A Prospective, Open Label, Multi-Center Study Using the RhinAer Procedure for Treatment of Subjects Suffering With Chronic Rhinitis
Phase: NA
Conditions: Chronic Rhinitis
Sponsor: Aerin Medical

 
 
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A PRospective OpEn-Label Study usIng the RhinAer® ProcEdure for 
Treatment of Subjects SuFfering with Chronic Rhinitis - RELIEF 
Protocol Number: 
CTP1056 
Protocol Date: 
27 January 2021 
Version: 
C 
Principal Investigators: 
Jivianne Lee, MD 
 
UCLA Santa Monica Head and Neck Surgery 
1131 Wilshire Blvd, Suite 302 
Santa Monica, California 90401 
Phone: 424-259-6559  
email:jivianne@gmail.com 
 
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  
 
Sponsor Representative: 
<If the sponsor is not a resident in the country(ies) in which 
the clinical investigation is to be carried out, the name and 
address of a representative in that country (those countries) 
can be required according to national or regional 
regulations> 
 
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 Institutional Review Board, Ethics Committee, United States Food and Drug Administration or 
other regulatory agency. 
Site Name:  
 
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/Ethics Committees. 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 .................................................................................................................... 6 
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 (US) .................................................................................. 15 
2.3 
Intended Use and Indications for Use (EU) ................................................... 15 
2.4 
Rationale ........................................................................................................... 16 
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 ..................................................................................................................... 18 
4.1 
Study Design ..................................................................................................... 18 
4.2 
Study Population .............................................................................................. 18 
4.2.2 Exclusion Criteria ....................................................................................18 
4.3 
Enrollment ........................................................................................................ 19 
4.4 
Outcome Measures ........................................................................................... 19 
4.4.1 Nasal Assessment .....................................................................................19 
4.4.2 Pain – Visual Analog Scale Pain Score ..................................................20 
4.4.3 Total Nasal Symptom Score (TNSS) ......................................................20 
4.4.4 Mini Rhinoconjunctivitis Quality of Life Questionnaire 
(MiniRQLQ) .............................................................................................21 
4.4.5 Participant Satisfaction ...........................................................................22 
4.4.6 Other Rhinitis Symptoms - Cough and Postnasal Drip .......................22 
4.4.7 Change in Amount of PRN Medication/Device Use for Chronic 
Rhinitis Symptoms ...................................................................................22 
4.4.8 Medication and Other Therapies for Symptoms of Chronic 
Rhinitis ......................................................................................................22 
4.4.9 Adverse Events .........................................................................................22 
4.5 
Success/Failure Criteria .................................................................................. 22 
4.51 
Participant Success ..................................................................................23 
4.5.2 Participant Failure ...................................................................................23 
4.5.3 Study Success ............................................................................................23 
4.6 
Duration of the Study ...................................................................................... 23 
4.7 
Site Staffing and Responsibilities of Study Personnel .................................. 23 
4.8 
Device Description ........................................................................................... 23 
4.9 
Risk/Benefit Analysis ....................................................................................... 25 
4.9.1 Risks ..........................................................................................................25 
4.9.2 Mitigation of Risks ...................................................................................27 
4.9.3 Benefits ......................................................................................................27 
4.9.4 Potential Risks to Participant Confidentiality ......................................28 
4.9.5 Study Justification in Relation to Risk...................................................28 

 
 
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5.0 Study Schedule and Procedures ................................................................................. 28 
5.1 
Schedule of Events ........................................................................................... 29 
5.3 
Enrollment and Baseline Assessment ............................................................. 29 
5.4 
Treatment Visit and Procedure ...................................................................... 31 
5.5 
Postprocedure Assessments and Care ............................................................ 33 
5.6 
Follow-up Evaluations ..................................................................................... 33 
5.7 
Product Handling and Accountability ........................................................... 34 
6.0 Statistical Considerations ............................................................................................ 35 
6.1 
Study Design ..................................................................................................... 35 
6.2 
Study Hypothesis .............................................................................................. 35 
6.3 
Sample Size Estimate ....................................................................................... 35 
6.4 
Timing of Analysis ........................................................................................... 36 
6.5 
Analysis Populations ........................................................................................ 36 
6.6 
Missing Data ..................................................................................................... 36 
6.7 
Pooling ............................................................................................................... 36 
6.8 
Participant Disposition .................................................................................... 37 
6.9 
Demographics and Baseline Characteristics ................................................. 37 
6.10 
Primary Endpoint Analysis ............................................................................. 37 
6.11 
Secondary Endpoints Analysis........................................................................ 37 
6.12 
Other Outcome Measures Analyses ............................................................... 38 
6.13 
Safety Analysis ................................................................................................. 39 
6.14 
Extension Phase Analysis ................................................................................ 39 
6.15 
Standard Methods of Report .......................................................................... 40 
7.0 Adverse Events and Product Complaints .................................................................. 40 
7.1 
Adverse Events ................................................................................................. 40 
7.1.1 Definitions .................................................................................................40 
7.1.2 Documentation and Reporting of Adverse Events ................................42 
7.2 
Product Complaints ......................................................................................... 43 
7.2.1 Definitions .................................................................................................43 
7.2.2 Documentation and Reporting of Complaints ......................................44 
8.0 Study Administration .................................................................................................. 44 
8.1 
Investigator Training ....................................................................................... 44 
8.2 
Study Monitoring ............................................................................................. 44 
8.3 
Documentation of Study Findings .................................................................. 45 
8.3.1 Data Management ....................................................................................45 
8.3.2 Case Report Forms ..................................................................................45 
8.3.3 Investigator Responsibilities, Records, and Reports ............................47 
8.3.4 Retention of Study Records.....................................................................49 
8.3.5 Data Quality Assurance ...........................................................................49 
8.3.6 Confidentiality ..........................................................................................49 
8.3.7 Publication Policies ..................................................................................49 
8.4 
Study Suspension or Early Termination ....................................................... 50 
9.0 Ethics ............................................................................................................................. 50 
9.1 
Institutional Review Board/Ethics Committee .............................................. 50 
9.2 
Ethical Conduct of the Study .......................................................................... 51 

 
 
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9.3 
Participant Privacy .......................................................................................... 51 
9.4 
Participant Reimbursement ............................................................................ 51 
9.5 
Participant Insurance ...................................................................................... 51 
9.6 
Participant Withdrawal................................................................................... 52 
9.7 
Protocol Modifications..................................................................................... 52 
9.8 
Protocol Adherence and Deviations ............................................................... 52 
9.8.1 Definition ..................................................................................................52 
9.8.2 Documentation and Reporting of Deviations ........................................52 
10.0 References ..................................................................................................................... 54 

 
 
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Protocol Summary 
Title of Study: 
A PRospective OpEn-Label MuLticenter Study usIng the RhinAer® 
ProcEdure for Treatment of Subjects SuFfering with Chronic Rhinitis - 
RELIEF 
Purpose: 
The purpose of this study is to assess the clinical use of the RhinAer 
Stylus to treat tissue in the posterior nasal nerve area to improve 
symptoms in adults diagnosed with chronic rhinitis.  
Indications for 
Use (United 
States):  
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. 
Intended and 
Indications for 
Use (European 
Union): 
The RhinAer Stylus is intended to improve nasal breathing by modifying 
the soft tissues of the nasal airway. It 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. Device has CE Marking in EU. 
The Aerin Console is an electrosurgical system intended to generate 
radiofrequency (RF) electrical current for modification of soft tissues 
during ear, nose and throat procedures, when used with an Aerin Medical 
Stylus. It is indicated for use in delivering radio-frequency energy to 
tissues as part of ear, nose and throat procedures 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 both nostrils treated in the portion of the 
nasal cavity mucosa overlying the region of the posterior nasal nerve 
(the posterior middle meatus and posterior inferior meatus) during a 
single study procedure session. Each nasal cavity 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. 
Study Design: 
The study is designed as a multicenter (up to 20 sites), prospective, open-
label, single-arm study. 

 
 
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All participants will be evaluated prior to treatment and following 
treatment at 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 26 weeks (6 months), 52 weeks (12 months), 104 weeks 
(24 months) and 156 weeks (36 months) to provide additional 
information on longer-term efficacy and duration of treatment effect. 
Study 
Objective: 
The primary objective is to assess the performance of the RhinAer 
procedure with respect to mean change in the 24-hour reflective Total 
Nasal Symptom Score (rTNSS) at 3 months posttreatment when used as 
a treatment for chronic rhinitis. A secondary objective is the evaluation 
of treatment effect duration through an extended follow-up to 36 months. 
Primary 
Endpoint: 
Mean change in the 24-hour rTNSS from baseline to 3 months after the  
study procedure.   
Secondary 
Endpoints: 
• Participant responder percentage, defined as the proportion of 
participants achieving a successful outcome at the 3-month 
evaluation. A successful outcome is defined as a 30% improvement 
(decrease) in the rTNSS. 
• Mean change in the Mini Rhinoconjunctivitis Quality of Life 
Questionnaire (MiniRQLQ) score from baseline to 3 months after 
the study procedure. 
• Frequency of device-related and procedure-related serious adverse 
events through the 3-month evaluation. 
Other 
Outcome 
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, following the treatment 
procedure and at 3 months. 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 (0 indicating no pain and 100 
indicating the worst pain ever) assessed posttreatment and at 3 months. 
rTNSS:  
• rTNSS mean and change from baseline at the 3-, 6-, 12-,  24- and 
36-month follow-up evaluations. 
• rTNSS Individual Nasal Symptom Scores (rhinorrhea, nasal 
congestion, nasal itching, and sneezing) at baseline and at the 3-, 6-, 
12-, 24-month and 36-month follow-up evaluations. 

 
 
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• Proportion of responders based on improvement in rTNSS at the 3-, 
6-, 12-,24-and 36-month follow-up evaluations. 
MiniRQLQ: 
• MiniRQLQ mean and change from baseline at the 3-, 6-, 12-, 24-, 
and 36-month follow-up evaluations. 
• MiniRQLQ domain scores (activity limitations, practical problems, 
nose symptoms, eye symptoms, and other symptoms) at baseline 
and the 3-, 6-, 12-, 24-, and 36-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-, 24-, and 36-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-, 24-, and 36-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-, 24-, and 36-month follow-up evaluations. 
Medications - Medications associated with relief or treatment of nasal 
airway obstruction 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. 
Length of 
Study: 
The primary outcome will be evaluated at 3 months. In addition, 
evaluations at 6, 12, 24, and 36 months after treatment will extend 
follow-up to 3 years for evaluation of longer-term efficacy. Enrollment 
is anticipated to be completed within 6 months. Therefore, total study 
duration is anticipated to be approximately 42 months. 
Study Centers: 
up to 20  
 
Participants: 
Up to 140 subjects 
 
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. 

 
 
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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. 
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 
In office 
Remote 
  Procedure 
  Immediate 
Postprocedure 
  3 Months1  
  (13 weeks) 
  6 Months 
  (26 weeks) 
 12 Months 
 (52 weeks) 
 24 Months 
 (104 weeks) 
 36 Months 
 (156 weeks) 
Window (days) 
(-30) 
(0) 
(0) 
(± 14) 
(± 30) 
(± 30) 
(± 30) 
(± 30) 
Activity / Assessment 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
Nasal assessment (physical, endoscopic) 
X 
X 
X 
X 
 
 
 
 
Current medication use (study relevant) 
X 
X 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
 
 
 
 
 
 
 
VAS nasal pain  
 
 
X 
X 
 
 
 
 
Rhinitis symptoms (rTNSS, cough, and 
postnasal drip)  
X 
 
 
X 
X 
X 
X 
X 
MiniRQLQ 
X 
 
 
X 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
1Primary analysis endpoint. 
 
 
 
 
 
 
 
 

 
 
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List of Abbreviations 
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 
EC – Ethics Committee 
EDC – Electronic data capture 
ENT – Ear, Nose, Throat; medical field of otorhinolaryngology (otolaryngology) 
EU – European Union 
FDA – Food and Drug Administration (US) 
FWA – Federalwide Assurance for the Protection of Human Subjects 
GCP – Good Clinical Practice 
ICH – International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICMJE – International Committee of Medical Journal Editors 
IFU – Instructions for Use 
IRB – Institutional Review Board 
ISO – International Organization for Standardization 
MCID – minimal clinically important difference 
MDD – Medical Device Directive 
MiniRQLQ – Mini Rhinoconjunctivitis Quality of Life Questionnaire  

 
 
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NAR – nonallergic rhinitis 
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 percent for at least 
a 1-point improvement in rTNSS at 12 weeks was 94%. Responder percent, 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 

 
 
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relatively mild, 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. 
2.0 
Purpose 
The purpose of this study is to assess the clinical use of the RhinAer Stylus to treat 
tissue in the posterior nasal nerve area to improve symptoms in adults diagnosed with 
chronic rhinitis. 
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 United States (US) by the Food and 
Drug Administration (FDA) under 510(k) K192471 and the Aerin Console was 
cleared under 510(k) K162810. The RhinAer Stylus is has CE Marking in the 
European Union (EU). The Aerin Console has CE Marking in the EU. 
2.2 Indications for Use (US) 
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 Intended Use and Indications for Use (EU) 
The RhinAer Stylus is intended to improve nasal breathing by modifying the soft 
tissues of the nasal airway. It 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. RhinAer Stylus has CE Marking 
in the EU. 
The Aerin Console is an electrosurgical system intended to generate radiofrequency 
(RF) electrical current for modification of soft tissues during ear, nose and throat 
procedures, when used with an Aerin Medical Stylus. It is indicated for use in 
delivering radio-frequency energy to tissues as part of ear, nose and throat procedures 
in small clinic, office or hospital environments. 

 
 
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2.4 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. 
3.0 
Study Objectives 
3.1 Primary Objective 
The primary objective is to assess the performance of the RhinAer procedure with 
respect to improvement in the rTNSS from baseline to 3 months when used as a 
treatment for chronic rhinitis. 
The primary objective will be assessed through evaluation of the primary endpoint 
defined as comparison of the mean rTNSS at baseline to the mean rTNSS at 3 months 
postprocedure. 
3.2 Secondary Objectives 
Additional objectives include assessment and comparison of secondary endpoints and 
informational outcome measures. 
Secondary endpoints are: 
• Participant responder percentage at 3 months. Individual participant success 
(responder) is defined as at least 30% improvement (decrease) in the 24-
hour reflective Total Nasal Symptom Score (rTNSS). 
• Mean change in the Mini Rhinoconjunctivitis Quality of Life Questionnaire 
(MiniRQLQ) score from baseline to 3 months after the study procedure. 
• 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 PNN 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. 

 
 
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• 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-, 24-, and 36-
month follow-up evaluations. 
o rTNSS Individual Nasal Symptom Scores (rhinorrhea, nasal 
congestion, nasal itching, and sneezing) at baseline and the 3-, 6-, 12-, 
24-, and 36-month follow-up evaluations. 
o Proportion of responders based on improvement in rTNSS at the 3-, 
6-, 12-, 24-, and 36-month follow-up evaluations. 
• MiniRQLQ:  
o MiniRQLQ mean and change from baseline at the 3-, 6-, 12-, 24-, and 
36-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-, 24-, and 36-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-, 24-, and 36-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-, 24-, and 36-
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-, 24-, and 36-
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 will be evaluated with respect 
to overall incidence of adverse events and treatment-related adverse events. 

 
 
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4.0 
Study Plan 
4.1 Study Design 
The study is designed as a multicenter (up to 20 sites), prospective, open-label, 
single-arm study in up to 140 participants. 
All participants will be evaluated prior to treatment and following treatment at week 
13 (3 months). The 3-month evaluation will occur in the physician’s office and be 
used for the primary analysis. 
The study will have additional follow-up evaluations at 6, 12, 24, and 36 months 
conducted by phone interview 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.  

 
 
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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. 
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. 
4.3 Enrollment 
Patients diagnosed with chronic rhinitis and meeting all eligibility criteria may be 
enrolled in the study. 
4.4 Outcome Measures 
4.4.1 Nasal Assessment 
The target PNN area within each nostril will be visually assessed at baseline 
(pretreatment), immediately following the treatment procedure, and at 3-month 
evaluation. 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 

 
 
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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. 
4.4.2 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 
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. 
4.4.3 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 has cited the TNSS 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 

 
 
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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. 
4.4.4 Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) 
The Rhinoconjuctivitis Quality of Life Questionnaire 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 

 
 
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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 
4.4.5 Participant Satisfaction 
Satisfaction with the procedure is measured with a 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  
4.4.6 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) 
• 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). 
4.4.7 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.  
4.4.8 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. 
4.4.9 Adverse Events 
Adverse events will be documented according to Section 7.1. 
4.5 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 change in mean rTNSS from 
baseline to 3 months after the procedure. 

 
 
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4.51 
Participant Success 
The 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. 
4.5.2 Participant Failure 
A participant will be considered a nonresponder at the 3-month evaluation if 
the success criterion has not been attained. 
4.5.3 Study Success 
The study will be considered a success if the mean change from baseline of the 
rTNSS at 3 months significantly exceeds the MCID set for the study.  
4.6 Duration of the Study 
The primary outcome will be evaluated at 3 months. In addition, evaluations at 6, 12, 
24, and 36 months after treatment will extend follow-up to 3 years for evaluation of 
longer-term efficacy. Enrollment is anticipated to be completed within 6 months. 
Therefore, total study duration is anticipated to be approximately 42 months. 
4.7 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.  
The treating physician will perform the procedure and discharge and 3-month follow-
up assessments. The treating physician must be a medical doctor with experience in 
ENT procedures and trained in administering the RhinAer procedure. 
Remote follow-up will be performed by 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.  
4.8 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. RhinAer has CE Marking in EU. 
The Aerin Console (Model FG226) RF generator with temperature control capable 
of delivering very low doses of energy was cleared for use in the US (FDA - 
K162810) and has CE Marking in the EU (CE639608)  
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 

 
 
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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 PNN 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 PNN 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. 
 
 
 
Figure 1.  RhinAer Stylus 
 
 
 

 
 
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Figure 2.  RhinAer Stylus tip 
 
 
 
Figure 3.  Aerin Console with RhinAer Stylus 
4.9 Risk/Benefit Analysis 
4.9.1 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, 

 
 
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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) 
• 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 

 
 
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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. 
4.9.2 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 
enrollment. 
• 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 IRB(s)/EC(s) and 
conducted according to applicable regulations with ongoing review by 
the IRB/EC. 
• 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 Console has been cleared for use in the US by the FDA based in 
part on prior clinical studies demonstrating safety and efficacy of its use 
and CE Marking in the EU. The RhinAer Stylus is also cleared for use 
by the FDA based in part on prior clinical studies demonstrating safety 
and efficacy of use, and has CE Marking in the EU. 
4.9.3 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 PNN 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 

 
 
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destruction of tissue in PNN 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.  
4.9.4 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 electronic data capture (EDC) system through the study’s electronic 
case report forms (eCRF). Risks to participant confidentiality are further 
minimized by allowing only 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. 
4.9.5 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. 

 
 
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5.1 Schedule of Events 
 
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. 
 
Screening 
Treatment 
Follow-up 
In office 
Remote 
  Procedure 
  Immediate 
Postprocedure 
  3 Months1  
  (13 weeks) 
  6 Months 
  (26 weeks) 
 12 Months 
 (52 weeks) 
 24 Months 
 (104 weeks) 
 36 Months 
 (156 weeks) 
Window (days) 
(-30) 
(0) 
(0) 
(± 14) 
(± 30) 
(± 30) 
(± 30) 
(± 30) 
Activity / Assessment 
 
 
 
 
 
 
 
 
Eligibility 
X 
 
 
 
 
 
 
 
Consent 
X 
 
 
 
 
 
 
 
Demographics / Medical History 
X 
 
 
 
 
 
 
 
Physician Evaluations 
 
 
 
 
 
 
 
 
Nasal assessment (physical, endoscopic) 
X 
X 
X 
X 
 
 
 
 
Current medication use (study relevant) 
X 
X 
X 
X 
X 
X 
X 
X 
Participant Evaluations 
 
 
 
 
 
 
 
 
VAS nasal pain  
 
 
X 
X 
 
 
 
 
Rhinitis symptoms (rTNSS, cough, and 
postnasal drip)  
X 
 
 
X 
X 
X 
X 
X 
MiniRQLQ 
X 
 
 
X 
X 
X 
X 
X 
Participant Satisfaction Survey 
 
 
 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
1Primary analysis endpoint. 
 
 
 
 
 
 
 
 

 
 
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Informed consent 
Informed consent must be obtained in accordance with FDA regulation 21 CFR 
Part 50 and ISO 14155. The clinical investigator or designated staff member is 
responsible for ensuring that IRB/EC approved informed consent is obtained for 
each participant prior to participation in the study or before undergoing any 
procedure specific to the clinical investigation. The patient must be fully 
counseled with an explanation of the study background, 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. Any new 
information obtained during the course of the study that may affect the health of 
the participant or their decision to continue in the study will be provided to the 
participant. 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: 
• answer the participant’s questions, 
• 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. 
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 

 
 
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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 the eCRF.  
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.  
The MiniRQLQ will be completed by the participant on the MiniRQLQ CRF. 
5.4 Treatment Visit and Procedure 
If the participant meets eligibility criteria and signs the IRB/EC approved informed 
consent the participant is considered enrolled.  
The treatment procedure is summarized below. Consult the RhinAer Stylus and Aerin 
Console Instructions for Use (IFUs) for full detail of the treatment procedure and 
step-by-step instructions for preparation and use of the RhinAer Stylus and Aerin 
Console. 
Preparation  
The procedure will be performed in the study clinic. The participant will be in a 
reclined or supine position on the procedure table. A visual physical and endoscopic 
nasal assessment will be conducted just prior to the procedure and 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 PNN 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). 

 
 
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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 a minimum of 20 minutes, and 
then inject anesthesia to the treatment area after initial numbness has occurred. 
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 
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.  
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 

 
 
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• 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. 
Participants should have their 3-month follow-up visit (13 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 
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). The office follow-up evaluation occurs at 13 weeks 
after the procedure. Evaluations at 6, 12, 24, and 36 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 
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All participants should be followed through the final evaluation visit at 3 years 
postprocedure regardless of their success/failure classification at previous 
evaluations. 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: 
Office evaluation at 13-week (3-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) 
• rTNSS (completed by participant) 
• Cough and postnasal drip symptoms (completed by participant) 
• MiniRQLQ (completed by participant) 
• VAS pain score (completed by participant)  
• Adverse events. 
Remote (telephone) evaluations: 6-month (26-week), 12-month (52-week), 24-month 
(104-week), and 36-month (156-week) follow-up  
• rTNSS (verbal administration by site personnel) 
• Cough and postnasal drip symptoms (verbal administration by site personnel) 
(no 2-week) 
• 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). 
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 

 
 
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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 
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, open-label, single-arm study to assess the 
performance of the RhinAer procedure for treatment of chronic rhinitis. The study is 
designed to assess improvement in rTNSS and other measures from baseline 
condition to 3 months after the procedure, as well as for extended follow-up through 
3 years.  
6.2 Study Hypothesis 
The primary endpoint of the study is change in mean rTNSS from baseline to the 13-
week evaluation.  Improvement in the rTNSS is represented by a decrease from 
baseline in the 12-point score. 
An MCID of 1 unit, or 2 to 4 times the more rigorously derived MCIDs, was set for 
this study. The hypothesis is that the improvement (decrease) in rTNSS mean score, 
measured as change from baseline at 13 weeks (13 weeks - baseline), exceeds the 
MCID (1 unit). 
The null (H0) and alternative (HA) hypotheses are:  
H0: µd ≥ -1 
HA: µd < -1 
where µd = the mean change of the paired differences of the 13-week scores minus 
the baseline scores. 
Rejection of the null hypothesis in favor of the alternative (HA) hypothesis means that 
there is evidence for a clinically significant improvement (decrease) in the rTNSS. 
6.3 Sample Size Estimate 
The study will enroll up to 140 participants. The power analysis was performed such 
that there is adequate power to reject the null hypothesis that the mean improvement 
from baseline in rTNSS is 1 point or less. Sample size estimation was based on a 
paired t-test for change from baseline at 13 weeks using the following assumptions: 
• Significance level α = 0.025 (one-sided) 
• Power = 90% 
• µd = 1-point decrease in mean change score = MCID  
• SD = 3 = estimated standard deviation of the mean difference based on an 
observed SD of 2.6 in a prior study. 

 
 
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The minimum number of subjects to achieve 90% power is 97 (G-Power, paired t-
test). Allowing for 15% loss (nonevaluable) and adjusting for a balanced distribution 
across 20 sites the sample size is 140 participants. 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. 
6.5 Analysis Populations 
Enrolled Population – all subjects enrolled in the study. 
Evaluable Population – all subjects that are enrolled in the study and have received 
the study procedure. 
Safety Population – all subjects enrolled in the study. 
6.6 Missing Data 
All efforts will be made to collect all data points in this study. Missing data will be 
imputed for the primary endpoint by assuming the missing outcomes represent no 
change from baseline. Additional post hoc sensitivity analyses may be performed if 
missing cases exceed 10% of the sample size, including a worst-case analysis (all 
missing rTNSS at 3 months are the worst possible score), to further 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). Pooling 
is generally justified because the study will be conducted such that: 1) the same 
protocol will be used at each site; 2) site investigators and personnel will receive 
uniform training; and 3) central data management and monitoring will be consistent 
and applied with equal rigor at all sites. Comparability between study sites may be 
shown using summary statistics calculated by site. 

 
 
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6.8 Participant Disposition 
A detailed description of participant disposition will be provided using a CONSORT 
diagram and summaries of participants falling in various subgroups of interest, such 
as, enrolled but not treated, discontinued, protocol deviations, deaths, and 
withdrawals. All study population exclusions and reasons will be summarized. 
Follow-up by visit will be presented, showing theoretical, expected, and actual 
follow-up visits. 
6.9 Demographics and Baseline Characteristics 
Demography and other baseline characteristics 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. 
Baseline covariates with possible impact on outcomes at 3 months are: 
• Age  
• Race 
• Sex 
• BMI 
• Allergic status (allergic rhinitis - nonallergic rhinitis). 
Results may be evaluated by allergic status if sufficient numbers are obtained in both 
categories. 
6.10 Primary Endpoint Analysis 
The mean change in the rTNSS from baseline to 13 weeks will be tested using a 
paired t-test for a significant decrease greater than the MCID under the one-sided null 
and alternative hypotheses. 
A P value for the test statistic ≤.025 will indicate that the mean decrease is statistically 
significantly greater than 1 point.  The upper limit of the one-sided 97.5% confidence 
interval on the mean decrease will also be calculated. 
6.11 Secondary Endpoints Analysis 
Secondary endpoints will be formally tested only after the primary objective of the 
study is met. Confidence intervals (95%) will be included for all secondary outcome 
measures. 
• Responder percentage at 13 weeks 
The proportion of responders will be calculated along with the 95% 
confidence interval. Individual participant success (responder) is defined as 
at least 30% improvement (decrease) in the 24-hour reflective Total Nasal 
Symptom Score (rTNSS). An overall responder percent of at least 60% is 

 
 
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expected for the study. The observed proportion of responders will be 
compared to the expected proportion with a binomial test. 
• Mean change in the Mini Rhinoconjunctivitis Quality of Life Questionnaire 
(MiniRQLQ) score from baseline to 13 weeks after the study procedure. 
The mean change in the MiniRQLQ score from baseline to 13 weeks will 
be tested using a paired t-test for a significant decrease greater than the 
MCID. 
• Device-related and procedure-related serious adverse events through 13 
weeks 
The proportions of serious device-related adverse events through 13 weeks 
will be calculated along with the 95% confidence interval. 
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 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 or mixed effects modeling 
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 at baseline, just 
prior to treatment, immediately after treatment, and at 3 months after the 
procedure.   
• Visual analog scale (VAS) for pain - Summary will include mean VAS pain 
scores assessed posttreatment and at 3 months. 
• 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-, 24-, and 36-
month follow-up evaluations. 
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-, 24-, and 36-
month follow-up evaluations. 

 
 
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o Proportion of responders based on 30% improvement in rTNSS at 
the 3-, 6-, 12-, 24-, and 36-month follow-up evaluations. 
• 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-, 24-, and 36-month follow-up evaluations. 
• 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-, 
24-, and 36-month follow-up evaluations. 
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-, 
24-, and 36-month follow-up evaluations. 
• Participant satisfaction assessment - mean response for each of the 5 survey 
questions will be summarized at the 3-, 6-, 12-, 24-, and 36-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 for the 3-, 6-, 12-, 24-, and 36-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 
will be provided. Medication use by categories may also be presented as 
percentages of participants.  
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 

 
 
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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 follow-up. 
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 users or other persons, whether or not related to the 
investigational medical device and whether anticipated or unanticipated (ISO 
14155).  
Serious Adverse Event (SAE) -  an adverse event that led to any of the following 
(ISO 14155): 
a) Death, 
b) Serious deterioration in the health of the subject, users or other persons 
as defined by one or more of the following: 
1) a life-threating illness or injury, or 
2) a permanent impairment of a body structure or a body function 
including chronic disease, or 
3) in-patient or prolonged hospitalization, or  
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body 
function, 
c) fetal distress, fetal death, or a congenital abnormality, or birth defect 
including physical or mental impairment 
Note: Planned hospitalization for a pre-exiting condition, or a procedure 
required by the protocol, without serious deterioration in health, is not 
considered a serious adverse event.  

 
 
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Adverse Device Effect (ADE) - Adverse event related to the use of an 
investigational medical device.  
Note: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device. This 
definition also includes any event resulting from use error or from intentional 
misuse of the investigational medical device (ISO 14155). 
Serious Adverse Device Effect (SADE) - an adverse device effect that has 
resulted in any of the consequences characteristic of a serious adverse event 
(ISO 14155) 
Unanticipated (Serious) Adverse Device Effect (UADE or USADE) - any 
serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death 
was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects (21 CFR 812.3(s)). 
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 procedure. 
• Unlikely 
The relationship with the use of the device or procedure seems not 
relevant and/or the adverse event can be reasonably explained by 
another cause, but additional information may be obtained.  
• 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 
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. 

 
 
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• 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 will be monitored from the time of enrollment through study 
exit. All adverse events must be reported on the Adverse Event Report eCRF. 
A description of the event, including onset date, resolution date, action taken, 
and the outcome should be provided. All adverse events will be followed until 
they are adequately resolved or reach a chronic, stable state. If a participant 
reaches the 36-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 

 
 
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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/EC 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 [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. [ISO 13485:2016]  
Reportable Complaint – Any product complaint that represents an event, which 
must be reported to a regulatory agency including: 
• US FDA (21 CFR Part 803) 
• A Competent Authority within the European Community or a Notified 
Body (MDD) 
• The Canadian HPFB 

 
 
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• Any regulatory agency, within the country of distribution. 
Device Deficiency – inadequacy of a medical device with respect to its 
identity, quality, durability, reliability , usability, safety or performance. 
Note: Device deficiencies include malfunctions, use errors, and inadequacy in 
the information supplied by the manufacturer including labeling. This 
definition includes device deficiencies related to the investigational medical 
device or the comparator (ISO 14155) 
7.2.2 Documentation and Reporting of Complaints 
All product complaints, deficiencies, and malfunctions associated with devices 
will be documented on the appropriate eCRF 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 ICH E6 Good Clinical 
Practice, Abbreviated Requirements of 21 CFR 812 for nonsignificant risk device 
studies, ISO 14155, the Declaration of Helsinki, the Belmont Report, and any 
applicable regional or national regulations.  
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 investigator shall act in accordance the applicable standards, guidelines and 
regulations. 
This study is funded by Aerin Medical. The Clinical Trial Agreement (CTA), mutually 
signed by the study site and Aerin Medical, describes the agreement between sponsor 
and site with respect to study financing. 
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, monitoring logistics, and regulatory requirements. 
8.2 Study Monitoring 
Study monitoring will be carried out in compliance with FDA regulations, ISO 
14155, and GCP guidelines. The monitoring for this study will be carried out by 

 
 
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monitors qualified by experience and training who are Aerin Medical employees or 
individuals contracted by Aerin to conduct monitoring activities. The study monitors 
will oversee the conduct of the study and evaluate compliance with the protocol, any 
specific recommendations made by the site’s IRB/EC, and the signed Investigator 
Agreement. During the study, phone contacts and site visits will be conducted to 
ensure protocol compliance. Monitoring will include verification the informed 
consent was properly obtained for all study participants, a review of the clinical 
records for accuracy and completeness, resolution of missing or inconsistent results, 
a review of source documents, and ensuring adverse events, protocol deviations and 
device usage are properly documented. The monitor will conduct source data 
verification by verifying eCRFs are consistent with source documents. The 
investigator will make available to the monitor for review the informed consent 
forms, source documents, and any other relevant records for all study participants at 
the site. The investigator and other site personnel will be accessible to the monitor 
during visits and sufficient time is provided to conduct the visits and address 
questions. If the monitor becomes aware of any deficiencies during the course of the 
study, the monitor will discuss with the sponsor and investigator to ensure 
compliance is maintained. A final close-out monitoring visit will occur when the 
study has been completed or terminated.   
8.3 Documentation of Study Findings 
8.3.1 Data Management 
A secure EDC and data 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. Investigators are responsible for accurate 
completion and timely submission of the data collected during the study. Sites 
will be trained in the use of the system for entering study data and uploading 
supporting documents and will be given access for this purpose. Data 
monitoring will be performed to identify missing data, verify data accuracy and 
ensure queries are resolved. Any data issues are to be promptly addressed with 
the investigator. Quality assurance procedures will be established to ensure that 
complete, accurate and timely data are submitted, protocol requirement are 
followed, and that complications, adverse events and adverse device effects are 
correctly reported and investigator as appropriate. The management and 
retention of these data will be compliant with applicable regulatory 
requirements. 
8.3.2 Case Report Forms 
Standardized eCRFs will be used at all participating study sites to collect 
complete and accurate records of the clinical data. 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.  

 
 
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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) 
• Medication Log (14) 
 
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† 
13-Week office) 
±14 
03, 04, 06A, 06B, 11 
Nasal assessment images† 
6-Month (Remote) 
±30 
03, 04, 11, 13 
 
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. 
 

 
 
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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/EC 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), or 
other documentation as required by the IRB/EC and national regulations. 
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/EC, the 
sponsor, the study monitors, other investigators, and regulatory 
agencies. 
2. Device accountability records that will track device usage for all study 
participants. Information tracked will include date of receipt, lot or 
serial number, date of usage, participant ID and disposition of all study 
products, including the type and quantity of the product, the dates of 
their return, if applicable, the occurrence of any device malfunctions, 
and initials of study personnel conducting the device accountability. 
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. 
5. IRB/EC records, including original and ongoing study approvals, all 
correspondence, and the approved informed consent form. 
6. IRB/EC membership list, FWA# as applicable, 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/EC and the sponsor. 

 
 
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Reports 
Investigators are required to prepare and submit the following reports in a 
complete, accurate and timely fashion: 
1. 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/EC. 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/EC 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/EC approval, except where necessary to 
eliminate apparent hazards to the participants. 
4. Withdrawal of IRB/EC 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/EC at regular intervals 
dictated by the IRB/EC but no less than annually. 
6. A final report must be submitted to the IRB/EC within 3 months after 
1) termination or completion of the study; or 2) the investigator's work 
on the study ceases. 
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/EC 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/EC immediately but no later than 5 working days after the use 
occurs. 
8. Other: upon request, the investigator will supply accurate, complete and 
current information about any aspect of the study to the sponsor. 

 
 
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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/ECs, 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. 
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 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 

 
 
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access and use all data and results generated during the clinical investigations. 
Publication authorship will be established according to International Committee 
of Medical Journal Editors (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 CTA. 
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 Study Suspension or Early Termination 
The study can be suspended or 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, 
• 
Unanticipated adverse device effect presenting an unreasonable risk to the 
patients, 
• 
Persistent noncompliance with the protocol and/or IRB/EC or regulatory 
authority requirements. 
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/EC shall 
also be informed promptly and provided with the reason(s) for the termination or 
suspension by the sponsor. The investigator shall promptly inform enrolled 
participants at his/her study site, if appropriate. Regulatory authorities and the 
personal physicians of the participants may also need to be informed if deemed 
necessary. All applicable study documents will be subject to the same retention policy 
as detailed in Section 8.3.4. 
9.0 
Ethics 
9.1 Institutional Review Board/Ethics Committee 
This study may not be initiated at a site until applicable Institutional Review 
Board/Ethics Committee, or regulatory authority approval/favorable opinion 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/EC. Any additional 
requirements or conditions imposed by the IRB/EC or regulatory authority shall be 
followed, if appropriate.  

 
 
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To assure proper review and study oversight, the IRB/EC must comply with the 
responsibilities, functions, and records requirements defined in the federal 
regulations (21 CFR Part 56) or per their regulatory authority. 
The investigator at each site is responsible for submitting the appropriate study 
documentation to the IRB/EC for review and approval in accordance with federal 
regulations. The investigator is responsible for providing accurate, complete, and 
current information to the IRB/EC 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 and 
the rights, safety and well-being of study subjects shall be protected consistent with 
these principles. 
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, or in accordance with EC policies and national regulations. Each 
participant must give permission for use and disclosure of their information by 
signing the Authorization to Use and Disclose Health Information or documents as 
required by the EC and/or regulatory authority. 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 FDA under applicable 
federal regulations or other regulatory authority as required per national 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 the IRB/EC and study site policies. Participants will not be reimbursed 
for questionnaires not completed. 
9.5 Participant Insurance 
It is the responsibility of the sponsor to provide insurance covering the cost of 
treatment of participants in the event of clinical-investigation-related injuries, in 
accordance with the national regulations, as applicable. 

 
 
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9.6 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. In addition, the investigator may 
withdraw a participant from the study, if in the investigator’s opinion, it is not in the 
best interest of the participant to continue in the study. 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. If the 
investigator has made 3 documented attempts to contact the participant and received 
no response, the participant may be considered to be lost to follow-up. A participant 
who misses a study visit but attends a subsequent visit will no longer be considered 
lost to follow-up.  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. 
9.7 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/EC at each 
study site, or a central IRB before implementation. 
9.8 Protocol Adherence and Deviations 
9.8.1 Definition 
Deviation – instance of failure to follow, intentionally or unintentionally, the 
requirements of the protocol (ISO 14155). 
9.8.2 Documentation and Reporting of 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/EC, except when necessary to eliminate 
apparent immediate hazards to a participant. Investigators will also adhere to 
procedures for reporting study deviations to their IRB/EC in accordance with 
their specific IRB/EC reporting policies and procedures. Deviations will also 
be reported to the regulatory authority as required per national regulations. 
Deviations must be reported to the sponsor regardless of whether medically 
justifiable, pre-approved, or performed to protect the participant in an 
emergency. The investigator will document and explain the reason for the 

 
 
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deviation. Participant-specific deviations will be reported using the Protocol 
Deviation eCRF.  
 
 

 
 
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