 
4.6.3 Study Success ............................................................................................23 
4.7 
Duration of the Study ...................................................................................... 24 
4.8 
Site Staffing and Responsibilities of Study Personnel .................................. 24 
4.9 
Device Description ........................................................................................... 24 
4.10 
Risk/Benefit Analysis ....................................................................................... 27 
4.10.1 Risks ..........................................................................................................27 
4.10.2 Mitigation of Risks ...................................................................................28 
4.10.3 Benefits ......................................................................................................29 
4.10.4 Potential Risks to Participant Confidentiality ......................................29 
4.10.5 Study Justification in Relation to Risk ..................................................30 

 
 
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5.0 Study Schedule and Procedures ................................................................................. 30 
5.1 
Schedule of Events ........................................................................................... 30 
5.2 
Participant Flowchart ...................................................................................... 31 
5.3 
Enrollment and Baseline Assessment ............................................................. 32 
5.4 
Treatment Visit and Procedure ...................................................................... 33 
5.5 
Postprocedure Assessments and Care ............................................................ 35 
5.6 
Follow-up Evaluations and Study Exit .......................................................... 36 
5.7 
Product Handling and Accountability ........................................................... 37 
6.0 Statistical Considerations ............................................................................................ 38 
6.1 
Study Design ..................................................................................................... 38 
6.2 
Study Hypotheses ............................................................................................. 38 
6.3 
Sample Size Estimate ....................................................................................... 38 
6.4 
Timing of Analysis ........................................................................................... 39 
6.5 
Analysis Populations ........................................................................................ 39 
6.6 
Missing Data ..................................................................................................... 40 
6.7 
Pooling ............................................................................................................... 40 
6.8 
Participant Disposition .................................................................................... 40 
6.9 
Demographics and Characteristics ................................................................ 40 
6.10 
Primary Endpoint Analysis ............................................................................. 41 
6.11 
Secondary Endpoints Analysis........................................................................ 41 
6.12 
Other Outcome Measures Analyses ............................................................... 41 
6.13 
Safety Analysis ................................................................................................. 43 
6.14 
Extension Phase Analysis ................................................................................ 43 
6.15 
Standard Methods of Report .......................................................................... 43 
7.0 Adverse Events and Product Complaints .................................................................. 43 
7.1 
Adverse Events ................................................................................................. 43 
7.1.1 Definitions .................................................................................................43 
7.1.2 Documentation and Reporting of Adverse Events ................................45 
7.2 
Product Complaints ......................................................................................... 46 
7.2.1 Definitions .................................................................................................46 
7.2.2 Documentation and Reporting of Complaints ......................................47 
8.0 Study Administration .................................................................................................. 47 
8.1 
Investigator Training ....................................................................................... 47 
8.2 
Study Monitoring ............................................................................................. 47 
8.3 
Documentation of Study Findings .................................................................. 48 
8.3.1 Data Management ....................................................................................48 
8.3.2 Case Report Forms ..................................................................................48 
8.3.3 Investigator Responsibilities, Records, and Reports ............................49 
8.3.4 Retention of Study Records.....................................................................51 
8.3.5 Data Quality Assurance ...........................................................................51 
8.3.6 Confidentiality ..........................................................................................51 
8.3.7 Publication Policies ..................................................................................52 
8.4 
Early Termination ........................................................................................... 52 
9.0 Ethics ............................................................................................................................. 53 
9.1 
Institutional Review Board ............................................................................. 53 

 
 
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9.2 
Ethical Conduct of the Study .......................................................................... 53 
9.3 
Participant Privacy .......................................................................................... 53 
9.4 
Participant Reimbursement ............................................................................ 53 
9.5 
Participant Withdrawal................................................................................... 54 
9.6 
Protocol Modifications..................................................................................... 54 
9.7 
Protocol Adherence and Deviations ............................................................... 54 
10.0 References ..................................................................................................................... 55 

 
 
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Protocol Summary 
Title of Study: 
The RhinAer® Procedure for Treatment of CHronic RhInitis - A 
Prospective, MulticeNter Randomized ConTrolled TRial Comparing 
RhinAer to Sham Control (RHINTRAC) 
Purpose: 
The purpose of this study is to compare the RhinAer procedure to treat 
tissue in the posterior nasal nerve area to improve symptoms in adults 
diagnosed with chronic rhinitis with a sham procedure that duplicates 
the actual procedure as closely as possible absent the delivery of 
radiofrequency (RF) energy to the nasal tissue. 
Indications for 
Use:  
The RhinAer Stylus is indicated for use in otorhinolaryngology (ENT) 
surgery for the destruction of soft tissue in the nasal airway, including in 
posterior nasal nerve regions in patients with chronic rhinitis.   
The Aerin Console is an electrosurgical system intended to generate 
radiofrequency electrical current for the use of an Aerin Medical Stylus.  
The Aerin Console is indicated for use in small clinic, office, or hospital 
environments. 
RhinAer 
Treatment: 
The RhinAer procedure will be performed in the study clinic using the 
RhinAer Stylus and Aerin Console. The RhinAer Stylus is a disposable 
handheld device capable of delivering bipolar radiofrequency energy to 
tissue when connected to the Aerin Console radiofrequency generating 
device. Participants will have the portion of the nasal cavity mucosa 
overlying the region of the posterior nasal nerve (the posterior middle 
meatus and posterior inferior turbinate) in both nostrils treated during a 
single study procedure session. Each nostril will be treated at 1, 2, 3, 4 
or 5 nonoverlapping positions depending on the size of the target 
treatment area. Treatment settings to be used are temperature 60 °C, 
power 4 watts, treatment time 12 seconds, and cooling time 0 seconds. 
Control 
Treatment: 
The control treatment will be performed in the study clinic using the 
RhinAer Stylus while audible sounds that accurately simulate the Aerin 
Console's active treatment are produced even though RF energy is not being 
generated or delivered. All other aspects of the procedure will be the same 
as used for the active treatment, including administration of anesthetic 
agent(s). 
Study Design: 
The study is designed as a multicenter (up to 20 sites), prospective, 
randomized, controlled superiority trial with a one-way crossover 
component available to participants randomized to the control 
procedure. A 2:1 site-stratified randomization will be used to allocate 
participants to either the RhinAer procedure or  treatment with the sham 
(control) procedure to provide up to 120 total participants in the 
following groups: 

 
 
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• 80 active treatment receiving the RhinAer procedure 
• 40 inactive treatment receiving the sham procedure 
All participants will be evaluated prior to treatment and following 
treatment at week 4 (1 month) and week 13 (3 months). The 3-month 
evaluation will be used for the primary endpoint analysis. 
The study will have an extended follow-up phase with evaluations 
conducted at 6 months (26 weeks), 12 months (52 weeks) and 24 months 
(104 weeks) to provide additional information on longer-term efficacy 
and duration of treatment effect. 
Participants receiving the sham procedure may elect to crossover and 
receive the active RhinAer procedure within 30 days after the 3- or 6-
month evaluation provided they still meet all original eligibility criteria. 
New baseline information will be collected prior to the RhinAer 
procedure.  Continued follow-up will be conducted at 1, 3, 6, 12, and 24 
months after the RhinAer procedure. 
Participants that received the sham procedure who do not crossover or 
no longer meet all eligibility criteria may elect to exit from the study 
following the 3- or 6-month evaluation. 
Study 
Objective: 
The primary objective is to assess the performance of the RhinAer 
procedure compared to a sham procedure with respect to individual 
participant success rates when used as a treatment for chronic rhinitis. A 
secondary objective is evaluation of treatment effect duration through an 
extended follow-up to 2 years. 
Individual participant success (responder) is defined as at least 30% 
improvement (decrease) in the 24-hour reflective Total Nasal Symptom 
Score (rTNSS). 
Primary Study 
Hypothesis: 
The proportion of participants receiving the RhinAer procedure with a 
successful outcome (responders) will exceed the proportion of 
participants receiving the sham procedure with a successful outcome 
(responders) at 3 months posttreatment. 
Primary 
Endpoint: 
The primary endpoint is the responder rate at 3 months after the 
procedure for the randomized participants.  
Secondary 
Endpoints: 
• Mean change in rTNSS from baseline to 3 months after the 
procedure.  
• Frequency of device-related and procedure-related serious adverse 
events through the 3-month evaluation. 
Other 
Effectiveness 
and Safety 
Measures: 
Adverse events - Incidence (type and category) of adverse events overall 
and by follow-up interval. 
Nasal Assessment - The target posterior nasal nerve area within each 
nostril will be visually assessed at baseline, just prior to treatment, 

 
 
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immediately after treatment, at 1 month, 3 months, and 6 months after 
the procedure. The use of an endoscope for visual assessment is required. 
Representative still photographs or video of each nostril will be captured 
for each assessment. 
Visual analog scale (VAS) for pain - perception of pain associated with 
the procedure on a 0 to 100 mm scale with 0 indicating no pain and 100 
indicating the worst pain ever assessed posttreatment, 1 month, and 3 
months. 
rTNSS:  
• Mean and mean change from baseline at the 3-, 6-, 12-, and 24-
month follow-up evaluations. 
• rTNSS Individual Nasal Symptom Scores (rhinorrhea, nasal 
congestion, nasal itching, and sneezing) at baseline and the 3-, 6-, 
12-, and 24-month follow-up evaluations. 
• Proportion of responders based on improvement in rTNSS at the 3-, 
6-, 12-, and 24-month follow-up evaluations. 
Other rhinitis symptoms - current symptoms of cough and postnasal drip 
or excess mucous in the throat, rated on a 0 to 3 scale from ‘No 
symptoms’ to ‘Severe symptoms’, assessed at baseline and the 3-, 6-, 
12-, and 24-month follow-up evaluations. 
MiniRQLQ: 
• MiniRQLQ mean and change from baseline at the 3-, 6-, 12-, and 
24-month follow-up evaluation. 
• MiniRQLQ domain scores (activity limitations, practical problems, 
nose symptoms, eye symptoms, and other symptoms) at baseline 
and the 3-, 6-, 12-, and 24-month follow-up evaluations. 
Participant satisfaction assessment - Five-question self-reported survey 
of satisfaction with the procedure and recommendation to others 
administered at the 3-, 6-, 12-, and 24-month, follow-up evaluations. 
Change in amount of “as needed” medication/device use for chronic 
rhinitis symptoms - Self-reported assessment of an increase, no change, 
or decrease in medications and/or devices being used for treatment of  
symptoms compared to use prior to the procedure administered at the 3-, 
6-, 12-, and 24-month follow-up evaluations. 
Medications - Medications associated with relief or treatment of chronic 
rhinitis symptoms will be documented at baseline and updated as 
necessary at each evaluation. In addition, medications associated with 
treatment of adverse events will be documented. 

 
 
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Length of 
Study: 
The primary endpoint will be evaluated at 3 months. In addition, 
evaluations at 6, 12, and 24 months after treatment will extend follow-
up to 2 years for evaluation of longer-term efficacy. Participants 
receiving the sham procedure and meeting the original eligibility 
requirements may elect to crossover and receive the active RhinAer 
procedure within 30 days after the 3- or 6-month evaluation with 
continued follow-up for 24 more months for a total of up to 31 months 
of follow-up. Enrollment is anticipated to be completed within 12 
months. Therefore, total study duration is anticipated to be 
approximately 43 months. 
Study Centers: 
up to 20  
 
Participants: 
120 
 
Inclusion 
Criteria: 
1. Age 18 to 85 years (inclusively). 
2. Willing and able to provide informed consent. 
3. Willing and able to comply with the subject-specific requirements 
outlined in the Study Protocol. 
4. Seeking treatment for chronic rhinitis symptoms of at least 6 months 
duration and willing to undergo an office-based procedure. 
5. Moderate to severe symptoms of rhinorrhea (rTNSS rating of 2 or 
3 for rhinorrhea). 
6. Mild to severe symptoms of nasal congestion (rTNSS rating of 1, 2 
or 3 for congestion). 
7. rTNSS ≥ 6. 
Exclusion 
Criteria: 
1. Anatomic obstructions that in the investigator’s opinion limit access 
to the posterior nasal passage.  
2. Altered anatomy of the posterior nose as a result of prior sinus or 
nasal surgery or injury. 
3. Active nasal or sinus infection. 
4. History of significant dry eye. 
5. History of any of the following: chronic epistaxis, documented 
episodes of significant nose bleeds in the past 3 months, rhinitis 
medicamentosa, head or neck irradiation. 
6. Have rhinitis symptoms only on a seasonal basis due to allergies. 

 
 
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7. Known or suspected allergies or contraindications to the anesthetic 
agents and/or antibiotic medications to be used during the study 
procedure session. 
8. Known or suspected to be pregnant or is lactating. 
9. Participating in another clinical research study. 
10. Has any condition that predisposes to excessive bleeding. 
11. Is taking anticoagulants (eg, warfarin, Plavix) or 325 mg aspirin that 
cannot be discontinued before the procedure. 
12. Has previous procedure or surgery for chronic rhinitis. 
13. Other medical conditions which in the opinion of the investigator 
would predispose the subject to poor wound healing, increased 
surgical risk, or poor compliance with the requirements of the study. 
 
 
 

 
 
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Schedule of Events 
 
 
 
Screening 
Treatment 
Follow-up  
(office) 
Extended follow-
up (remote) 
  Procedure 
    Immediate 
Postprocedure 
  1 Month 
(4 weeks) 
  3 Months1  
  (13 weeks) 
  6 Months1 
  (26 weeks) 
 12 Months 
 (52 weeks) 
 24 Months 
 (104 weeks) 
Window (days) 
(-30) 
(0) 
(0) 
(± 7) 
(± 14) 
(± 30) 
(± 30) 
(± 30) 
Activity / Assessment 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
Nasal assessment (physical, endoscopic) 
X 
X2 
X 
X 
X 
X 
 
 
Current medication use (study relevant) 
X 
X2 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
 
 
 
 
 
 
 
VAS nasal pain  
 
 
X 
X 
X 
 
 
 
Rhinitis symptoms (rTNSS, cough, and 
postnasal drip)  
X 
X2 
 
 
X 
X 
X 
X 
MiniRQLQ 
X 
X2 
 
 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
 
X 
X 
X 
X 
Adverse Events 
X 
X2 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
1Control participants eligible to crossover and receive RhinAer procedure. 
 
 
 
2Repeat only on day of treatment if screening was conducted after 72 hours day of procedure. 

 
 
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List of Abbreviations 
AADE – Anticipated Adverse Device Effect 
ADE – Adverse Device Effect 
AE – Adverse Event 
ANOVA – analysis of variance 
AR – allergic rhinitis 
BMI – Body Mass Index 
CONSORT – Consolidated Standards of Reporting Trials 
CRF (eCRF) – Case Report Form (electronic Case Report Form) 
CTA – Clinical Trial Agreement 
EDC – Electronic data capture 
ENT – Ear, Nose, Throat; medical field of otorhinolaryngology (otolaryngology) 
FDA – Food and Drug Administration (US) 
FWA – Federalwide Assurance for the Protection of Human Subjects 
GCP – Good Clinical Practice 
HIPAA – Health Insurance Portability and Accountability Act 
ICH – International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICMJE – International Committee of Medical Journal Editors 
IRB – Institutional Review Board 
ISO – International Organization for Standardization 
ITT – Intent-To-Treat 
MCID – minimal clinically important difference 
MiniRQLQ – Mini Rhinoconjunctivitis Quality of Life Questionnaire  
NAR – nonallergic rhinitis 

 
 
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PNN – posterior nasal nerve 
PRN – Pro Re Nata (as needed or as required) 
RF – Radiofrequency 
RFTR – Radiofrequency turbinate reduction 
rTNSS – Total Nasal Symptom Score (r, reflective) 
SADE – Serious Adverse Device Effect 
SAE – Serious Adverse Event 
SD – standard deviation 
UADE (USADE) – Unanticipated (Serious) Adverse Device Effect 
VAS – Visual Analog Scale 
 

 
 
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1.0 
Introduction and Background 
Rhinitis is a condition in which the membrane lining the nasal cavity becomes irritated 
and swollen. Patients typically present with complaints of congestion, runny nose, 
sneezing, nasal itching, irritated throat, and postnasal discharge. The 2 major 
classifications of rhinitis are allergic rhinitis (AR) and nonallergic rhinitis (NAR). AR 
may be caused by allergens such as pollen, pet dander, mold or dust. NAR may result 
from triggers that include chemicals, irritants, and medications.1 
Chronic rhinitis may significantly impact a patient’s quality of life by causing fatigue, 
headache, and sleep disturbance, resulting in cognitive impairment and diminished 
productivity and thereby posing both a personal and financial burden.2 
The nasal cavity is covered with an epithelial lining made of cells which interact to 
serve appropriate functions in the nasal environment.3 Cells located in the epithelial 
lining include ciliated cells, goblet cells and seromucous glands. The goblet cell 
produces a carbohydrate called mucin which attracts water and forms a gelatin-like 
substance better known as mucus.3,4 The goblet cell is the most prominent mucus 
producing cell in the nasal membrane and, together with the seromucous glands, works 
to provide mucus to the nasal mucosal surface. The purpose of mucus is to protect the 
body from substances that can enter through the nasal cavity. Secretion is stimulated 
by dust or foreign substances that enter the nasal passage. Mucus is cleared by 
movement of the cilia and disposed to the stomach.4 Regulation of the seromucous 
glands and mucosal blood supply occurs through parasympathetic and adrenergic 
stimulation via the vidian nerve, posterior nasal nerves and other nerves. In some 
situations, the mucosa may become hyperresponsive to stimuli and produce excess 
mucus, resulting in rhinorrhea or postnasal discharge. 
Patients presenting with runny or congested nose, watery eyes, irritated throat and/or 
sneezing symptoms are evaluated to understand the types of triggers that may prompt 
the symptoms experienced. Understanding the patient’s respiratory irritants may help 
differentiate between allergic or nonallergic responses.2,5,6 Physicians can observe the 
nasal structures by transnasal endoscopy to rule out anatomic conditions mimicking 
rhinitis. Common anatomical obstructions that may cause rhinitis-like symptoms are 
nasal polyps, deviated septum, foreign bodies, nasal tumors and turbinate hypertropy.1,2  
Treatment of these anatomical causes, if present, may relieve rhinitis symptoms. The 
most common methods to determine allergy sensitivity are percutaneous skin testing 
and the allergen-specific immunoglobulin E (IgE) antibody testing. These tests can 
identify allergens the patient should avoid. However, if an allergic cause is eliminated 
through this testing, a diagnosis of nonallergic rhinitis could be made.1,2 
Treatment to reduce symptoms may include nasal irrigation (nasal lavage) multiple 
times a day with a saline rinse, use of over-the-counter oral or nasal antihistamines 
and/or corticosteroid sprays, and allergen immunotherapy in AR patients. Patients with 
nonallergic rhinitis are less likely to respond to oral antihistamines, but may find their 
symptoms relieved with intranasal antihistamine, corticosteroid or anticholinergic 
sprays. Patients whose symptoms are not adequately relieved with conservative 
treatment often seek treatment to alleviate symptoms and may be candidates for nasal 

 
 
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surgery. Vidian neurectomy is a surgical option to relieve chronic rhinitis symptoms as 
the vidian nerve supplies autonomic input to the nasal mucosa (as well as the palate 
and the lacrimal gland). While this surgery has been performed for over 50 years, it is 
controversial since access to the nerve can be technically difficult and complications 
with numerous surrounding important structures can occur.7,8 Common procedural side 
effects include dry eyes, nasal dryness or crusting and mild pain. More significant risks 
may include hemorrhage, vision loss and palate/lip/cheek numbness. In addition, 
improvement in symptoms is often unpredictable.7 An alternative neurectomy target is 
the posterior nasal nerve (PNN). The advantage of the PNN over the vidian nerve is its 
more limited innervation and activity on the nasal mucosa and its physical distance 
from other major nerve structures. As a result, complications associated with PNN 
surgery are less significant and occur less frequently than those described for vidian 
neurectomy,7 while still providing significant improvement in quality of life.9 A recent 
development is use of a cryosurgical probe to ablate PNN tissue.10 Significant 
improvement from baseline in Total Nasal Symptom Score (TNSS) using this 
cryosurgical probe was observed. 
Radiofrequency (RF) energy has been used for decades in the fields of 
otorhinolaryngology, neurosurgery, cardiology, urology and general surgery. ENT 
surgeons currently use radiofrequency energy in numerous nasal therapies, including 
radiofrequency turbinate reduction (RFTR), which is a minimally invasive surgical 
option that can reduce tissue volume in a precise, targeted manner. There have been 
multiple studies analyzing the safety and outcomes of using radiofrequency energy in 
the RFTR procedure.11 The technique is well tolerated and effective. Numerous studies 
have also demonstrated that radiofrequency tissue therapy in the nasal passage can be 
safe and effective in improving nasal obstruction and in preserving nasal function.12 
Aerin Medical’s radiofrequency system using the Vivaer® ARC Stylus has been 
investigated and shown effective in treatment of nasal airway obstruction.13 
Aerin Medical previously conducted a small feasibility study (TP220) using the Aerin 
Medical radiofrequency system to treat subjects with chronic rhinitis. The InSeca® 
Stylus was used to apply radiofrequency energy to the inferior turbinate in the PNN 
area. At 6-months post procedure, 73% of subjects showed improvement in their Sino-
Nasal Outcomes (SNOT-22) score. There were no device-related or procedure-related 
serious adverse events. 
The feasibility study was followed by a prospective, nonrandomized multicenter study 
(TP668) with 50 participants that supported regulatory clearance of the RhinAer Stylus 
for treating rhinitis by targeting treatment to the portion of the inferior turbinate mucosa 
overlying the region of the PNN. The mean reflective Total Nasal Symptom Score 
(rTNSS) at baseline was 8.5 (SD 1.8) and improved to 3.4 (SD 2.3) at the 12-week 
primary endpoint (5.1-point or 59.2% improvement). The responder rate for at least a 
1-point improvement in rTNSS at 12 weeks was 94%. Responder rates based on at least 
2-, 3- (~30%), and 4-point improvements in rTNSS were 92%, 88%, and 69%. Patient 
reported satisfaction with the procedure and quality of life improvement were high. No 
serious adverse events related to the device were observed and the limited number of 
adverse events possibly associated with the procedure or device were relatively mild, 

 
 
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transient, and not unexpected for this type of procedure. Together, the safety and 
efficacy results demonstrated the benefits of treating the PNN area of the nasal 
passageway with RF using the Aerin Medical procedure for relief of chronic rhinitis. 
The current study is proposed to provide additional evidence for the effectiveness of 
the RF procedure when compared to a sham procedure through a randomized clinical 
trial. 
2.0 
Purpose 
The purpose of this study is to compare the RhinAer procedure to treat tissue in the 
posterior nasal nerve area to improve symptoms in adults diagnosed with chronic 
rhinitis with a sham procedure that duplicates the actual procedure as closely as 
possible absent the delivery of radiofrequency energy to the nasal. 
2.1 Device and Regulatory Status 
The RhinAer procedure will be performed in the study clinic using the RhinAer 
Stylus and Aerin Console. The RhinAer Stylus is a disposable handheld device 
capable of delivering bipolar radiofrequency energy to tissue when connected to the 
Aerin Console radiofrequency generating device. 
The RhinAer Stylus was cleared for use in the USA by the FDA under 510(k) 
K192471 and the Aerin Console was cleared under 510(k) K162810. 
2.2 Indications for Use 
The RhinAer Stylus is indicated for use in otorhinolaryngology (ENT) surgery for 
the destruction of soft tissue in the nasal airway, including in posterior nasal nerve 
regions in patients with chronic rhinitis. 
The Aerin Console is an electrosurgical system intended to generate radiofrequency 
electrical current for the use of an Aerin Medical Stylus. The Aerin Console is 
indicated for use in small clinic, office or hospital environments. 
2.3 Rationale 
Patients suffering from symptoms attributed to chronic rhinitis have treatment 
options ranging from medications to surgical procedures that have varying degrees 
of effectiveness, discomfort, and potential complications. There remains a significant 
need for a simple, safe, nonsurgical, minimally invasive treatment that can provide 
sustained relief for patients suffering with symptoms of chronic rhinitis. The RhinAer 
procedure using RF technology has been shown to be safe, effective and durable in a 
single-arm trial comparing pretreatment condition with posttreatment condition. This 
study is being undertaken to provide additional evidence of the effectiveness of the 
procedure using the randomized, controlled trial, “gold standard” study design. 

 
 
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3.0 
Study Objectives 
3.1 Primary Objective 
The primary objective is to assess the performance of the RhinAer procedure 
compared to a sham procedure with respect to individual participant success rates 
when used as a treatment for chronic rhinitis. 
Individual participant success (responder) is defined as at least 30% improvement 
(decrease) in the 24-hour reflective Total Nasal Symptom Score (rTNSS). 
The primary objective will be assessed through evaluation of the primary endpoint 
defined as comparison of the RhinAer procedure and sham procedure success rates 
at 3 months post procedure. 
3.2 Secondary Objectives 
Additional objectives include assessment and comparison of secondary endpoints and 
informational outcome measures between the groups receiving the RhinAer 
procedure and the sham control treatment. 
Secondary endpoints are: 
• Mean change in the rTNSS from baseline at 3 months. 
• Frequency of device-related and procedure-related serious adverse events 
through the 3-month evaluation. 
Informational outcomes include: 
• Adverse events - Incidence (type and category) of adverse events overall 
and by follow-up interval. 
• Nasal Assessment - The target posterior nasal nerve area within each nostril 
will be visually assessed at baseline and following the treatment procedure 
at all evaluations. The use of an endoscope for visual assessment is required.  
Representative still photographs or video of each nostril will be captured at 
each visit. 
• Visual analog scale (VAS) for pain - perception of pain associated with the 
procedure on a 0 to 100 mm scale with 0 indicating no pain and 100 
indicating the worst pain ever posttreatment through 3 months. 
• rTNSS:  
o rTNSS mean and change from baseline at the 3-, 6-, 12-, and 24-month 
follow-up evaluations. 
o rTNSS Individual Nasal Symptom Scores (rhinorrhea, nasal 
congestion, nasal itching, and sneezing) at baseline and the 3-, 6-, 12-, 
and 24-month follow-up evaluations. 
o Proportion of responders based on improvement in rTNSS at the 3-, 
6-, 12-, and 24-month follow-up evaluations. 

 
 
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• Other rhinitis symptoms: current symptoms of cough and postnasal drip or 
excess mucous in the throat, rated on a 0 to 3 scale from ‘No symptoms’ to 
‘Severe symptoms’, assessed at baseline and the 3-, 6-, 12-, and 24-month 
follow-up evaluations. 
• MiniRQLQ:  
o MiniRQLQ mean and change from baseline at the 3-, 6-, 12-, and 24-
month follow-up evaluation. 
o MiniRQLQ domain scores (activity limitations, practical problems, 
nose symptoms, eye symptoms, and other symptoms) at baseline and 
the 3-, 6-, 12-, and 24-month follow-up evaluations. 
• Participant satisfaction assessment - Five-question self-reported survey of 
satisfaction with the procedure and recommendation to others summarized 
by question at the 3-, 6-, 12-, and 24-month follow-up evaluations. 
• Change in amount of PRN medication/device use for chronic rhinitis 
symptoms - Self-reported assessment of an increase, no change, or decrease 
in medications being used for treatment of symptoms compared to use prior 
to the procedure summarized by category at the 3-, 6-, 12-, and 24-month 
follow-up evaluations. 
• Medications - Medications associated with relief or treatment of chronic 
rhinitis symptoms will be documented at baseline and updated as necessary 
at each evaluation.  In addition, medications associated with treatment of 
adverse events will be documented. 
3.3 Safety and Risk Profile 
The safety and risk profile of the RhinAer procedure relative to the sham control 
procedure will be evaluated with respect to overall incidence of adverse events and 
treatment-related adverse events. 
4.0 
Study Plan 
4.1 Study Design 
The study is designed as a multicenter (up to 20 sites), prospective, randomized, 
controlled superiority trial with a one-way crossover component available to 
participants randomized to the control procedure A 2:1 site-stratified randomization 
will be used to allocate participants with chronic rhinitis to either the RhinAer 
procedure or  treatment with the sham (control) procedure to provide up to 120 total 
participants: 
• 80 active treatment (RhinAer procedure) 
• 40 sham treatment control. 
All participants will be evaluated prior to treatment and following treatment at week 
4 (1 month) and week 13 (3 months). The 3-month evaluation will be used for the 
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The study will have an extended follow-up phase with evaluations conducted at 6 
months (26 weeks), 12 months (52 weeks) and 24 months (104 weeks) to provide 
additional information on longer-term efficacy and duration of treatment effect. 
The study will have an additional evaluation at 3 and 6 months at which time eligible 
sham control participants will be offered the opportunity to cross over and receive 
the RhinAer procedure. Extended follow-up will be conducted at 1, 3, 6 12 and 24 
months to provide additional information on longer-term safety and duration of 
treatment effect. 
4.2 Study Population 
The target population for this study is adults who have exhibited symptoms of chronic 
rhinitis, such as congestion, rhinorrhea, sneezing, and itching, that may be caused by 
nonallergic or allergic triggers for at least 6 months. Patients with symptoms due only 
to seasonal allergies are to be excluded. This study requires significant symptoms 
demonstrated by an rTNSS ≥ 6, which includes moderate to severe symptoms of 
rhinorrhea and mild to severe symptoms of nasal congestion. 
Patients who have anatomic obstructions that may limit access to the target treatment 
area or have altered posterior nasal anatomy due to prior surgery or injury are 
excluded from participation. 
Patients must meet all inclusion and exclusion criteria listed below for participation 
in the study. 
4.2.1 Inclusion Criteria 
1. Age 18 to 85 years (inclusively). 
2. Willing and able to provide informed consent. 
3. Willing and able to comply with the participant-specific requirements 
outlined in the Study Protocol. 
4. Seeking treatment for chronic rhinitis symptoms of at least 6 months 
duration and willing to undergo an office-based procedure. 
5. Moderate to severe symptoms of rhinorrhea (rTNSS rating of 2 or 3 for 
rhinorrhea). 
6. Mild to severe symptoms of nasal congestion (rTNSS rating of 1, 2 or 3 for 
congestion). 
7. rTNSS ≥ 6. 
4.2.2 Exclusion Criteria 
1. Anatomic obstructions that in the investigator’s opinion limit access to the 
posterior nasal passage.  
2. Altered anatomy of the posterior nose as a result of prior sinus or nasal 
surgery or injury. 
3. Active nasal or sinus infection. 

 
 
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4. History of significant dry eye. 
5. History of any of the following: chronic epistaxis, documented episodes of 
significant nose bleeds in the past 3 months, rhinitis medicamentosa, head 
or neck irradiation. 
6. Have rhinitis symptoms only on a seasonal basis due to allergies. 
7. Known or suspected allergies or contraindications to the anesthetic agents 
and/or antibiotic medications to be used during the study procedure session. 
8. Known or suspected to be pregnant or is lactating. 
9. Participating in another clinical research study. 
10. Is taking anticoagulants (eg, warfarin, Plavix) or 325 mg aspirin that cannot 
be discontinued before the procedure. 
11. Has previous procedure or surgery for chronic rhinitis (eg, cryosurgical 
denervation) within 12 months. 
12. Other medical conditions which in the opinion of the investigator would 
predispose the subject to poor wound healing, increased surgical risk, or 
poor compliance with the requirements of the study. 
4.3 Enrollment and Randomization 
Patients diagnosed with chronic rhinitis and meeting all eligibility criteria may be 
enrolled in the study. Randomization should occur just prior to the treatment 
procedure allowing sufficient time to prepare the required treatment. The randomized 
treatment assignment will be determined using a web-based service. Once the 
baseline assessments have been completed, results must be entered into the electronic 
data capture (EDC) system before the system will randomize the participant to a 
treatment group. Participants will be assigned to a treatment group (RhinAer 
procedure or sham control) in a 2:1 allocation, using the computer-generated 
randomization scheme stratified by site. To help assure balance in treatment 
assignment within sites a block randomization scheme will be implemented. Sites 
will be trained at site initiation to follow detailed randomization instructions to assure 
strict adherence to the randomization process. 
4.4 Blinding 
It will not be possible to blind the investigator administering the treatment because 
of obvious differences in the actual application of the RF energy versus the sham 
control. However, every effort should be made to keep the participant blinded as to 
the treatment received. Steps to help maintain blinding include: 
• Following the same preparation procedures for all cases, including administration 
of anesthetics (topical and local). 
• Application of the RhinAer Stylus in the same manner (pressure, locations, 
timing) for both the active and sham procedures. 

 
 
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• Simulation of RF energy being applied by having the Aerin Console appear to 
make audible sounds even though RF energy is not being generated for the sham 
procedure. 
• Use of a blinded evaluator (nontreating physician) to conduct the follow-up visit 
nasal assessment when feasible; however, this is not required. Medical personnel 
who are unaware of the treatment received are also preferred for overseeing and 
coordinating the collection of the participant reported outcome measures during 
the follow-up evaluations. At a minimum, the treating physician should not be 
present when the participant reported outcomes are being collected. Site training 
will include the importance of maintaining the blinded nature of the study and 
caution against inadvertent revelation of the treatment assignment by study 
personnel. 
4.5 Outcome Measures 
4.5.1 Nasal Assessment 
The target posterior nasal nerve area within each nostril will be visually 
assessed at baseline (pretreatment), immediately following the treatment 
procedure, and at the 1-month, 3-month, and 6-month evaluations. The use of 
an endoscope for visual assessment is required. Observations are categorized as 
not present, mild, moderate, or severe. Representative still photographs or video 
of each nostril will be captured at each visit. 
Assessments include: 
• Significant dry eye (yes/no) 
• Bruising around orbital area 
• Soreness, pain 
• Numbness 
Endoscope required: 
• Inflammation / generalized redness 
• Swelling, edema  
• Bleeding at anesthetic injection site (not requiring physician 
intervention) 
• Bleeding at treatment site (not requiring physician intervention) 
• Nasal obstruction from tissue edema 
• Disruption of mucosal flow / crusting. 
4.5.2 Pain – Visual Analog Scale Pain Score 
A horizontal 100 mm VAS14 anchored on the left with the words “No Pain” and 
on the right with the words “Worst Pain Imaginable”, will be used to measure 
nasal pain associated with the procedure. Scores are obtained by measuring the 

 
 
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distance in millimeters from the left origin of the line (0) to the point indicated 
with a slash placed by the participant to indicate their current level of pain in 
and around the nose. 
4.5.3 Total Nasal Symptom Score (TNSS) 
The TNSS is an instrument used to collect patient self-rated severity of nasal 
symptoms originally comprised of 3 symptoms (nasal obstruction, 
itching/sneezing and secretion/runny nose)15 that has been widely adapted to 
include 4 nasal symptoms: rhinorrhea, nasal congestion, nasal itching, and 
sneezing. The FDA cites this as a preferred measure of efficacy in trials of drug 
treatments for allergic rhinitis16 and nonallergic rhinitis.17 The TNSS requires 
the patient to rate 4 nasal symptoms (rhinorrhea, nasal congestion, nasal itching 
and sneezing) on the following 4-point scale: 
• 0 = absent symptoms (no sign/symptom is evident) 
• 1 = mild symptoms (sign/symptom present, but minimal awareness; 
easily tolerated) 
• 2 = moderate symptoms (definite awareness of sign/symptom that is 
bothersome but tolerable) 
• 3 = severe symptoms (sign/symptom that is hard to tolerate; causes 
interference with activities of daily living and/or sleeping). 
The total score is the sum of the 4 nasal symptom scores with a maximum TNSS 
of 12 indicating the most severe symptoms. 
The minimal clinically important difference (MCID) for change in mean TNSS 
derived from anchor-based methodologies has been shown to be 0.23 - 0.28 
units and by distribution-based methodology the MCID was determined to be 
0.59 units.18 A less rigorous expert panel-based estimate of the MCID was 30% 
of the maximum score of 12, which is 3.6 units.19 The evidence-based 
thresholds for MCID have been recommended to supersede the panel-based 
method.20,21 
The 24-hour reflective TNSS (rTNSS) will be used in this study. Participants 
will be asked to self-evaluate their symptom severity over the preceding 24 
hours.  
Treatment Responder based on rTNSS improvement 
Individual participant success (responder) is defined as at least 30% 
improvement (decrease) in the rTNSS from baseline. 
4.5.4 Other Rhinitis Symptoms - Cough and Postnasal Drip 
Self-reported assessment of current problems with cough and postnasal drip or 
excess mucous in the throat rated on the same 4-point scale used for symptoms 
comprising the rTNSS: 
• 0 = absent symptoms (no sign/symptom is evident) 

 
 
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• 1 = mild symptoms (sign/symptom present, but minimal awareness; 
easily tolerated) 
• 2 = moderate symptoms (definite awareness of sign/symptom that is 
bothersome but tolerable) 
• 3 = severe symptoms (sign/symptom that is hard to tolerate; causes 
interference with activities of daily living and/or sleeping). 
4.5.5 Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) 
The RQLQ is a well-established, validated, and the most frequently used 
rhinoconjuctivitis disease-specific instrument.22 The original RQLQ consisted 
of 28 questions across 7 domains and included ratings of 3 activities selected 
by the patient.23 The validated standardized version (RQLQ(S)) uses 
standardized activity questions, which facilitates ease of administration.24 The 
MiniRQLQ, to be used in this study, was developed and validated to further 
facilitate ease of use and efficiency by reducing the number of questions to 14.25 
The RQLQ(S) and the MiniRQLQ were found to be the best tests with optimal 
discriminant validity and responsiveness for measurement of health-related 
quality of life in AR patients.26 While much of the development and validation 
of the RQLQ instruments have occurred in AR patients, the MiniRQLQ has 
also been validated for NAR patients.27 
The instrument consists of 14 questions across 5 domains (activity limitations 
(n=3), practical problems (n=2), nose symptoms (n=3), eye symptoms (n=3), 
and other symptoms (n=3)). Responses are based on a 1-week recall and 
provided on a 7-point scale: 
• 0 = not troubled 
• 1 = hardly troubled at all 
• 2 = somewhat troubled 
• 3 = moderately troubled 
• 4 = quite a bit troubled 
• 5 = very troubled 
• 6 = extremely troubled. 
The total or overall MiniRQLQ score is the mean of the 14 responses and the 
domain scores are the mean of the questions in each domain. 
The generally accepted MCID for the overall RQLQ(S) and each individual 
domain is 0.522,24,28,29 and has also been reported as ≥ 0.62.30 The developers of 
the RQLQ instruments reported that the MCID for the MiniRQLQ was slightly 
higher (0.7) than for the RQLQ(S).25 Another study using a combination of both 
anchor-based and distribution-based methods determined the MCID for the 
MiniRQLQ to be 0.42 (95% confidence interval 0.30 - 0.51).31 

 
 
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Also noteworthy for this sham-controlled study is a 1-point placebo 
improvement has been reported from a randomized clinical trial.32 
4.5.6 Participant Satisfaction 
Five-question self-reported survey using a 5-point scale to assess tolerability of 
the procedure, ease of recovery, change in drainage/rhinorrhea/runny nose 
symptoms, overall satisfaction with the procedure, and recommendation to 
others  
4.5.7 Change in Amount of PRN Medication/Device Use for Chronic Rhinitis 
Symptoms  
Self-reported assessment of an increase or decrease from baseline in as needed 
medications and/or devices used for treatment of nasal symptoms following the 
procedure.  
4.5.8 Medication and Other Therapies for Symptoms of Chronic Rhinitis 
The current use of medication, devices or other therapies for symptoms of 
chronic rhinitis, medication name, frequency, and dose will be recorded at each 
evaluation visit. Medications may be categorized for reporting purposes. 
4.5.9 Adverse Events 
Adverse events will be documented according to Section 7.2. 
4.6 Success/Failure Criteria 
Determinations of the successfulness of the treatment will be made on 2 levels, the 
individual participant level and in terms of the overall treatment group success 
relative to the sham control group. Each level has its own criteria for success. 
4.6.1 Participant Success 
The primary outcome success measure for individual participant success 
(responder) is defined as at least 30% improvement (decrease) in the rTNSS 
from baseline at the 3-month primary endpoint. 
4.6.2 Participant Failure 
A participant will be considered a nonresponder at the 3-month evaluation if 
the success criterion has not been attained. 
4.6.3 Study Success 
The study will be considered a success if the proportion of participants 
achieving a successful outcome (responder) that received treatment with the 
RhinAer procedure is statistically significantly greater than the proportion 
achieving individual success when treated with the sham control procedure 
when evaluated at 3 months after the procedure.  

 
 
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4.7 Duration of the Study 
The primary outcome will be evaluated at 3 months. In addition, evaluations at 6, 12, 
and 24 months after treatment will extend follow-up to 2 years for evaluation of 
longer-term efficacy. Participants receiving the sham procedure and meeting original 
eligibility requirements may elect to crossover and receive the active RhinAer 
procedure within 30 days after the 3- or 6-month evaluation with continued follow-
up for 24 more months for a total of up to 31 months of follow-up. Enrollment is 
anticipated to be completed within 12 months. Therefore, total study duration is 
anticipated to be approximately 43 months. 
4.8 Site Staffing and Responsibilities of Study Personnel 
The principal investigator is responsible for ensuring that he/she has sufficient and 
qualified staff to conduct the clinical study and that all study-related tasks have been 
appropriately delegated and documented. Roles may include: 
• Treating physician – The treating physician will perform the procedure and 
discharge assessments.  The treating physician must be a medical doctor with 
experience in ENT procedures and trained in administering the RhinAer 
procedure. 
• Blinded physician evaluator (not required) – A physician experienced in ENT 
procedures, trained for participation in this study, and unaware of the 
treatment received may be used to conduct the follow-up nasal assessment.  
The blinded evaluator may also be responsible for the initial assessment and 
treatment of adverse events; however, in some cases it may be necessary to 
refer the event to the treating physician. If a blinded evaluator is not available, 
the treating physician or principal investigator will conduct the follow-up 
assessments. 
• Oversight of participant reported outcomes and other data collection – 
Medical or office staff with relevant knowledge and experience as determined 
by the principal investigator to interact with study participants to ensure 
collection of study data and participant reported outcomes. Ideally, these 
individuals would be unaware of the treatment received by the participants. 
Due to differences between the actual and sham control procedures, staff may also 
become aware of the treatment being administered. Staff with knowledge of the 
treatment assignment should not communicate any information to the participant or 
blinded evaluator (if used) in order to minimize any potential bias. 
4.9 Device Description 
The RhinAer procedure incorporates use of the RhinAer Stylus (Model FG815), 
which is a cleared (FDA - K192471) disposable handheld device capable of 
delivering bipolar radiofrequency energy to tissue, and the Aerin Console (Model 
FG226), a cleared (FDA - K162810) RF generator with temperature control capable 
of delivering very low doses of energy. 

 
 
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The RhinAer Stylus (Figure 1) consists of a handle, shaft and treatment tip. An array 
of bipolar electrodes is positioned on a nonconductive tip (Figure 2) that is attached 
to the handle via a nonconductive shaft. A temperature sensor is located on the Stylus 
tip to monitor tissue temperature during RF energy delivery. The Stylus is powered 
by an external temperature-controlled radiofrequency generator via a flexible cable 
(Figure 3). The Stylus incorporates features to allow compatibility with and 
authentication by only the Aerin Console. The connector for the RhinAer Stylus has 
a pin configuration that prevents its use with other RF generators, making it only 
compatible with the Aerin Console. Authentication of the Stylus is achieved via a 
crypto chip that is built into the Stylus handle assembly. The chip is read and written 
to by the Aerin Console. Information stored on the chip includes the Stylus model 
information, default treatment parameters (Power 4W, Temperature 60 °C, Duration 
12s, Cooling Time 0s), custom treatment setting ranges (Power 3-5W, Temperature 
50-70°C, Duration 10-18s, Cooling 9-12s), usage timestamp data, and a count of the 
remaining treatment cycles (based upon pre-set maximum). 
The RhinAer Stylus is temporarily inserted into the nose to access the treated area. 
The Stylus requires the application of conductive media to the treatment tip prior to 
use. The conductive media helps to ensure good contact with tissue at all points of 
the treatment tip to facilitate energy transmission. Application of the RF energy is 
controlled by a foot switch connected to the Console. The RhinAer Stylus treats 
symptoms of chronic rhinitis by modifying the tissues of the nasal airway through 
the use of low doses of radiofrequency energy to destroy tissue in the posterior nasal 
nerve regions. The low-power radiofrequency energy generates heat within the 
submucosal tissue, destroying local tissue, mucous cells, and glands, and creating a 
coagulation lesion. This destruction of tissue in posterior nasal nerve regions 
improves symptoms of chronic rhinitis. 
The procedure requires local anesthesia only. The Stylus is manufactured and 
supplied sterile and for single use only by Aerin Medical and may be used to treat 
both nostrils of the patient. 
 
 

 
 
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Figure 1.  RhinAer Stylus 
 
 
 
 
Figure 2.  RhinAer Stylus tip 
 
 

 
 
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Figure 3.  Aerin Console with RhinAer Stylus 
4.10 Risk/Benefit Analysis 
4.10.1 Risks 
Potential risks associated with the use of the RhinAer Stylus do not differ from 
commonly used devices and treatments for chronic rhinitis, but due to the 
nonsurgical nature of the therapy, small treatment area, low energy delivery, 
and lack of need for general anesthesia, the overall risk to the participant may 
be less than presented by other surgical treatments. 
Potential risks associated with the use of the RhinAer Stylus and the associated 
local anesthetics are listed below. Participants will be monitored closely as part 
of this study to allow for early detection of potential problems and prompt 
treatment if required. 
Adverse events or side effects that may occur as a result of the treatment 
include: 
• External deformity 
• Blanching (generalized whiteness) 
• Bruising including around the orbital area (black eyes) 
• Infection 
• Bleeding (other than during the treatment at treatment sites and greater 
than anticipated by the investigator) 

 
 
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• Mucosal changes 
• Scar formation leading to nasal obstruction 
• Sensory changes at treatment site 
• Dry eye 
• Vasovagal response secondary to the procedure 
Anticipated observations that are expected in and around the treatment area and 
are considered minor include: 
• Inflammation / generalized redness 
• Temporary swelling, edema 
• Temporary numbness/tingling 
• Temporary soreness/pain 
• Mild bleeding at anesthetic injection and/or treatment site (not requiring 
physician-level intervention, such as cautery) 
• Temporary nasal obstruction from tissue edema 
• Disruption of mucosal flow/intranasal crusting 
• Scab formation. 
These observations will be assessed in the nasal assessment and recorded at 
study visits if they occur. Should any of the following require mitigation by the 
treating physician or be greater in severity or degree of incidence than 
anticipated, they will be considered an adverse event and will be recorded on 
the study Adverse Event CRF. 
Symptomatic improvements may not be achieved in all participants receiving 
the RhinAer procedure and may not be durable beyond the 3-month evaluation 
in all participants with relief at 3 months. 
An additional risk to participants receiving the sham procedure is a potential for 
higher likelihood of the treatment not relieving their chronic rhinitis symptoms 
compared to those receiving the RhinAer procedure. 
4.10.2 Mitigation of Risks 
The study was developed based on previous preclinical and clinical experience 
and includes a number of steps to minimize any additional risks to participants 
in the study: 
• Careful consideration has been given to the inclusion/exclusion criteria 
in order to select appropriate candidates for treatment. 
• Patients will be fully informed of the study requirements prior to 
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• Only physicians with experience in nasal surgical and minimally 
invasive procedures, and with specific training using the RhinAer Stylus 
for performing the RhinAer procedure will be permitted to participate 
in the study. 
• The study will be reviewed and approved by an Institutional Review 
Board(s) and conducted according to applicable regulations with 
ongoing review by the IRB. 
• Study procedures, follow-up, and study monitoring are designed to 
detect and respond to any adverse events in a timely manner. 
• Preclinical mechanical and bench evaluations have been conducted to 
demonstrate that the design characteristics of the study device are 
appropriate for reliable clinical use of the device. 
• The RhinAer Stylus and Console have been cleared for use by the FDA 
based in part on prior clinical studies demonstrating safety and efficacy 
of their use. 
• Participants receiving the sham control procedure will be offered the 
RhinAer procedure if they have not responded to the sham procedure by 
the 3- or 6-month evaluation. 
4.10.3 Benefits 
The potential benefit associated with the RhinAer procedure is to offer a 
minimally invasive treatment method that has been shown in a previous study 
to help alleviate symptoms of chronic rhinitis and which has been cleared for 
use by the FDA. The RhinAer procedure treats symptoms of chronic rhinitis by 
modifying the tissues of the nasal airway through the use of low doses of 
radiofrequency energy to destroy tissue in the posterior nasal nerve regions. The 
low-power radiofrequency energy generates heat within the submucosal tissue, 
destroying local tissue, mucous cells, and glands, and creating a coagulation 
lesion. This destruction of tissue in posterior nasal nerve regions improves 
symptoms of chronic rhinitis. These benefits may last beyond the length of the 
study. 
The procedure will be provided at no cost to participants. Participants 
randomized to the sham control procedure will be offered the opportunity to 
receive the RhinAer procedure within 30 days after the 3- or 6-month evaluation 
if the control procedure has not alleviated their symptoms.  
4.10.4 Potential Risks to Participant Confidentiality  
In all clinical studies, confidentiality of protected health information may be 
breached due to study-related activities beyond those of routine clinical care. 
This risk will be minimized by not entering personally identifying information 
into the EDC system through the study’s electronic case report forms (eCRF). 
Risks to participant confidentiality are further minimized by allowing only 

 
 
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authorized individuals to access the EDC system and the database that stores 
the electronically entered data. The 21CRF Part 11 compliant and validated 
system maintains audit trails on all entries, changes or corrections to eCRFs. If 
a person with authority to complete but not sign eCRFs makes changes to an 
already signed eCRF, the investigator will be required to re-sign the eCRF, 
thereby protecting the integrity of the data collection process and the data. 
4.10.5 Study Justification in Relation to Risk 
The study sponsor believes that any additional risks presented by participating 
in this study are very low and that adequate testing, safeguards, and risk 
monitoring have been incorporated into the study to further minimize and 
mitigate the risks relative to the potential benefits, including relief from 
symptoms of chronic rhinitis, that may be realized by participation in this study. 
5.0 
Study Schedule and Procedures 
This section provides summaries of the study schedule of events and flow of 
participants through the study, as well as more detailed information on study 
procedures and processes. 
5.1 Schedule of Events 
 
Screening 
Treatment 
Follow-up  
(office) 
Extended follow-
up (remote) 
  Procedure 
    Immediate 
Postprocedure 
  1 Month 
(4 weeks) 
  3 Months1  
  (13 weeks) 
  6 Months1 
  (26 weeks) 
 12 Months 
 (52 weeks) 
 24 Months 
 (104 weeks) 
Window (days) 
(-30) 
(0) 
(0) 
(± 7) 
(± 14) 
(± 30) 
(± 30) 
(± 30) 
Activity / Assessment 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
Nasal assessment (physical, endoscopic) 
X 
X2 
X 
X 
X 
X 
 
 
Current medication use (study relevant) 
X 
X2 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
 
 
 
 
 
 
 
VAS nasal pain  
 
 
X 
X 
X 
 
 
 
Rhinitis symptoms (rTNSS, cough, and 
postnasal drip)  
X 
X2 
 
 
X 
X 
X 
X 
MiniRQLQ 
X 
X2 
 
 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
 
X 
X 
X 
X 
Adverse Events 
X 
X2 
X 
X 
X 
X 
X 
X 
1Control participants eligible to crossover and receive RhinAer procedure. 
2Repeat only on day of treatment if screening was conducted after 72 hours day of procedure. 
 
 
 
 
 
 
 

 
 
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5.2 Participant Flowchart 
 
No 
Yes 
Yes 
Consented Participants 
RhinAer procedure 
Sham procedure 
Randomization 2:1 
4-week follow-up 
13-week follow-up 
4-week follow-up 
13-week follow-up 
Meets 
eligibility 
criteria 
Primary Endpoint 
Extended remote 
follow-up 
 
12 months 
 
24 months 
Elects to  
Exit Study 
Follow-up 
4 weeks 
 
13 weeks 
 
26 weeks 
 
Extended remote 
follow-up 
 
12 months 
 
24 months
26-week follow-up 
No 
 Continue to 
26-week 
Follow-up  
Elects  
RhinAer 
procedure 
Yes 
Meets 
eligibility 
criteria  
No 
No 
Exit from study 

 
 
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5.3 Enrollment and Baseline Assessment 
Screening 
The investigator or designated research staff will perform an evaluation of the study 
candidate for study eligibility, which may include a history and physical examination 
of the nasal area, review of overall medical history, understanding of general health 
and discussion of any conservative measures used chronic rhinitis. In addition, 
patients will complete standard questionnaires to document current symptoms 
associated with chronic rhinitis (rTNSS, MiniRQLQ). 
Patients must be diagnosed with chronic rhinitis prior to entry into the study. The use 
of diagnostic procedures and screening tests to determine a diagnosis and assess 
whether patients are appropriate candidates for inclusion in the study is an appropriate 
pre-entry activity. While the availability of the study may be discussed with a 
prospective participant without first obtaining consent, informed consent must be 
obtained prior to initiation of any clinical procedures dictated by the protocol that are 
performed solely for the purpose of determining eligibility to participate in the study. 
Once the pretreatment assessments are completed the study procedure should be 
scheduled within 30 days. 
Informed consent 
Informed consent must be obtained in accordance with FDA regulation 21 CFR Part 
50. The clinical investigator or designated staff member is responsible for ensuring 
that informed consent is obtained for each participant prior to participation in the 
study. The patient must be fully counseled with an explanation of the study 
background, randomized nature of the study, study procedure, follow-up schedule, 
and informed of their options, risks and benefits, and have every opportunity to ask 
questions about participation in the study. This process includes a thorough 
explanation of the informed consent document that the patient will be asked to sign 
acknowledging that they understand and desire to participate in the study. The 
explanation and discussion should be conducted in such a way as to: 
• avoid coercion or influence of patient to participate in the study, 
• ensure the patient understands that their legal rights are not waived at any 
time, 
• use language at a level the patient can understand, and  
• ensure the patient understands that after providing signature on the Informed 
Consent, the patient may still withdraw at any time before, during or after 
study treatment. 
Evaluation of inclusion and exclusion criteria 
The Screening Visit / Study Eligibility CRF will be used to document the 
participant’s eligibility status. 

 
 
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Pretreatment (baseline) data and assessments 
The following data will be obtained prior to treatment and recorded on the Baseline 
Visit Demographics and Treatment History CRF: 
• Demographics 
o Sex 
o Height (inches) 
o Weight (pounds) 
o Date of birth 
o Race / Ethnicity 
• Nasal symptoms, history of treatments, nasal visual exam 
o History (duration) of rhinitis 
o Rhinitis triggers (allergic or nonallergic) 
o Medications used to treat rhinitis 
o Previous ENT treatments 
o Turbinate enlargement, nasal polyps, and other significant findings 
The nasal assessment data (each nostril) including photos or video (physical and 
endoscopic) will be recorded and entered into EDC. If treatment is not provided the 
same day as screening, then this assessment will be repeated on the day of the 
procedure immediately prior to treatment. 
Current use of medication, devices, or other therapies for symptoms of chronic 
rhinitis, including medication name, frequency, and dose will be detailed on the 
Medication Log. 
Rhinitis symptom severity, including the rTNSS, cough and postnasal drip, will be 
completed by the participant on the rTNSS CRF. If treatment is not provided the same 
day as screening, then this assessment will be repeated on the day of the procedure 
immediately prior to treatment. 
The MiniRQLQ will be completed by the participant on the MiniRQLQ CRF. 
5.4 Treatment Visit and Procedure 
Randomization should occur just prior to performing the procedure but allowing 
enough time for preparation of the selected treatment. If the participant meets 
eligibility criteria and signs the IRB approved informed consent, the participant is 
considered enrolled once the RhinAer Stylus enters the nasal passageway.  
The treatment procedure is summarized below. Consult the RhinAer Stylus and Aerin 
Console IFUs for full detail of the treatment procedure and step-by-step instructions 
for preparation and use of the RhinAer Stylus and Aerin Console. 

 
 
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Preparation  
The procedure will be performed in the study clinic. The participant will be in a 
reclined or supine position on the procedure table in the physician’s office. A visual 
physical and endoscopic nasal assessment conducted just prior to the procedure will 
be documented on the appropriate CRF. The study physician will map out the 
treatment area by evaluating the middle meatus and surrounding structures of the 
nasal cavity to understand access of the study device to the mucosal area for 
treatment. Participants will have both posterior nasal nerve areas treated in a single 
study procedure session. Each nostril will be treated at up to 5 nonoverlapping 
positions within the posterior portion of the middle meatus and posterior portion of 
the inferior turbinate (Figure 4). 
 
Figure 4.  RhinAer Stylus in the nose. 
The physician will anesthetize the treatment area by using a topical swab/gauze or 
spray of lidocaine to numb the mucosal tissue, wait approximately 20 minutes, and 
then inject anesthesia to the treatment area after initial numbness has occurred. The 
sham control participants will receive the same anesthesia as the actively treated 
participants. 
Treatment administration 
An endoscope will be inserted into the nasal cavity so the physician can visualize the 
mucosal area of treatment. The RhinAer Stylus will then be inserted to access the 
treatment area.  The Stylus will be connected to the Aerin Console generator and the 
RF energy level will be set on the generator. 
The default settings for the RhinAer Stylus will be used for the study:  
Temperature  
60 °C 
Power  
 
4 Watts 
Treatment Time 
12 secs 
Cooling Time  
0 secs 

 
 
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The physician will apply the treatment tip of the RhinAer Stylus to the target tissue 
prior to energy delivery. The energy is turned on by maintaining downward pressure 
on the foot pedal. With the energy on, the physician continues to apply the Stylus tip 
to the mucosal surface consistent with the IFU. A tone will be heard when energy is 
being delivered until the treatment is complete. After the treatment time is reached, 
the Aerin Console will cease to delivery energy and reset for subsequent treatments.  
When conducting a sham control procedure, the physician will activate an audible 
tone mimicking the activation of the Aerin Console; however, no energy will be 
transmitted to the Stylus. The physician should apply the Stylus to the mucosal 
surface with similar pressure and in similar locations as would be done if energy was 
actually being applied. 
No repeat ("touch-up") procedures will be permitted during the study follow-up 
period.  
Procedure data collection 
Data relating to the procedure and the products used will be recorded on the 
Procedure CRF. The following information will be recorded: 
• Date of procedure 
• Preprocedure nasal assessment (each nostril) including photos or video 
(physical and endoscopic) 
• Preprocedure and procedure medications 
• RhinAer Stylus and Aerin Console information  
• Aerin Console settings 
• Procedure start and end times 
• Number of sites treated 
• Occurrence of device malfunction, protocol deviation, or adverse events. 
5.5 Postprocedure Assessments and Care 
An endoscopic nasal assessment will be conducted prior to discharging the 
participant and reported on the Procedure CRF. 
Participants will be asked to indicate the pain level experienced during the study 
procedure from anesthesia delivery to procedure completion using the VAS pain 
score instrument (vertical line marked on the 100 mm line) on the Pain VAS CRF. 
At the discretion of the physician, the following care may be provided: 
• Apply compression to the treatment area internally for 5 minutes. 
• Apply petroleum jelly to the treatment area as needed.  
• Use of nasal saline spray or ointment as needed. 
• The participant should be instructed not to blow their nose for 24 hours. 

 
 
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Participants should have their first follow-up visit (4 weeks) scheduled within the 
visit window prior to release. 
Participants should not generally receive other concomitant nasal treatment therapies 
or interventions after the procedure or during the study follow-up period to avoid 
confounding the evaluation of the effect of the treatment, unless the additional care 
is in response to an adverse event or is considered in the best interest of the 
participant. Therapies, interventions, and pain medication will be monitored at 
follow-up evaluations.   
5.6 Follow-up Evaluations and Study Exit 
Follow-up visit dates will be calculated from the study procedure date. Follow-up 
visits should be scheduled within the specified visit windows described in Section 
5.1 and Table 1 (Section 8.3.2). In-office follow-up evaluations are scheduled for 4 
weeks (1 month), 13 weeks (3 months), and 26 weeks (6 months) after the treatment 
procedure. Evaluations at 12 and 24 months will be conducted remotely by telephone 
assessment by site personnel. The timing of all follow-up evaluations is based on the 
date of the procedure and should not be altered based on the actual time of preceding 
follow-up visits. Participants who make nonstudy visits should be evaluated for 
possible adverse events and an Adverse Event CRF should be submitted if 
appropriate. 
All participants who receive the RhinAer procedure, as well as sham procedure 
participants who choose to have the RhinAer procedure within 30 days after their 3, 
or 6-month evaluation, should be followed through the final evaluation visit at 2 years 
postprocedure regardless of their success/failure classification.  Participants who 
receive the sham procedure and are evaluated at 13 weeks or 26-weeks and continue 
to meet all of the original inclusion and exclusion criteria, including rTNSS ≥ 6, will 
be offered the opportunity to have the RhinAer procedure performed. Participants 
who choose to have the procedure will maintain their original study ID and will 
follow the same pretreatment, treatment, and follow-up processes as any newly 
enrolled participant. 
Sham control procedure participants who choose not to have the RhinAer procedure 
or who fail to meet inclusion and exclusion criteria may elect to exit from the study 
following the 3- or 6-month evaluation. Refer to the Participant Flowchart, Section 
5.2 for depiction of study process.   
Every effort should be made to avoid having participants withdraw from the 
study(Section 9.5). If a participant does choose to withdraw from the study, it is very 
important to record information regarding the reason(s) and the last known status of 
the participant. 
The following assessments will be conducted as indicated for each follow-up time 
point and recorded on the corresponding CRFs: 

 
 
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In-office evaluations: 4-week (1-month), 13-week (3-month), and 26-week (6-
month) follow-up 
• Nasal assessment (each nostril) including photos or video 
• Current use of medication, devices or other therapies for symptoms of chronic 
rhinitis, including medication name, frequency, and dose 
• Participant reported change in use of as needed medications and devices for 
chronic rhinitis symptoms (completed by participant) (no 1-month) 
• rTNSS (completed by participant) (no 1-month) 
• Cough and postnasal drip symptoms (completed by participant) (no 1-month) 
• MiniRQLQ (completed by participant) (no 1-month) 
• VAS pain score (completed by participant)  
• Adverse events 
Remote (telephone) evaluations: 12-month (52-week) and 24-month (104-week) 
follow-up  
• rTNSS (verbal administration by site personnel) 
• Cough and postnasal drip symptoms (verbal administration by site personnel)  
• MiniRQLQ (verbal administration by site personnel) 
• Participant reported change in use of as needed medications and devices for 
chronic rhinitis symptoms (verbal administration by site personnel) 
• Patient satisfaction survey (verbal administration by site personnel)  
• Current use of medication or other therapies for symptoms of chronic rhinitis, 
including medication name, frequency, and dose (study staff follow-up 
required if participant indicates changes) 
• Adverse events (study staff follow-up required if participant indicates 
changes). 
Participants meeting the study requirements as planned will be exited upon 
completion of their 24-month (104-week) follow-up visit. If a participant reaches the 
24-month (104 week) follow-up visit and is experiencing a new or ongoing adverse 
event, the study sponsor should be contacted to discuss the need and/or methods for 
continued surveillance of the event.  
5.7 Product Handling and Accountability 
A system that allows tracking of orders, shipping and returns will be used to control 
RhinAer Stylus and Aerin Console inventory. The devices will be packaged and 
labeled to clearly indicate that they are for clinical study use only and must only be 
used for participants enrolled in this study. All devices not used must be returned to 
the sponsor or disposed of in accordance with the sponsor’s instructions. The 

 
 
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investigator is responsible for adequate record keeping regarding the receipt, use, and 
final disposition of study inventory. 
6.0 
Statistical Considerations 
6.1 Study Design 
This is a prospective, multicenter, randomized, sham-controlled study to compare the 
RhinAer procedure for treatment of chronic rhinitis with a sham procedure that 
duplicates the actual procedure as closely as possible absent the delivery of 
radiofrequency (RF) energy to the nasal tissue. Participants will be randomized using 
a 2:1 allocation to receive either the RhinAer procedure or a sham procedure 
(control). This study is designed to demonstrate the superiority of the active RhinAer 
treatment compared to the sham control. 
6.2 Study Hypotheses 
The null hypothesis (H0) for this superiority study is that there is no difference 
between the success (responder) rate for the sham control and the success (responder) 
rate for the RhinAer procedure: 
H0: πC - πT = 0 vs. H1: πC - πT ≠ 0 
where: 
πC=proportion of responders in the sham procedure control group 
πT=proportion of responders in the RhinAer procedure treatment group. 
Rejection of the two-sided null hypothesis in favor of the alternative (H1) hypothesis 
means that there is evidence for a statistically significant difference in responder rates 
between the 2 groups. 
6.3 Sample Size Estimate 
The study will enroll up to 120 participants. The power analysis was performed such 
that there is adequate power to reject the null hypothesis of no difference between 
treatments. Sample size estimation was based on the test for differences between 2 
proportions33 using an exact test and on the following assumptions: 
• Significance level α = 0.05 (two-sided) 
• Power = 80% 
• πC = 0.50 (allowance for a 50% control responders) 
• πT = 0.80 (assumed 80% responders in the treated group) 
• Treatment allocation is 2:1 
• 10% dropout and nonevaluable. 
The 80% responder rate assumed for the active RhinAer procedure group is an 
estimate based on the prior clinical study of this procedure in which 43 of 50 

 
 
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participants (86%) were responders at 12 weeks. The one-sided lower 95% 
confidence bound on the responder rate of 86% is 76%, which supports the estimate 
of 80% responders assumed for the purpose of sample size calculation. 
Studies of randomized placebo-controlled efficacy trials of drugs used to treat allergic 
rhinitis have found high response to placebo including up to a 57% share of the 
therapeutic effect for AR34 and up to a 25% reduction in TNSS for perennial allergic 
rhinitis35 with a strong placebo effect observed where the evaluating parameters tend 
to be physical or subjective rather than objective indicators of drug efficacy.36 The 
50% responder rate assumed for the sham control procedure is based on the literature 
for placebo and sham controls in therapeutic and device studies suggesting from 30% 
to 60% responder rates, with device studies tending to be at the higher end of the 
range37. 
The minimum number of participants to achieve 80% power with a 2:1 active 
treatment to sham control allocation is 66 in the active treatment group and 33 in the 
sham group. The sample size, allowing for 10% loss (nonevaluable) in each group 
and adjusting for a balanced distribution across 20 sites is 120 participants (80 active 
treatment (RhinAer procedure), 40 sham procedure control). 
It is anticipated that participants will be enrolled at sites on a competitive basis; 
however, a reasonable balance of participants among sites may be maintained by 
potentially capping enrollment at individual sites based on the final number of 
participating sites. 
6.4 Timing of Analysis 
The primary evaluation phase of the study lasts until all participants have reached the 
primary endpoint at 13 weeks (3 months) postprocedure. The primary and secondary 
endpoints will be analyzed using the data from the primary evaluation phase for an 
interim study report when these data become available. Informational outcomes will 
be analyzed and included in interim reports after all participants have reached each 
of the successive follow-up time points. A final study report will be provided after all 
participants have reached the final follow-up evaluation of the extended follow-up 
phase of the study, including sham procedure control participants who subsequently 
received the RhinAer procedure. 
6.5 Analysis Populations 
The primary endpoint analysis will be based on the intent-to-treat (ITT) principle. 
Participants will be analyzed in the originally randomized treatment group regardless 
of actual treatment received. The effects of protocol deviations will only be examined 
when the validity of the study conclusion is in question. All secondary and other 
analyses and reports will include an ITT population analysis. Following data 
reporting conventions, statistics on the per protocol population will also be reported. 
The per protocol population is defined as all participants who received treatments, 
with 13-week (3-month) follow-up data and no major protocol deviations. 

 
 
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6.6 Missing Data 
All missing data in each treatment group will be imputed for the primary endpoint by 
assuming the missing outcomes are nonresponders. In addition, a post hoc sensitivity 
analyses may be performed, including a worst-case analysis (all missing primary 
outcomes in the RhinAer procedure group are considered nonresponders and all 
missing outcomes in the sham procedure control group are responders) and/or a 
change-point analysis, to assess the effect of missing data on the primary analysis. 
The results of the sensitivity analysis will not be used to adjust the conclusions drawn 
from the primary analysis. 
Secondary outcome measures and additional observational measurements will be 
analyzed by using available data only. 
6.7 Pooling 
All study data will be pooled across study sites to facilitate hypothesis testing in 
accordance with the sample size estimation and power analysis (Section 6.3). 
Comparability between study sites may be shown using summary statistics calculated 
by site. 
6.8 Participant Disposition 
A detailed description of participant disposition will be provided by treatment group 
using a CONSORT diagram and summaries of participants falling in various 
subgroups of interest, such as, enrolled but not treated with any study treatment, not 
treated as randomized, discontinued, excluded from ITT, protocol deviations, deaths, 
and withdrawals. All study population exclusions and reasons will be summarized. 
All randomized participants entered in the study will be accounted for in the 
summary. Follow-up by visit will be presented, showing theoretical, expected, and 
actual follow-up visits. 
6.9 Demographics and Characteristics 
Demography, baseline characteristics and the comparability of active treatment group 
and sham control group participants will be summarized using frequencies and 
percentages for categorical factors and mean, median, standard deviation, minimum 
and maximum for continuous factors. Demographic characteristics will be reported 
to describe the profile of samples. Comparability between treatment groups will not 
be statistically assessed in this prospective randomized clinical trial.  
Baseline covariates with possible impact on outcomes at 3 months are: 
• Age  
• Race 
• Sex 
• BMI 
• Allergic status (allergic rhinitis - nonallergic rhinitis). 

 
 
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Results may be evaluated by allergic status if sufficient numbers are obtained in both 
categories. 
6.10 Primary Endpoint Analysis 
Primary efficacy will be evaluated using the proportions of successful outcomes 
(responders) on the primary outcome measure (improvement in rTNSS) at 13 weeks. 
The proportions of responders at 13 weeks in each group will be compared using 
Fisher’s Exact test. 
Confidence intervals (95%) will be provided for all proportions and comparisons. 
6.11 Secondary Endpoints Analysis 
Secondary endpoints will be tested only after the primary objective of the study is 
met. Confidence intervals (95%) will be included for all secondary outcome 
measures. 
• Mean change in the rTNSS from baseline to 13 weeks 
The mean changes from baseline at 13 weeks in each group will be 
compared with a 2-sided t-test with a null hypothesis of no difference 
between groups. 
• Device-related and procedure-related serious adverse events through 13 
weeks 
The proportions of serious device-related adverse events through 13 weeks 
in each group will be compared using Fisher’s Exact test. 
6.12 Other Outcome Measures Analyses 
Additional outcome measures will be collected for information and hypothesis 
generating purposes. The primary analysis methods will be descriptive and 
exploratory and presented by evaluation to more completely understand the time 
course of treatment effect. Measures will be summarized using frequencies and 
percentages for categorical measures and mean, median, standard deviation, 
minimum and maximum for continuous factors. Confidence intervals for differences 
between treatment groups will be included where appropriate. Statistical comparisons 
will either not be performed or used for information purposes. Proportions may be 
compared using exact tests or chi-square tests. Continuous outcomes may be 
compared using t-tests, ANOVA or nonparametric equivalents. Repeated measures 
ANOVA may be used for longitudinal analysis across evaluations. 
Other outcome measures include: 
• Nasal Assessment - The visual physical and endoscopic assessment factors 
will be summarized to include frequency and percentage of responses in 
each category for each component of the nasal assessment by treatment 
group at baseline, just prior to treatment, immediately after treatment, at 4 
weeks, and at 3 months after the procedure.   

 
 
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• Visual analog scale (VAS) for pain - Summary will include mean VAS pain 
scores assessed posttreatment, 4 weeks, and at 3 months for both treatment 
groups. 
• rTNSS - The rTNSS and its individual components will be subject to 
multiple summary methods and analyses including the:  
o Mean and mean change from baseline at the 3-, 6-, 12-, and 24-
month follow-up evaluations for each group and differences 
between groups. 
o Mean, mean change from baseline, and response distribution of the 
4 components of the rTNSS (rhinorrhea, nasal congestion, nasal 
itching, and sneezing) at baseline and the 3-, 6-, 12-, and 24-month 
follow-up evaluations for each group and differences between 
groups. 
o Proportion of responders based on 30% improvement in rTNSS at 
the 3-, 6-, 12-, and 24-month follow-up evaluations for each group 
and differences between groups. 
• Other rhinitis symptoms (cough and postnasal drip) - Mean, mean change 
from baseline, and distribution of the 4 response categories (0-3 points)  at 
baseline and the 3-, 6-, 12-, and 24-month follow-up evaluations for each 
group and differences between groups. 
• MiniRQLQ: The MiniRQLQ and its individual components will be subject 
to multiple summary methods and analyses including the: 
o MiniRQLQ mean and mean change from baseline at the 3-, 6-, 12-, 
and 24-month follow-up evaluations for each group and differences 
between groups. 
o MiniRQLQ domain scores (nose symptoms, eye symptoms, non-
eye/nose symptoms, sleep problems, practical problems, activity 
limitations, and emotional function) at baseline and the 3-, 6-, 12-, 
and 24-month follow-up evaluations for each group and differences 
between groups.. 
• Participant satisfaction assessment - mean response for each of the 5 survey 
questions will be summarized by group at the 3-, 6-, 12-, and 24-month 
follow-up evaluations. 
• Change in amount of PRN medication use for chronic rhinitis symptoms - 
Proportions of participants reporting increase, decrease, or no change in 
medications being used for treatment of  symptoms compared to use prior 
to the procedure will be summarized by group for the 3-, 6-, 12-, and 24-
month follow-up evaluations. 
• Medications - A listing of medications associated with relief or treatment of 
chronic rhinitis symptoms or associated with treatment of adverse events 

 
 
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will be provided by group. Medication use by categories may also be 
presented as percentages of participants in each group.  
6.13 Safety Analysis 
All adverse events will be analyzed for all participants. Adverse events will be coded 
using a custom Aerin Medical dictionary so that adverse events may be categorized 
for analysis at an appropriate level of detail. Listings will be provided to detail 
individual events. The number of participants, number of AEs, and the proportion of 
participants reporting each AE will be summarized. Seriousness and severity of AEs 
and their relationship to the device and procedure will be summarized. A time course 
of adverse events will be presented. Any unexpected adverse device experiences or 
adverse events that occur at an unexpectedly high incidence rate will receive detailed 
analyses. Narratives will be presented for all deaths, serious adverse events, 
unexpected adverse device experiences, and participants withdrawn due to an adverse 
event. 
6.14 Extension Phase Analysis 
The extension phase analyses will be similar to those detailed above with a particular 
emphasis on the summarization of all adverse events occurring throughout the entire 
study and the maintenance of the treatment effect over time. Missing data analyses 
and imputation will not be performed on data collected during the extension phase. 
6.15 Standard Methods of Report 
Summary descriptive statistics including means, medians, standard deviations and 
histograms for continuous measures, and frequencies and percentages for categorical 
outcomes will be presented for all variables of interest. Outcome measures (primary, 
secondary, and informational) will be presented by treatment group and time. 
7.0 
Adverse Events and Product Complaints 
7.1 Adverse Events 
Adverse events (AEs) may occur during the treatment phase or during the follow-up 
phase. Adverse events occurring after the baseline assessment but before the 
treatment procedure will be documented in the participant’s medical record but will 
not count as related to the study device or procedure.   
7.1.1 Definitions 
Following are definitions associated with adverse events: 
Adverse Event (AE) - any untoward medical occurrence, unintended disease or 
injury, or untoward clinical sign or symptom (including an abnormal laboratory 
finding), in subjects whether or not related to the investigational drug or medical 
device product. This includes events related to investigational drug or medical 
device product, comparator and/or events related to the procedures involved. 
For users or other persons, this definition is restricted to events related to 
investigational medical devices. 

 
 
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Serious Adverse Event (SAE) - any untoward medical occurrence that: (a) led 
to death, (b) resulted in a life-threatening illness or injury, (c) resulted in 
permanent impairment of a body structure or body function, (d) required 
inpatient hospitalization or prolongation of existing hospitalization, (e) resulted 
in medical or surgical intervention to prevent permanent impairment to a body 
structure or body function or (f) led to fetal distress, fetal death or a congenital 
abnormality or birth defect. 
Adverse Device Effect (ADE) - Adverse event related to the use of an 
investigational medical device. This includes AEs resulting from insufficient or 
inadequate instructions for use, deployment, implantation, or operation, or any 
malfunction of the investigational medical device and also includes any event 
resulting from use error or from intentional misuse of the investigational 
medical device. 
Serious Adverse Device Effect (SADE) - 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. 
Anticipated Adverse Device Effect (AADE) - A device-related event described 
in the investigational protocol or informed consent for the clinical trial of an 
investigational device. 
Unanticipated (Serious) Adverse Device Effect (UADE or USADE) - A 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. 
Relationship to device and procedure 
The potential relationship of the event to the device or procedure: 
• Not related 
An adverse event for which sufficient information exists to indicate that 
there is no causal connection between the event and the device or 
procedure. The adverse event is due to and readily explained by the 
participant’s underlying disease state or is due to concomitant 
medication or therapy not related to the use of the device or the 
procedure. In addition, the adverse event may not follow a reasonable 
temporal sequence following the treatment procedure. 
• Possibly related 
There is a reasonable possibility that the adverse event may have been 
primarily caused by the device or procedure.  The adverse event has a 

 
 
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reasonable temporal relationship to the use of the device or the 
procedure and follows a known or expected response pattern to the 
device or procedure, but alternative etiology is equally or more likely 
compared to the potential relationship to the use of the device or the 
procedure. 
• Probably related 
There is a reasonable probability that the adverse event may have been 
primarily caused by the device or procedure. The adverse event has a 
reasonable temporal relationship to the use of the device or the 
procedure and follows a known or expected response pattern to the 
device or procedure. 
• Definitely related 
The adverse event has a strong causal relationship to the device or 
procedure. The adverse event follows a strong temporal relationship to 
the use of the device or the procedure, follows a known response pattern 
to the device or procedure, and cannot be reasonably explained by 
known characteristics of the participant’s clinical state or other 
therapies. 
Every effort should be made to determine the cause of each adverse event, 
because a judgment must be made as to the relationship to the device or 
procedure. If an investigator cannot assign a causality category the event will 
be considered possibly related for reporting and analysis. 
NOTE: The occurrence of a diagnostic or elective surgical procedure for a pre-
existing condition, unless the condition becomes more severe or increases in 
frequency, would not be considered procedure-related or device-related. 
Intensity of adverse events:  
• Mild 
The adverse event is noticeable to the participant but does not interfere 
with routine activity. 
• Moderate 
The adverse event interferes with routine activity but responds to 
symptomatic therapy or rest. 
• Severe 
The adverse event significantly limits the participant's ability to perform 
routine activities despite symptomatic therapy. The adverse event 
requires medical or surgical treatment or results in hospitalization. 
7.1.2 Documentation and Reporting of Adverse Events 
All adverse events must be reported on the Adverse Event Form. All adverse 
events will be followed until they are adequately resolved or reach a chronic, 

 
 
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stable state. If a participant reaches the 24-month follow-up visit and is 
experiencing a new or ongoing adverse event, the study sponsor should be 
contacted to discuss the need and/or methods for continued surveillance of the 
event. Adverse events will be evaluated by the investigator and differentiated 
by: 
• Seriousness 
• Intensity (mild, moderate, severe) 
• Causality (in relation to the device or procedure) 
• Unexpectedness. 
Signs and symptoms considered normal postprocedure recovery (eg, 
postprocedure pain, transient sensory symptoms, fever, postanesthesia 
symptoms) do not have to be reported as adverse events. If these events require 
treatment outside that which is considered normal, they should be reported as 
adverse events. 
All adverse events classified as an Unanticipated Adverse Device Effect, 
Serious Adverse Device Effect, or Serious Adverse Event need to be 
reported to the Sponsor within 24 hours of learning of the event.  
Sponsor Contact: Anais Laborde  
Telephone: (650) 518-9624 
email: alaborde@aerinmedical.com 
Investigators must also report promptly all unanticipated problems to their IRB 
involving risks to participants or others and report adverse events according to 
the local reporting requirements. Reporting instructions and contact 
information will be provided in the site’s Regulatory Binder for this study. 
7.2 Product Complaints 
7.2.1 Definitions 
Product Complaint - Any written, electronic or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, 
effectiveness, or performance of an Aerin product (medical device) after it is 
released for distribution [per 21 CFR 820.3(b)]. 
Complaint – written, electronic or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, usability, safety or 
performance of a medical device that has been released from the organization's 
control or related to a service that affects the performance of such medical 
device. [per ISO 13485:2016]  
Reportable Complaint – Any product complaint that represents an event, which 
must be reported to a regulatory agency including: 
• US Food and Drug Administration (per 21 CFR Part 803) 

 
 
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• A Competent Authority within the European Community or a Notified 
Body (MDD) 
• The Canadian HPFB 
• Any regulatory agency, within the country of distribution. 
7.2.2 Documentation and Reporting of Complaints 
All product complaints, deficiencies, and malfunctions associated with devices 
will be documented on the appropriate case report form and/or communicated 
to Aerin within 24 hours of first becoming aware of the event.  
8.0 
Study Administration 
This study will be conducted in accordance with elements of E6 Good Clinical Practice 
Consolidated Guidance, ICH, April 1996, Abbreviated Requirements of 21 CFR 812 
for nonsignificant risk device studies, the Declaration of Helsinki, the Belmont Report 
and any conditions imposed by the reviewing IRB or US FDA or other regulatory 
agency. 
The study sponsor has the overall responsibility for the conduct of the study according 
to all applicable regulatory requirements. The study sponsor will have certain direct 
responsibilities and will delegate other responsibilities to the investigator and study 
site. The study sponsor and investigator will ensure that the study is conducted 
according to all applicable regulations. All personnel participating in the conduct of 
this study will be qualified by education and experience to perform their tasks. 
The study sponsor, treating physician, or any person acting for or on behalf of a sponsor 
or treating physician shall act in accordance the applicable standards, guidelines and 
regulations. 
8.1 Investigator Training 
Site initiation training will occur prior to the first procedure at a site.  Investigators 
will be trained on the treatment procedure and use the RhinAer Stylus and Aerin 
Console. All study staff will be trained, as necessary, to ensure compliance with the 
protocol and regulatory requirements, as well as to ensure accurate data collection. 
Site training will include a detailed review of this protocol, use of the EDC system, 
eCRF completion instructions, adverse event reporting, product handling and 
inventory, randomization instructions, monitoring logistics, and regulatory 
requirements. 
8.2 Study Monitoring 
Study monitoring will be carried out in compliance with FDA regulations and GCP 
guidelines. The first monitoring visit should occur shortly after the first participants 
have been enrolled and at least one treatment has occurred at the site. Subsequent 
monitoring visits will occur as the frequency of enrollment dictates but no less than 
annually. A final close-out monitoring visit will occur when the study has been 
completed or terminated. 

 
 
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The monitoring for this study will be carried out by monitors qualified by experience 
and training who are Aerin Medical employees or individuals contracted by Aerin to 
conduct monitoring activities. 
8.3 Documentation of Study Findings 
8.3.1 Data Management 
A secure EDC and management system will be used for entry, storage, review, 
and management of study data. The system will use the Medrio EDC platform 
(Medrio, Inc. San Francisco, CA) and be compliant with applicable GCP and 
regulatory requirements. Sites will be trained in the use of the system for 
entering study data and uploading supporting documents. Data monitoring will 
be performed to verify data accuracy and ensure queries are resolved. 
8.3.2 Case Report Forms 
All study data will be entered by study personnel through eCRFs into the 
electronic database for each participant enrolled in the study. A unique ID 
number will be assigned to each participant.  
The following CRFs and log will be used in this study and submitted at the 
intervals outlined in Table 1: 
• Screening Visit / Study Eligibility (01) 
• Baseline Visit Demographics and Treatment History (02) 
• Follow-up (03) 
• rTNSS / Cough and Postnasal Drip (04) 
• Procedure (05) 
• Pain VAS - Patient form (06A) 
• Pain VAS - Site (06B) 
• Study Exit (07) 
• Device Malfunction (08) 
• Protocol Deviation (09) 
• Adverse Event Report (10A) (reference AE Code List (10B)) 
• MiniRQLQ (11) 
• Serious Adverse Event / Unanticipated Adverse Device Effect (12) 
• Patient Satisfaction Survey (13) 
• Concomitant Medication Log (14) 
 

 
 
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Table 1. 
Schedule of case report forms and related materials. 
Visit 
Visit window (days) 
CRF 
Other 
Screening / Baseline 
n/a 
01, 02, 04, 11, 14 
Informed Consent 
Nasal assessment images† 
Treatment Procedure 
within 30 days of Baseline‡ 
05, 06A, 06B 
Nasal assessment images† 
4-Week (In-office) 
±3 
03, 04, 06A, 06B, 11 
Nasal assessment images† 
13-Week (In-office) 
±14 
03, 04, 06A, 06B, 11 
Nasal assessment images† 
6-Month (In-office) 
±30 
03, 04, 11, 13 
Nasal assessment images† 
12-Month (Remote) 
±30 
03, 04, 11, 13 
 
24-Month (Remote) 
±30 
03, 04, 07, 11, 13 
 
As Needed 
n/a 
07, 08, 09, 10A, 12, 14 
 
†Transfer to USB flash drive and provide to Sponsor. 
‡If the procedure does not occur on the day of screening the nasal assessment, rTNSS, and MiniRQLQ should 
be repeated, and medication use updated before starting the procedure. 
 
8.3.3 Investigator Responsibilities, Records, and Reports 
Responsibilities 
The investigator is responsible for ensuring that the study is conducted 
according to the protocol and all IRB requirements. In addition, the investigator 
is responsible for obtaining participant’s written authorization for disclosure 
and use of health information as required under the Health Insurance Portability 
and Accountability Act (HIPAA; 45 CFR Parts 160 and 164).   
Records 
The investigator will maintain complete, accurate and current study records.  
Investigator records including: 
1. Relevant communication that documents any agreements or significant 
discussions regarding trial administration, protocol violations, trial 
conduct, or adverse event reporting, including that with the IRB, the 
sponsor, the study monitors, other investigators, and regulatory 
agencies. 
2. Accountability records of receipt, use and disposition of all study 
products, including the type and quantity of the product, the dates of 
their receipt and the lot numbers. 
3. Participant records, including the participant’s informed consent form, 
case history, procedure dictation, adverse events, progress notes, 
follow-up evaluations, case report forms and all supporting documents, 
such as diagnostic studies. 
4. Study Protocol, amendments, and documentation (dates and reasons) of 
any deviations from the protocol. 

 
 
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5. IRB records, including original and ongoing study approvals, all 
correspondence, and the approved informed consent form. 
6. IRB membership list, FWA#, statement of compliance and written 
procedures pertaining to AE and protocol deviation reporting (if 
available). 
7. Study agreement, curricula vitae of investigator(s), financial disclosure, 
signature authorization log (delegation of responsibility), protocol 
signature page, and patient screening/enrollment log. 
8. Reports (including safety reports, progress reports and a final report 
from the investigator). 
9. Any other records, as required by the IRB and the sponsor. 
Reports 
Investigators are required to prepare and submit the following reports in a 
complete, accurate and timely fashion: 
1. Adverse Experiences: In the event of an adverse experience that is 
serious or unexpected, or which requires action by sponsor to prevent 
an unreasonable risk of substantial harm to public health, notice shall be 
given immediately (but in no event later than 24 hours after learning of 
such experience) by telephone, facsimile, or email to the Sponsor and 
the IRB. Any notices made by telephone shall be confirmed in writing 
within 2 days of the initial notification. The site shall provide all 
associated documentation (eg, lab reports, death summary, operative 
reports, etc.) for each adverse experience. 
2. Unexpected adverse device effects and serious adverse events should be 
reported to the sponsor within 24 hours of event discovery.  If the 
adverse event is alarming, the investigator shall report the event 
immediately. 
3. Investigators shall promptly report to the IRB all changes in the research 
activity and all unanticipated problems involving risk to participants and 
others, and that he or she will not make any changes in the research 
without IRB approval, except where necessary to eliminate apparent 
hazards to the participants. 
4. Withdrawal of IRB approval to the sponsor within 5 working days. The 
report will include a complete description of the reason that approval 
was withdrawn. 
5. Progress reports must be submitted to the IRB at regular intervals 
dictated by the IRB but no less than annually. 
6. A final report must be submitted to the IRB within 3 months after 1) 
termination or completion of the study; or 2) the investigator's work on 
the study ceases. 

 
 
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7. Any deviation from the protocol to protect the life or physical well-
being of a participant in an emergency is to be reported to the sponsor 
and IRB no later than 5 working days after the emergency occurs. 
Deviations to the informed consent process (eg, use of study product 
without informed consent) must be reported to the Sponsor and the IRB 
immediately but no later than 5 working days after the use occurs. 
Deviations from the randomization scheme must be reported to the 
sponsor as soon as possible after they are recognized. 
8. Other: upon request, the investigator will supply accurate, complete and 
current information about any aspect of the study to the sponsor. 
8.3.4 Retention of Study Records 
The sponsor must ensure that all study participant records are stored for at least 
2 years after the later of the following 2 dates: the date on which the study is 
terminated or completed (all subjects through final follow-up), or the date that 
the records are no longer required by the study site record retention policy. To 
avoid error, the site should contact the sponsor prior to the destruction of study 
records to ensure that they no longer need to be retained. In addition, the 
sponsor should be contacted if the study site is acquired or shuts down so that 
arrangements can be made for the handling or transfer of study records. 
8.3.5 Data Quality Assurance 
The sponsor, or the sponsor’s representative, may conduct audits at the study 
sites. Audits may include, but are not limited to, device supply, presence of 
required documents, the informed consent process, and comparison of eCRFs 
with source documents. The investigator agrees to participate with audits 
conducted at a reasonable time, in a reasonable manner. 
8.3.6 Confidentiality 
All information provided to investigators, IRBs, and generated in this study 
must be considered highly confidential and must not be disclosed to any persons 
not directly involved with the study without prior written permission from the 
sponsor. However, authorized regulatory officials and sponsor personnel (or 
their representatives) will be allowed full access to inspect and copy the records. 
All study products must be used solely in accordance with this protocol. Privacy 
and confidentiality of information about each participant shall be preserved in 
the reports and in any publication. Each participant in this study will be assigned 
a unique identifier. All data will be tracked, evaluated, and stored using only 
this unique identifier. 
The study site will maintain a confidential list (paper or electronic) identifying 
all participants. This list will contain the assigned participant’s unique identifier 
and name. The treating physician bears responsibility for keeping this list 
confidential. This list will not be provided to the study sponsor and is only to 
be used at the study site. 

 
 
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Monitors and auditors will have access to the study patient list and other 
personally identifying information of participants to ensure that data reported 
corresponds to the person who signed the informed consent form and the 
information contained in original source documents. Such personal identifying 
information may include, but is not limited to the participant’s name, address, 
date of birth, gender, race and medical record number. 
8.3.7 Publication Policies 
The Clinical Trial Agreement (CTA) mutually signed by the investigator(s) and 
Aerin Medical, defines and describes the nature of the study agreement. The 
data and results from this study are the sole property of Aerin Medical. Aerin 
Medical shall have the right to access and use all data and results generated 
during the clinical investigations. Publication authorship will be established 
according to ICMJE guidelines and Aerin Medical policy. Clinical study design 
will be publicly disclosed on ClinicalTrials.gov, and summary results posted 
per FDAAA 801 Requirements. Additionally, an investigator may only publish 
data generated by this trial in accordance with the terms of the Clinical Trial 
Research Agreement. 
It is Aerin Medical’s intent to encourage and facilitate the publications of 
scientifically important results, while simultaneously ensuring minimization of 
duplicative data publication and the priority publications of multicenter results 
ahead of single-center investigations. 
Aerin Medical intends to provide research sites with a standardized study report 
containing aggregated site study data. 
8.4 Early Termination 
The study can be discontinued at the discretion of the sponsor for reasons including, 
but not limited to, the following: 
• 
Obtaining new scientific knowledge that shows that the study is no longer 
valid or necessary, 
• 
Insufficient recruitment of patients, 
• 
Persistent noncompliance with the protocol. 
If the study is discontinued or suspended prematurely, the sponsor shall promptly 
inform all participating study sites and treating physicians of the termination or 
suspension and the reason(s) for the termination or suspension. The IRB shall also be 
informed promptly and provided with the reason(s) for the termination or suspension 
by the sponsor. Regulatory authorities and the personal physicians of the participants 
may also need to be informed if deemed necessary. 

 
 
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9.0 
Ethics 
9.1 Institutional Review Board 
This study may not be initiated at a site until applicable Institutional Review Board, 
or similarly named research review committee, approval is obtained. The Study 
Protocol, all Study Protocol amendments, written study participant information, 
informed consent form, and any other appropriate study-related information must be 
reviewed and approved by the IRB. 
To assure proper review and study oversight, the IRB must comply with the 
responsibilities, functions, and records requirements defined in the federal 
regulations (21 CFR Part 56). 
The investigator at each site is responsible for submitting the appropriate study 
documentation to the IRB for review and approval in accordance with federal 
regulations. The investigator is responsible for providing accurate, complete, and 
current information to the IRB throughout the course of the study. 
9.2 Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, Good Clinical Practice 
(GCP), and all applicable regulatory requirements governing clinical studies of 
marketed products. Compliance with these requirements also constitutes conformity 
with the ethical principles that have their origin in the Declaration of Helsinki. 
The sponsor will promptly review all information relevant to the safety of the product 
that is received and comply with all regulatory device safety reporting requirements. 
9.3 Participant Privacy 
The privacy of participants in this study will be protected by all reasonable means. 
The investigator is responsible for study records at the study site and must only 
disclose information as provided for in the site’s Authorization to Use and Disclose 
Health Information. Each participant must give permission for use and disclosure of 
their information by signing the Authorization to Use and Disclose Health 
Information. This form may be a separate document from the informed consent form, 
or it may be contained within or as an addendum to the informed consent form. 
Although the sponsor is not a covered entity under HIPAA, access to study records, 
particularly participant information, will be strictly limited by the sponsor to the 
investigator, the sponsor’s clinical research personnel, authorized representatives of 
the sponsor and the Food and Drug Administration under applicable federal 
regulations. No public reporting or publications of the results of this study will 
contain identifiable references to individual participants in the study. 
9.4 Participant Reimbursement 
Participants will be reimbursed for their time for completing questionnaires as 
allowed by study site policies. Participants will not be reimbursed for questionnaires 
not completed. 

 
 
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9.5 Participant Withdrawal 
Participants may withdraw from the study at any time for any reason without impact 
to their future medical care at the study site. Any participant withdrawing from the 
study for any reason will continue to receive medically necessary follow-up care as 
determined by the investigator. Every attempt should be made to follow a participant 
withdrawing either because they failed to obtain a desired effect or suffered an 
adverse event. 
When a participant chooses to withdraw, the investigator and study coordinator will 
make all possible efforts to collect and report the final visit observations. All reasons 
for withdrawals and documentation will be recorded in source documentation and the 
appropriate case report form. In addition, within the informed consent process, 
participants will be asked to provide consent for the study staff to contact them by 
mail or phone to follow up on safety-related issues as appropriate. 
9.6 Protocol Modifications 
This protocol shall not be amended without the approval of the sponsor. The sponsor 
may amend the protocol to clarify study procedures or to implement changes to the 
protocol that do not affect the validity of the data; the risk to benefit ratio; the 
scientific soundness of the protocol; or the rights, safety, or welfare of the 
participants. All modifications must be reviewed and approved by the IRB at each 
study site, or a central IRB before implementation. 
9.7 Protocol Adherence and Deviations 
The investigator(s) agree to conduct the study in accordance with this protocol. An 
investigator must not make any changes in the study without first receiving approval 
in writing from the IRB, except when necessary to eliminate apparent immediate 
hazards to a participant. Investigators will also adhere to procedures for reporting 
study deviations to their IRB in accordance with their specific IRB reporting policies 
and procedures. 
 
 

 
 
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