Feasibility Study of Multi-Treatment Posterior Nasal Nerve (PNN) Modulation for Treatment of Chronic Rhinitis
Phase: NA
Conditions: Chronic Rhinitis
Sponsor: Arrinex, Inc.

 
Confidential 
 
 
Feasibility Study of Multi-Treatment Posterior Nasal Nerve 
Modulation for Treatment of Chronic Rhinitis 
 
 
Protocol Number: CT-0005 
Version Number:  1.0 
Version Date: 30 October 2018 
 
Principal Investigator: 
 
David M. Yen, MD, FACS 
Sponsor: 
 
Arrinex, Inc. 
Sponsor Contact: Meredith Mundy 
1755 E. Bayshore Rd., Suite 26B 
Redwood City, CA 94063 
Phone: 408-440-7049 
Email: meredith.mundy@arrinex.com 
 
 
 
 

 
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Summary of Changes from Previous Version: 
CIP 
Version 
Rev. 
CIP Date 
Summary of Revisions Made 
1.0 
A 
30 Oct 2018 
Initial Release 
 

 
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STUDY CONTACTS 
 
Study Manager 
Data Management 
Meredith Mundy 
Director, Clinical Operations 
Arrinex, Inc. 
Phone: (408) 440-7049 
Email: meredith.mundy@arrinex.com 
 
Ronald Pang 
Sr. Clinical Data Manager 
Arrinex, Inc. 
Phone: (650) 594-1160 
Email: ronald.pang@arrinex.com 
Principal Investigator 
Independent Imaging Physician Reviewer 
David M. Yen, MD, FACS 
Specialty Physician Associates 
Phone: (610) 737-7428 
Email: yen_dm@yahoo.com 
 
David Conley, MD 
Associate Professor of Otolaryngology – Head & 
Neck Surgery 
Feinberg School of Medicine 
Northwestern University 
Email:  dconley@nm.org 
 
 
 

  
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Table of Contents 
Study Contacts ........................................................................................................................................................... iii 
STATEMENT OF COMPLIANCE & INVESTIGATOR SIGNATURE PAGE ...................................................... 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schema ................................................................................................................................................. 2 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 3 
2 
INTRODUCTION ............................................................................................................................................ 4 
2.1 
Study Rationale .................................................................................................................................... 4 
2.2 
Background........................................................................................................................................... 4 
2.3 
Report of Prior Investigations............................................................................................................. 5 
2.4 
Device Description ............................................................................................................................... 7 
2.5 
Risk/Benefit Assessment .................................................................................................................... 8 
2.5.1 
Known Potential Risks ..................................................................................................... 8 
2.5.2 
Known Potential Benefits ................................................................................................ 9 
2.5.3 
Assessment of Potential Risks and Benefits ................................................................ 9 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 9 
4 
STUDY DESIGN ............................................................................................................................................. 9 
4.1 
Overall Design ...................................................................................................................................... 9 
4.2 
End of Study Definition ..................................................................................................................... 10 
5 
STUDY POPULATION ................................................................................................................................ 10 
5.1 
Inclusion Criteria ................................................................................................................................ 10 
5.2 
Exclusion Criteria ............................................................................................................................... 10 
5.3 
Screen Failures .................................................................................................................................. 11 
5.4 
Strategies for Recruitment and Retention ...................................................................................... 11 
6 
STUDY TREATMENT .................................................................................................................................. 11 
6.1 
Study Treatment Administration ...................................................................................................... 11 
6.2 
Device Acquisition and accountability ............................................................................................ 12 
6.3 
Concomitant Medications ................................................................................................................. 12 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 13 
7.1 
Participant Discontinuation/Withdrawal from the Study ............................................................... 13 
7.2 
Lost to Follow-Up ............................................................................................................................... 13 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 14 
8.1 
Study Procedures .............................................................................................................................. 14 
8.1.1 
Screening Visit (Visit 1) (DAy -30 to 0) ....................................................................... 14 
8.1.2 
Baseline Visit (Visit 2) (Day -7 to 0) ............................................................................. 14 
8.1.3 
Treatment Visit (Visit 3) (Day 0) ................................................................................... 15 
8.1.4 
7-Day Follow-up Visit (Visit 4) (Day 7) ........................................................................ 15 
8.1.5 
1-Month Follow-up Visit (visit 5) (Day 30) .................................................................. 16 
8.1.6 
3-Month Follow-up visit (Visit 6) (Day 90) .................................................................. 16 
8.1.7 
Unscheduled Visits ........................................................................................................ 16 
8.2 
Efficacy Assessments ....................................................................................................................... 17 
8.2.1 
Reflective total nasal symptom score (rTNSS) .......................................................... 17 
8.2.2 
Nasal Obstruction and Septoplasty Effectiveness (NOSE) Survey ........................ 17 
8.2.3 
Sino-Nasal Outcome Test (SNOT-22) ........................................................................ 17 
8.2.4 
Mini Rhinoconjunctivits Quality of LIfe Questionnaire (MiniRQLQ) ........................ 18 

  
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8.2.5 
Visual analog scale – Nasal Symptoms...................................................................... 18 
8.2.6 
Clinical global Impression – Improvement (CGI-I) .................................................... 18 
8.3 
Safety and Other Assessments ....................................................................................................... 18 
8.3.1 
Physical Nasal exam ..................................................................................................... 18 
8.3.2 
Pain Numeric Rating Scale ........................................................................................... 19 
8.3.3 
Clinical Evaluation of Nasal Congestion and Turbinate Hypertrophy..................... 19 
8.4 
Adverse Events, Adverse Device effects, Serious Adverse Events and unexpected adverse 
device effects ......................................................................................................................................................... 20 
8.4.1 
Definition of Adverse Events (AE) ............................................................................... 20 
8.4.2 
Definition of Adverse Device effect (AdE) .................................................................. 20 
8.4.3 
Definition of Serious Adverse Events (SAE) .............................................................. 20 
8.4.4 
Definition of unexpected Adverse Device effect (uade) ........................................... 20 
8.4.5 
Classification of an Adverse Event .............................................................................. 20 
8.4.6 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 21 
8.4.7 
Adverse Event Reporting .............................................................................................. 22 
8.4.8 
Serious Adverse Event Reporting ............................................................................... 22 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 22 
9.1 
Statistical Hypotheses ....................................................................................................................... 22 
9.2 
Sample Size Determination .............................................................................................................. 23 
9.3 
Populations for Analyses .................................................................................................................. 23 
9.4 
Statistical Analyses............................................................................................................................ 23 
9.4.1 
General Approach .......................................................................................................... 23 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 24 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 24 
9.4.4 
Safety Analyses .............................................................................................................. 24 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 25 
9.4.6 
Tabulation of Individual participant Data .................................................................... 25 
9.4.7 
Exploratory Analyses ..................................................................................................... 25 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 25 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 25 
10.1.1 
Informed Consent Process ........................................................................................... 25 
10.1.2 
Study Discontinuation and Closure ............................................................................. 25 
10.1.3 
Confidentiality and Privacy ........................................................................................... 26 
10.1.4 
Clinical Monitoring .......................................................................................................... 26 
10.1.5 
Quality Assurance and Quality Control ....................................................................... 27 
10.1.6 
Data Handling and Record Keeping ............................................................................ 27 
10.1.7 
Protocol Deviations ........................................................................................................ 28 
10.1.8 
Financial Disclosure ....................................................................................................... 28 
10.2 
Abbreviations ...................................................................................................................................... 29 
11 
REFERENCES ............................................................................................................................................. 30 
12 
APPENDIX I .................................................................................................................................................... 0 
 

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STATEMENT OF COMPLIANCE & INVESTIGATOR SIGNATURE PAGE 
 
I acknowledge that the trial will be carried out in accordance with International Conference on 
Harmonisation Good Clinical Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, and 21 CFR Part 812)  
 
Additionally, as a study Investigator: 
 
1. I understand this protocol contains information that is confidential and proprietary 
to Sponsor. 
2. Any additional information added to this protocol is also confidential and 
proprietary to Sponsor and must be treated in the same manner as the contents of 
this protocol. 
3. I have read the entire protocol. 
4. I understand what the protocol asks me to do as an Investigator. 
5. I will conduct this study following this protocol and will make a reasonable effort to 
complete the study in the time noted. 
6. I will provide this protocol to study staff under my supervision. My study staff will 
keep the protocol and associated documents confidential.  
7. I will discuss this information with the study staff to ensure they are fully informed 
about the study and the ClariFix device.  
8. I will not start enrolling in this study until it is approved by a governing Institutional 
Review Board.  
9. I understand the study may be terminated or enrollment suspended at any time by 
Sponsor, with or without cause, or by me if it becomes necessary to protect the 
interests of the study subjects. 
 
___________________________________________ 
Name of Investigator 
___________________________________________ 
____________________________ 
Investigator Signature 
Date (DD/MMM/YYYY) 

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1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Feasibility Study of Multi-Treatment Posterior Nasal Nerve Modulation for 
Treatment of Chronic Rhinitis 
 
Study Description: 
Prospective, non-randomized, feasibility study of adult patients for 
treatment to the posterior nasal nerve using cryotherapy at multiple 
treatment sites within the nasal cavity. 
 
Objectives: 
 
Evaluate the feasibility of treatment to the posterior nasal nerve at both 
the middle and inferior meatus locations within the nasal cavity. 
 
 
Primary Objective:  Evaluate the safety of treatment to the inferior meatus 
location 
 
 
Secondary Objectives:  Evaluate the effectiveness and tolerability of 
treatment at the inferior meatus location 
 
Endpoints: 
Primary Endpoint: Incidence of procedure related Serious Adverse Events 
(SAEs) and/or Serious Adverse Device Effects (SADE) 
 
Secondary Endpoints:  
• Incidence of procedure-related Adverse Events (AEs) or Adverse Device 
Effects (ADEs). 
• Tolerability of treatment via verbal report of pain/discomfort. 
• Nasal symptoms using rTNSS scale at 30- and 90-Days post-treatment. 
• Nasal congestion and turbinate hypertrophy as assessed by physician at 
30- and 90-Days post-treatment. 
 
Exploratory Endpoints:  
• Physician Evaluation of ease of treatment delivery using study device 
for inferior meatus location. 
 
Study Population: 
Up to 30 adult subjects diagnosed by ENT Physician with chronic rhinitis 
will be enrolled and treated in-office. 
 
Clinical Site(s) 
Up to 5 U.S. sites 
 
Study Device: 
Arrinex ClariFix™ Cryotherapy Device 
 
Study Duration: 
9 Months 
 
Participant Duration: 
Approximately 3.5 months 
 
 

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1.2 
SCHEMA 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Study Activity 
Screening (V1) 
Day -30 to 0 
Baseline (V2) 
Day -7 to 0 
Treatment (V3) 
Day 0 
1-Week Follow-up (V4) 
Day 7 (±3 days) 
1-Month Follow-up (V5) 
Day 30 (±7 days) 
3-Month Follow-up (V6) 
Day 90 (±14 days) 
Unscheduledb 
Informed Consent 
X 
 
 
 
 
 
 
Demographics Questionnaire 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Concomitant Medication 
X 
X                                                                X 
X 
Physical/Endoscopic Nasal Exam 
X 
 
 
Xc 
X 
X 
X 
Reflective Total Nasal Symptom Score (rTNSS) 
X 
X 
 
 
X 
X 
X 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
 
Nasal Obstruction Symptom Evaluation (NOSE) 
Instrument 
 
X 
 
 
X 
X 
 
Sino-Nasal Outcome Test (SNOT-22) 
 
X 
 
 
X 
X 
 
Visual Analog Scales – Nasal Symptoms 
 
X 
 
 
X 
X 
 
Mini Rhinoconjunctivitis Quality of Life 
Questionnaire (MiniRQLQ) 
 
X 
 
 
X 
X 
 
Clinical Global Impression – Improvement (CGI-I) 
 
 
 
 
X 
X 
 
Treatment with ClariFix 
 
 
X 
 
 
 
 
Pain Numeric Rating Scale 
 
 
X 
 
 
 
 
Adverse Event review and evaluationa 
 
 
X                                                 X 
X 
Study Exit 
 
 
 
 
 
X 
 
a. AEs to be collected beginning at treatment timepoint.  Any AEs experienced between Consent to Treatment 
timepoints should be evaluated for continued eligibility and suitability for study participation and may be 
documented as medical history, if applicable. 
b. Unscheduled Visit activities to be completed based on reason for Visit and discretion of the Investigator. 
c. Physical/Endoscopic Nasal Exam may be performed at the discretion of the Investigator in the event of a new or 
continuing AE. 
 
 
 
 

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2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Anatomic dissections have demonstrated that parasympathetic nerve fibers innervate the nasal cavity 
within the inferior meatus as well as the middle meatus.  In studies to date (see Section 2.3), 
interruption of these nerve signals in the middle meatus has demonstrated a response rate of ~80% with 
reduction in rhinorrhea and congestion symptoms by approximately 50%.  Extending this interruption of 
the nasal nerve fibers in the inferior meatus may improve the symptom reduction and/or response rate 
in patients with chronic rhinitis.    
 
2.2 
BACKGROUND  
Rhinitis is a very common condition throughout the world. In the Unites States alone, it affects 10-30% 
of the adult general population.  This accounts for 30-60 million people in the United States and the 
prevalence has been increasing in recent decades, making it the fifth most common chronic disease in 
the US.  Rhinitis is the inflammation of the nasal mucosa affecting patients with distressing symptoms of 
at least one of the following symptoms:  nasal congestion, rhinorrhea, sneezing, and nasal itching.   
 
The current standard of care to control this disease starts with pharmacologic interventions, typically 
beginning with over the counter medications.  Nasal steroids (i.e. Flonase, Nasonex) and oral anti-
histamines (i.e. Claritin, Allegra, Zyrtec) are the mainstays of medical management.  They have their 
challenges, however, as they require daily use and have limited effectiveness, especially against non-
allergic rhinitis. Sedating anti-histamines such as Benadryl are used intermittently but the somnolent 
side effects are not usually well tolerated.   
 
Prescription medications are used when OTC medication management fails.  Oral steroids can be 
effective in the short term but carry more severe long-term side effects including immunosuppression, 
osteoporosis, Cushing syndrome and diabetes.  Adrenergic agents such as Afrin are effective but quickly 
result in tolerance and “rebound” (recurrence and sometimes worsening of symptoms when off the 
medication). 
 
When pharmacological treatments do not provide adequate response, surgical techniques have also 
been developed to treat rhinitis. These techniques include electrocautery, chemocautery, laser cautery, 
microdebrider turbinoplasty, radiofrequency ablation, subtotal turbinectomy, total inferior 
turbinectomy, and submucosal resection. These primarily seek to address the nasal obstructive 
component through reduction of the inferior turbinate.  
 
Use of various cryosurgical tools for destruction of tissue in the nasal passageway to treat nasal 
obstruction or symptoms of rhinitis has been reported in the literature.1,2,3,4,5,6,7,8,9,10,11  Target tissue in 
the nasal passageway that was subjected to cryosurgery included the nasal soft tissue covering the 
turbinates, which included nasal nerves. All studies included patient-reported outcomes of nasal 
symptoms, which is a commonly accepted method for demonstrating the effectiveness outcomes in the 
nasal passageway. Physicians also performed visual assessments of nasal congestion and recorded the 
presence of complications including resolution of any adverse symptoms. Although these published 
reports reflect improvement in symptoms and a low rate of complications, endoscopic cryotherapy 
techniques and tools have not been fully optimized to achieve consistent outcomes.  
 

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The ClariFix Cryoablation clinical study evaluated cryosurgical tools12.  In this study, the safety and 
effectiveness of cryosurgical posterior nasal tissue ablation for the treatment of rhinitis using the ClariFix 
Device was assessed.  The initial clinical findings demonstrated a significant reduction in rhinorrhea and 
nasal congestion with minimal to no adverse events (see section 2.3).  In this study, the cryotherapy was 
applied to unwanted tissue including postganglionic branches of the vidian nerve (referred to as 
Posterior Nasal Nerves PNN) along the lateral wall in the posterior region of the middle meatus just 
inferior to the sphenopalatine foreman (SPF).   
 
Upon further investigation, Dr. Benjamin Bleier et al. noted that additional postganglionic fibers may 
project from the pterygopalatine ganglion via multiple individual postganglionic rami to supply the nasal 
mucosa13. Anatomic dissections showed that accessory posterolateral nerves were noted in 87.5% of 
specimens (14 of 16).  Of the 25 additional posterolateral nerves identified, the most common location 
(40%, 10/25) was within 1 cm posterosuperior to the horizontal attachment of the inferior turbinate; 
however, 28% (7/25) were noted within 5 mm anteroinferior to this attachment (see Figure 1).  The 
initial clinical studies demonstrated that the posterosuperior location had a clinical effect in roughly 80% 
of patients, so the intent of this study is to evaluate the safety and effectiveness of Cryoablation along 
the lateral wall in the middle meatus (as done in previous studies) as well as the inferior meatus in 
patients that suffer from Chronic Rhinitis.    
 
 
Figure 1.  Illustration of medical aspect of the left palatine bone indicating the location of all 25 
accessory posterolateral nerves identified.  The closed dots represent nerves traversing directly 
through the bone whereas the open circles represent nerves that were associated with distinct 
foramina. 
 
2.3 
REPORT OF PRIOR INVESTIGATIONS 
CT-0001 ClariFix Cryoablation Study 
A pilot clinical study was performed to evaluate the performance of the ClariFix device as a cryosurgical 
tool to treat subjects with chronic rhinitis. This study was a prospective, multi-center, single-arm 
interventional study of the ClariFix device. The study protocol was reviewed and approved as non-
significant risk (NSR) by Quorum Review IRB. Three investigational sites were selected in the United 

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States. All treatments were performed on consented awake subjects in an office setting by experienced 
otolaryngologists. Subjects were seen in the office at 7, 30, and 90 days post-treatment for follow-up 
assessments. Extended follow-up to a maximum of one-year post-treatment was conducted to assess 
the durability of treatment outcomes.  The primary safety endpoint for the study was the frequency of 
serious device or procedure-related adverse events (SAEs). The primary efficacy endpoint was the 
change in subject reported nasal symptoms at the follow-up intervals relative to baseline. Nasal 
symptoms were assessed using the reflective Total Nasal Symptom Scale (rTNSS) and a Visual Analog 
Scale (VAS). 
 
A total of twenty-seven (27) subjects were enrolled and received bilateral treatments.  Twenty-seven 
(27) subjects completed 1-month follow-up and twenty-four (24) subjects completed 90-day follow up (3 
subjects were lost-to-follow-up).  Twenty-four (24) subjects participated in extended follow-up. 
Treatments were successfully completed bilaterally with no complications in 100% of subjects (n=27) 
using injected or topical anesthesia in the office. Nasal symptoms assessed by rTNSS were reduced 
significantly at each follow-up interval compared to baseline. The average rTNSS score was reduced by 
58% from 6.2 at baseline to 2.6 at 30 days and maintained at 2.7 at 90 days (56% reduction). Extended 
follow-up data showed sustained improvements, with an average rTNSS of 2.3 at 180 days post-
treatment. Eighty-one percent (22/27) of subjects had improved rTNSS scores at 30 days and 79% 
(19/24) of subjects had improved rTNSS scores at 90 days. The VAS symptom data similarly 
demonstrated significant reductions in nasal symptoms. The average total VAS score was reduced by 
50% and 53% at 30 and 90 days, respectively. There was no device or procedure-related serious adverse 
events or unanticipated adverse device effects reported during the course of the study. 
 
CT-0003 ClariFix Cryotherapy Device in Subjects with Chronic Rhinitis “FROST” Study 
A post-market clinical study was initiated to evaluate the safety and efficacy of the ClariFix device in 
subjects with chronic rhinitis.  The “FROST” study was a prospective, multi-center, single-arm 
interventional study.  The study protocol was deemed NSR by Quorum Review IRB (as central IRB) and 
by Advarra IRB (formerly Chesapeake IRB) for an individual site. Seven (7) investigational sites were 
selected and initiated, with six of the seven enrolling subjects. Subjects that were consented and met 
eligibility criteria received treatment in an office setting by Otoloaryngologist.  All subjects were 
followed-up with via phone at 1-day post, and were seen in-office at 7-, 30-, 90-, 180-, 270- and 365-
days post-treatment.  Subjects that had an improvement in their overall rTNSS score at both the 270- 
and 365-day post-treatment were offered participation in an extended follow-up that includes office 
visits at 15-, 18-, 21-, and 24-months post-treatment.  The rTNSS scale was administered at all in-office 
study visits and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was administered at 90-
days and 18- and 24-months post-treatment. 
 
A total of one hundred (100) subjects were enrolled and received bilateral treatment with the ClariFix 
device at the middle meatus location within the nasal cavity.  At this time, all 100 subjects completed 
the 30-day follow-up, ninety-eight (98) have completed through 90-day follow-up with two (2) subjects 
having exited the study at that timepoint, and data analysis has been completed through this timepoint.  
The study is still currently in follow-up with visits completed as follows:  180-day n=89, 270-day n=77, 
365-day n=56, 15-month n=12, and 18-month n=1.  As of the 90-day timepoint, the average per subject 
rTNSS score was reduced by 48.4% from 6.15 at baseline to 3.06 at 30-days and to 3.02 at 90 days 
(46.5% reduction), with the largest improvements in the individual symptom scores for rhinorrhea 
(change from baseline of 2.42 to 1.05 at 90-days) and congestion (change from baseline of 2.07 to 1.05 
at 90-days). The RQLQ data at 90-days showed a 45.8% reduction from an overall score of 3.12 at 
baseline to 1.63 at 90-days. A total of 29 adverse events were reported at the 90-day timepoint, with 

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one (1) probable adverse device effect and procedure-related, two (2) procedure related adverse 
events, and two (2) serious adverse events (one not related, and one possible device related). 
 
Summary 
In both the 27 subject pilot study and 100 subject FROST study, office-based treatment using the ClariFix 
device was demonstrated to be safe, well-tolerated, and effective in reducing nasal symptoms in 
subjects with chronic rhinitis. This study will build on those results and is designed to assess the safety 
and effectiveness of the ClariFix device when used to ablate unwanted tissue in the nasal passageway of 
subjects with chronic rhinitis. 
 
2.4 
DEVICE DESCRIPTION 
The ClariFix™ device (K162608) is an FDA 510(k) cleared Class II cryosurgical tool indicated for the 
destruction of unwanted tissue during surgical procedures, including in adults with chronic rhinitis.   
 
The ClariFix device (Figure 2) is a handheld cryosurgical device which provides focal, controlled freezing 
to the target tissue.  In order to deliver treatment, a nitrous oxide canister is inserted into the device.  
The device’s cryoprobe is placed in contact with the target tissue, under direct visualization.  The low 
profile semi-flexible cannula allows the user to maintain visibility of the cryoprobe and apply pressure to 
target tissue with the cryoprobe to ensure contact throughout the treatment.  Once the cryoprobe is in 
the desired position, the physician manually initiates the flow of cryogen and ablates unwanted tissue.  
The nitrous oxide gas is contained within the cryoprobe and allowed to exit the device at the handle 
away from the subjects.   
 
The ClariFix device consists of a Cryoprobe, Cannula, On/Off valve, Handle, & Cap.  The device is 
provided sterile and designed for single patient use. 
 
The device is provided with 10-ml cryogen canisters.  The cryogen canisters are provided separately.  
The canisters are provided non-sterile and each canister contains enough cryogen for approximately 60 
seconds (10-ml) of ablation time.  
 
 
Figure 2.  ClariFix™ Device 
 
 
 

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2.5 
RISK/BENEFIT ASSESSMENT   
 
2.5.1 KNOWN POTENTIAL RISKS  
The study cryotherapy procedure involves transnasal placement of the ClariFix device under endoscopic 
visualization and use of local anesthesia. In order to minimize risks associated with the study, the 
procedure will be performed by practicing otolaryngologists experienced in transnasal procedures. 
Further, subjects with known allergies to local anesthetic agents shall be excluded from participation in 
the study. 
 
While nasal endoscopy is generally known to be safe, anticipated risks may include, but are not limited 
to: 
• 
Temporary pain, discomfort or irritation 
• 
Bleeding 
• 
Cerebrospinal fluid (CSF) leak 
 
Similarly, while generally known to be safe, submucosal placement of a needle and delivery of local 
anesthesia may be additionally associated with the following risks, not limited to: 
• 
Minor bleeding 
• 
Pain with injection 
• 
Facial numbness or tingling 
• 
Sedation 
• 
Tachycardia, nervousness, anxiety 
• 
Lightheadedness, dizziness, confusion,  
• 
Muscular twitching, tremors 
• 
Infection 
• 
Allergic reaction  
• 
Lidocaine or Tetracaine toxicity with overdose 
• 
Visual disturbance 
• 
Vomiting 
• 
Headache 
• 
Tinnitus 
• 
Seizures 
• 
Hypotension, bradycardia 
• 
Unconsciousness 
• 
Respiratory arrest 
• 
Cardiac arrest 
 
While generally considered safe, cryotherapy has known potential risks14 including, but not limited to: 
• 
Postoperative bleeding 
• 
Epistaxis 
• 
Nasal obstruction 
• 
Nasal crusting 
• 
Ear blockage 
 

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In addition, the specific nature of cryosurgery using the ClariFix Device results in a known potential for 
adverse events related to the cold application.  Potential risks and complications are outlined in the IFU 
(See Appendix I).  
 
2.5.2 KNOWN POTENTIAL BENEFITS  
Use of the ClariFix device as a tool during cryosurgery may reduce the symptoms of chronic rhinitis.  
Improvement in rhinitis symptoms may improve patients’ quality of life and may improve work or school 
productivity.   
 
This study may provide valuable information as to the underlying mechanisms of rhinitis, which may 
enable the development of more effective devices in the future. 
 
2.5.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
Potential risks are typically transient and resolve, however potential improvement in quality of life and 
symptoms associated with rhinitis have been shown to be durable through at least one-year post-
treatment. 
 
3 
OBJECTIVES AND ENDPOINTS 
The study overall objective is to evaluate the feasibility of treatment to the posterior nasal nerve at both 
the middle and inferior meatus locations within the nasal cavity for improvement in the symptoms of 
chronic rhinitis. 
 
OBJECTIVES 
ENDPOINTS 
Primary 
 
Evaluate the safety of treatment to the inferior 
meatus location 
Incidence of procedure related Serious Adverse 
Events (SAEs) and/or Serious Adverse Device 
Effects (SADE) 
Secondary 
 
Evaluate the effectiveness and tolerability of 
treatment at the inferior meatus location  
1. Incidence of procedure-related Adverse 
Events (AEs) or Adverse Device Effects (ADEs). 
2. Tolerability of treatment via verbal report of 
pain/discomfort. 
3. Nasal symptoms using rTNSS scale at 30- and 
90-Days post-treatment. 
Tertiary/Exploratory  
 
Physician Evaluation of ease of treatment delivery 
using study device for inferior meatus location. 
Physician-reported ease-of-use rating. 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
Prospective, non-randomized, open-label, multi-center, interventional feasibility study. 
 
 
 

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4.2 
END OF STUDY DEFINITION 
A subject is considered to have completed the study if he or she has completed all phases of the study 
including the last visit shown in the Schedule of Activities (SoA), Section 1.3. 
 
The end of the study is defined as completion of the last visit shown in the SoA in the trial for all 
subjects. 
 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Subject is ≥18 years of age.  
2. Subject has had presence of moderate to severe rhinorrhea symptoms and mild to severe nasal 
congestion symptoms for >3 months.  
3. At the Baseline Visit, subject has, as determined by rTNSS, moderate to severe symptoms of 
rhinorrhea (individual symptom score of >1), mild to severe symptoms of nasal congestion 
(individual symptom score >0). 
4. Subject has had documented allergy test within the last 10 years that defines whether or not 
subject has allergies to perennial and seasonal allergens, or is willing to have one performed 
prior to study exit. 
5. Subject is able to provide informed consent and willing to complete study activities and visits 
per protocol. 
 
5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Subject has clinically significant anatomic obstructions that limit access to the posterior nose 
including severe septal deviation, nasal polyps, and sinonasal tumor. 
2. Subject has had prior sinus or nasal surgery that significantly alters the anatomy of the posterior 
nose. 
3. Subject has moderate to severe ocular symptoms as determined.  
4. Subject has a history of epistaxis in the past 3 months. 
5. Subject has a history of rhinitis medicamentosa. 
6. Subject has had prior head or neck irradiation. 
7. Subject has active or chronic nasal or sinus infection. 
8. Subject is pregnant. 
9. Subject has an allergy or intolerance to anesthetic agent. 
10. Subjects with cryoglobulinemia, paroxysmal cold hemoglobinuria, cold urticaria, Raynaud’s 
disease, and/or, open and/or infected wounds at or near the target tissue.  
11. Subject is currently participating in another clinical research study. 
12. Subject has any physical condition that, in the investigator’s opinion, would prevent adequate 
study participation or pose increased risk. 
 
 
 

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5.3 
SCREEN FAILURES 
Screen failures are defined as subjects who consent to participate in the clinical trial but are not 
subsequently enrolled in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants. Minimal information includes demography, screen 
failure details, and eligibility criteria. 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) may not be 
rescreened.  
 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
It is anticipated that up to 5 U.S. based sites will participate in this study.  A sufficient number of 
potential subjects will be screened to be able to complete targeted enrollment of up to thirty (30) 
subjects within three (3) months of study initiation.   
 
Targeted study population will be pre-screened based on eligibility criteria and recruited from patients 
within the practice of otolaryngology practices.  Additionally, subjects may be recruited into the practice 
by means of IRB approved recruitment materials, that may include, but are not limited to, web postings, 
posters, and mailers.  
 
While there is no known risk to pregnant or lactating females, as there is no need to evaluate the safety 
and efficacy of the study device in this population, they will be excluded from study participation.  
 
Participants will receive a stipend in the form of a pre-paid gift card for their participation in the study.  
The gift cards will be provided after the completion of each study visit’s activities. A schedule of stipends 
to be paid for each visit will be outlined in each site’s IRB-approved Informed Consent Form (ICF) 
document.  
 
6 
STUDY TREATMENT 
 
6.1 
STUDY TREATMENT ADMINISTRATION 
All subjects will receive bilateral cryoablation treatment with the ClariFix device per Instructions for Use 
(IFU) (See Appendix I).   
 
Each side of the nasal cavity will be treated in two locations (see Figure 3): (a) middle meatus and (b) 
inferior meatus.  Each location will receive approximately thirty (30) seconds of cryoablation treatment. 
 
 

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Figure 3: Cryoablation Treatment Locations. 
 
6.2 
DEVICE ACQUISITION AND ACCOUNTABILITY 
Sponsor will provide the ClariFix devices, at no cost, to be used for the subjects’ cryoablation 
treatments.   
 
Devices will be shipped and designated as study-use only.  Device usage will be tracked in site’s 
Regulatory documents and individual device lot numbers will be noted in Source documents and eCRFs.  
However, as the devices being use are FDA cleared and being used on-label, if necessary, devices may be 
pulled from site’s commercial inventory. 
 
6.3 
CONCOMITANT MEDICATIONS 
For this protocol, a prescription medication is defined as a medication that can be prescribed only by a 
properly authorized/licensed clinician. Medications to be reported in the Case Report Form (CRF) are 
concomitant prescription medications, over-the-counter medications and supplements. 
 
Medication usage will be documented for medications subject is currently taking at time of Screening 
Visit, for any medication usage stopped within the previous thirty (30) days, and for medication changes 
(started, stopped, or change of dose/frequency) through study exit.  Medications usage, both 
prescription and over-the-counter, for the following indications and/or systems will be documented in 
the Concomitant Medication Log for each subject: 
 
• 
Allergies 
• 
Nasal, Ear and Throat 
• 
Asthma 
• 
Migraines 
• 
Blood thinners/anti-coagulants 
 

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Medications taken in conjunction with time of treatment or post-treatment for pain or anxiety, both 
prescription and over-the-counter, pain or discomfort will be documented. 
 
Additionally, any medication that is determined by the Investigator to be a potential safety issue or 
concern, and/or any medication taken in connection with treatment for an Adverse Event will be 
documented. 
 
Subjects will refrain from the use of ipratropium bromide (i.e. Atrovent) at least 3 days prior to 
treatment and through the 3-Month timepoint. 
 
At the Investigator’s discretion, subjects that have an active coagulation disorder or are receiving anti-
coagulants, may be asked to temporarily stop usage prior to treatment.  
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Significant study non-compliance  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the Study 
Exit Case Report Form (CRF). Subjects who sign the informed consent form but do not receive the study 
treatment may be replaced.  Subjects who sign the informed consent form and receive the study 
treatment, and subsequently withdraw, or are withdrawn or discontinued from the study, may be 
replaced at the discretion of the Sponsor. 
 
7.2 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for 2 or more scheduled visits 
and is unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit and counsel the 
participant on the importance of maintaining the assigned visit schedule and ascertain if the 
participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the participant’s medical record or study file.  

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• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
STUDY PROCEDURES 
 
8.1.1 SCREENING VISIT (VISIT 1) (DAY -30 TO 0) 
Potential study subjects will be pre-screened against study eligibility criteria.  Those individuals, that 
meet pre-screening criteria will be offered participation in the study and will be consented (see Section 
10.1.1). 
 
The Screening Visit may occur in-office up to 30 days prior to the Treatment Visit (Visit 1).  Visit 1 may 
occur on the same day as the Baseline (Visit 2) and Treatment (Visit 3) Visits. 
 
After obtaining informed consent, the following study activities will be completed: 
 
1. Subject to complete Subject Demographics Questionnaire (See Addendum: Patient 
Questionnaires).  Data collected includes month and year of birth, biological gender, ethnicity 
and race. 
2. Subject will complete rTNSS questionnaire (see Section 8.2.1). 
3. Concomitant Medications will be documented (see Section 6.3). 
4. Relevant Medical History will be documented.  This will include, but not limited to, the 
following: 
a. History of nasal symptoms including rhinitis, epistaxis and sinusitis; 
b. History of facial pain, TMJ, ocular symptoms, and ear/nose complaints; 
c. Prior allergy testing; and 
d. History of rhinitis medication usage and response to treatment. 
5. Physician will complete a Physical Nasal Exam (see Section 8.3.1) and document findings. 
6. Investigator will review Inclusion/Exclusion criteria, and subjects meeting criteria will be 
scheduled for the Baseline Visit (Visit 2). 
 
Note:  Due to post-market, on-label use of device, pregnancy exclusion will be based upon self-report.  
Pregnancy testing will not be required to confirm eligibility. 
 
8.1.2 BASELINE VISIT (VISIT 2) (DAY -7 TO 0) 
Subjects meeting eligibility criteria will return in-office for the Baseline Visit (Visit 2).  The Baseline Visit 
may be completed the same calendar day as the Screening (Visit 1) and Treatment (Visit 3) Visits, 
however it must be completed no earlier than seven (7) calendar days prior to the Visit V3.  
 
At Visit 2, the following study activities will be completed: 
 
1. Subject will complete rTNSS questionnaire.   
Note:  If Visit 2 is completed the same calendar day as Visit 1, second rTNSS is not to be 
completed.   
2. Concomitant Medication usage will be updated. 

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3. Eligibility Criteria will be confirmed.   
a. Subjects meeting criteria will be considered enrolled and continue Visit 2 activities. 
b. Subjects not meeting criteria will be considered a Screen Failure and their study 
participation will be complete. 
4. Subject will complete the NOSE (see Section 8.2.2), SNOT-22 (see Section 8.2.3), VAS for Nasal 
Symptoms (see Section 8.2.5), and MiniRQLQ (see Section 8.2.4). 
 
Treatment Visit, if on another day, should be confirmed with the Subject.  
 
Additionally, for subjects that do not have confirmation of a prior allergy test within the last 10 years, 
they will be scheduled for allergy testing prior to study exit. 
 
8.1.3 TREATMENT VISIT (VISIT 3) (DAY 0) 
Enrolled subjects will receive bilateral cryoablation treatment in-office.  The Treatment Visit (Visit 3) 
may occur on the same calendar day as Visits 1 and 2 and must be completed within thirty (30) days 
from Visit 1 and no later than seven (7) calendar days of Visit 2. 
 
Subjects will be begin being assessed for Adverse Events (AEs) starting at Visit 3, with any AEs occurring 
at Visit 3 or after through study completion (see Section 8.4). 
 
At Visit 3, the following study activities will be completed: 
 
1. Concomitant Medication usage will be updated. 
2. Physician will perform bilateral cryoablation treatment with the ClariFix device, per IFU.  See 
Section 6. 
a. Subject will be asked for a Verbal Pain Numeric Rating Scale (NRS) immediately after 
cryoablation treatment at each individual treatment location (see Section 8.3.2) and 
documented. 
3. Subject will be monitored and assessed for Adverse Events. 
a. Should post-procedure discomfort or pain be experienced, in addition to an adverse 
event form, subject will be asked for a Verbal Pain NRS.  
4. Subject will be scheduled for 1-Week Follow-up (Visit 4). 
 
8.1.4 7-DAY FOLLOW-UP VISIT (VISIT 4) (DAY 7) 
Subjects will return to the office at one (1) week (±3 days) from Visit 3 for the 1-Week Follow-up Visit 
(Visit 4).  
 
At Visit 4, the following study activities will be completed: 
 
1. Concomitant Medication usage will be updated. 
2. Subject will be assessed for any new Adverse Events experienced since Visit 3 and/or review of 
previously unresolved Adverse Events. 
3. If a continuing or new study-related AE, Physician may choose to complete a Physical Nasal 
Exam (see Section 8.3.1) and document findings. 
4. Subject will be scheduled for 1-Month Follow-up visit (Visit 5). 
 
 
 

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8.1.5 1-MONTH FOLLOW-UP VISIT (VISIT 5) (DAY 30) 
Subjects will return to the office at thirty (30) days (±7 days) from Visit 3 for the 1-Month Follow-up Visit 
(Visit 5).  
 
At Visit 5, the following study activities will be completed: 
 
1. Subject will complete rTNSS, NOSE, SNOT-22, VAS for Nasal Symptoms and MiniRQLQ 
questionnaires. 
2. Concomitant Medication usage will be updated. 
3. Subject will be assessed for any new Adverse Events experienced since Visit 4 and/or review of 
previously unresolved Adverse Events. 
4. Physician will complete Physical Nasal Exam and document findings. 
5. Investigator will complete Clinical Global Impression—Improvement (CGI-I) scale (see Section 
8.2.5). 
6. Subject will be schedule for 3-Month Follow-up visit (Visit 6). 
 
8.1.6 3-MONTH FOLLOW-UP VISIT (VISIT 6) (DAY 90) 
Subjects will return to the office at ninety (90) days (±14 days) from Visit 3 for the 3-Month Follow-up 
Visit (Visit 6).  
 
At Visit 6, the following study activities will be completed: 
 
1. Subject will complete rTNSS, NOSE, SNOT-22, VAS for Nasal Symptoms and MiniRQLQ 
questionnaires. 
2. Concomitant Medication usage will be updated. 
3. Subject will be assessed for any new Adverse Events experienced since Visit 5 and/or review of 
previously unresolved Adverse Events. 
4. Physician will complete Physical Nasal Exam and document findings. 
5. Investigator will complete Clinical Global Impression—Improvement scale (see Section 8.2.5). 
6. Investigator will complete the Study Exit form. 
 
Subject participation will be complete at the Visit 6 time point. 
 
8.1.7 UNSCHEDULED VISITS 
An Unscheduled Visit (UV) may occur after Visit 3 through the end of the study participation.  A UV may 
occur due to a study-related adverse event.   
 
The following activities will be completed as part of a UV: 
 
• 
Concomitant Medication usage will be updated. 
• 
Subject will be assessed for any new Adverse Events experienced since previous Visit and/or 
review of previously unresolved Adverse Events. 
 
Additional data may be collected and documented at the discretion of the Investigator.  Activities that 
may be completed at the Investigator’s discretion is as follows: 
 
• 
Physical Nasal Exam 

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• 
Physician completed CGI-I 
 
8.2 
EFFICACY ASSESSMENTS  
 
8.2.1 REFLECTIVE TOTAL NASAL SYMPTOM SCORE (RTNSS) 
The primary effectiveness endpoint will be assessed based on the four-symptom reflective Total Nasal 
Symptom Score (rTNSS)15,16 (See Addendum: Patient Questionnaires). rTNSS is a validated symptom 
severity scoring system that consists of the sum of four (4) individual subject-assessed symptom scores 
for rhinorrhea, nasal congestion, nasal itching, and sneezing. Each item is scored on a scale of 0 (No 
Symptoms) to 3 (Severe Symptoms) and is based on the subject’s evaluation of symptom severity over 
the preceding two (2) weeks at study visits.  The four-symptom rTNSS has a possible score of 0-12. The 
reflective scores will be based on the subject’s evaluation of symptom severity over the preceding two 
(2) week period. 
 
In this study, a modified version of the rTNSS will be utilized that adds two additional questions for 
rating of post-nasal drip and clearing of throat.  However, these will not be included in the analysis of 
the 4-item rTNSS and will be analyzed separately.  
 
Subjects will be asked to assess their symptoms at the Screening Visit (Visit 1), Baseline Visit (Visit 2) (if 
on a day other than Screening), and at the 1-Month (Visit 5) and 3-Month Follow-up (Visit 6) Visits. The 
subjects will be asked to assess each symptom individually (runny nose, congestion, nasal itching, 
sneezing) (See Addendum: Patient Questionnaires). Subject may be reminded of baseline score prior to 
treatment, as appropriate. 
 
8.2.2 NASAL OBSTRUCTION AND SEPTOPLASTY EFFECTIVENESS (NOSE) SURVEY 
The Nasal Obstruction and Septoplasty Effectiveness (NOSE) survey17 consists of 5 items, each scored 
using a 5-point Likert scale to make a total score rant of 0 to 100.  The subject completes the survey by 
circling the response closest to describing their current symptoms over the past 1 month (See 
Addendum: Patient Questionnaires).  The sum of those response is multiplied by a factor of 5 to base 
the scale out of a possible score of 100 for analysis. Higher scores indicate worse obstruction.   
 
The NOSE survey will be administered at the Baseline (Visit 2), and 1- (Visit 5) and 3-Month (Visit 6) 
Follow-up Visits. 
 
8.2.3 SINO-NASAL OUTCOME TEST (SNOT-22) 
The Sino-Nasal Outcome Test (SNOT-22)18 is a validated patient-reported questionnaire to assess the 
impact of nasal symptoms on a patient’s quality of life.   The questionnaire consists of 22 categories, 
each scored using a 5-point Likert scale (0 = No Problem to 5 = Problem as base as it can be).  The 
subject completes the survey by circling the response closest to describing “how bad” their current 
symptoms are in each category over the past two (2) weeks, and then checks up to five (5) categories 
that are the “Most Important Items” affecting their health (See Addendum: Patient Questionnaires).  
The sum of the responses produces a total possible score of 0 to 110 for analysis.  Higher scores indicate 
worse obstruction.   
 
The SNOT-22 questionnaire will be administered at the Baseline (Visit 2), and 1- (Visit 5) and 3-Month 
(Visit 6) Follow-up Visits. 
 

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8.2.4 MINI RHINOCONJUNCTIVITS QUALITY OF LIFE QUESTIONNAIRE (MINIRQLQ) 
The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ)19 is a validated tool that measures 
the functional (physical, emotional, and social) problems associated with rhinitis (See Addendum: 
Patient Questionnaires).  The MiniRQLQ was adapted from the original 28-item Rhinoconjunctivitis 
Quality of Life Questionnaire (RQLQ)20, which included 28-items in 7 domains (sleep, non-
Rhinoconjunctivitis symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, 
and emotional function).  The MiniRQLQ, is a 14-item questionnaire that covers 5 domains of activities, 
practical problems, nose symptoms, eye symptoms, and other symptoms. Subjects are asked to recall 
impairments experienced during the previous week and to respond to each item on a 7-point scale (0 = 
no impairment, 6 = maximum impairment). The overall RQLQ score is the mean of all 14 responses and 
the individual domain scores are the means of the items in those domains. 
 
The MiniRQLQ questionnaire will be administered at the Baseline (Visit 2), and 1- (Visit 5) and 3-Month 
(Visit 6) Follow-up Visits. 
 
8.2.5 VISUAL ANALOG SCALE – NASAL SYMPTOMS 
A Visual Analog Scale (VAS) is a measurement instrument that tries to measure a characteristic or 
attitude that is believed to range across a continuum of values and cannot easily be measured.  It is 
often used in epidemiologic and clinical research to measure the intensity or frequency of various 
symptoms.  From the subject’s perspective, this spectrum appears continuous and does not make 
discrete jumps, as a categorization of none, mild, moderate and sever would suggest.   
 
In this study, a 100mm scale (see Addendum: Patient Questionnaires) will be used to evaluate the 
individual symptoms over the last week of rhinitis (runny nose), nasal congestion (stuffiness), and overall 
nasal symptoms. Subjects will report record their symptoms, based on the last week, on a continuum of 
0mm on the left, representing no symptoms, to 100mm on the right, representing severe symptoms. 
 
The VAS for Nasal Symptoms will be administered at the Baseline (Visit 2), and 1- (Visit 5) and 3-Month 
(Visit 6) Follow-up Visits. 
 
8.2.6 CLINICAL GLOBAL IMPRESSION – IMPROVEMENT (CGI-I) 
The Clinical Global Impression--Improvement (CGI-I)21 rating scales is a clinician completed subject 
assessment of the changes of symptoms since time of treatment based on their clinical experience.  The 
CGI-I is a 7-point Likert scale that ranges from a scale of 1 being “Very Much Improved” to 7 being “Very 
Much Worse”.   
 
The CGI-I will be completed that the 1- (V5) and 3-Month (V6) Follow-up Visits at the completion of the 
Physical Nasal Exam (See Section 8.3.1).  Additionally, the CGI-I may, at the discretion of the clinician, be 
administered at an Unscheduled Visit (See Section 8.1.7). 
 
8.3 
SAFETY AND OTHER ASSESSMENTS 
 
8.3.1 PHYSICAL NASAL EXAM 
A physical nasal evaluation of the treatment area and nasal cavity will be performed by a licensed 
clinician via endoscope at the Screening (Visit 1), 1-Week (Visit 4 due to AE occurrence or monitoring), 1-
Month (Visit 5) and 3-Month (Visit 6).  
 

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IMPORTANT:  Except for 1-Week (Visit 4), if applicable, subjects are not to be decongested prior to the 
Physical Nasal Exam. 
 
Prior to decongestant, bilateral endoscopic videos or images are to be collected capturing the head of 
the inferior and middle turbinates (see Section 8.3.3). 
 
The clinician will assess each side of the nasal cavity for hypertrophy of the middle and inferior 
turbinates and congestion using a 0 to 3 scale (0=None, 1=Mild, 2=Moderate, or 3=Severe).  
 
After decongestant, a second bilateral endoscopic videos or images are to be collected capturing the 
head of the inferior and middle turbinates. 
 
At Visit 4 (if applicable), Visit 5 and Visit 6, the clinician will assess each treatment area (left middle 
meatus, left inferior meatus, right middle meatus and right inferior meatus) for bleeding, crusting, and 
swelling using the same scale of 0 to 3.   
 
An endoscopic exam may be completed at an Unscheduled Visit at the discretion of the Investigator, in 
the event of a study-related adverse event. 
 
8.3.2 PAIN NUMERIC RATING SCALE 
A pain numeric rating scale (NRS)22 for pain function best for the patient’s subjective feeling of the 
intensity of pain right now—present pain intensity.  The NRS utilizes an 11-point scale of zero to 10.  
Subjects verbally report pain on the scale of 0 to 10 with zero representing “no pain” and 10 
representing “worst pain imaginable”.  
 
Pain and/or discomfort during the Treatment Visit (Visit 3) will be collected for each individual freeze 
treatment location (left middle meatus, left inferior meatus, right middle meatus, and Right Inferior 
Meatus), and any post-treatment pain and/or discomfort reported immediately following the treatment. 
 
8.3.3 CLINICAL EVALUATION OF NASAL CONGESTION AND TURBINATE HYPERTROPHY 
Images, photographic and video, collected at the time of Physical Nasal Exam (See Section 8.3.1) may be 
evaluated for visible nasal congestion and turbinate hypertrophy by an independent physician reviewer.  
Images will be collected at the Screening (Visit 1), 1-Month (Visit 5) and 3-Month (Visit 6) Follow-up 
timepoints.  
 
Images will be of the internal nasal valve only.  In the event that only video is collected, still shots will be 
taken by sponsor showing the internal nasal valve only prior to images being available to physician 
reviewer.  Images to be reviewed are the heads of the inferior and middle turbinate for each side of the 
nose. 
 
Images will be stored on thumb drives at the individual site, and videos transferred to Sponsor by 
designated Sponsor representatives via a secure data transfer. Transferred files are not to contain 
patient health information (“PHI”) data (i.e., name, date of birth, etc.).  Files will be identified by the 
subject’s study identification number, the study Visit, and pre- or post-decongestant (e.g., 01-001 V1 
pre-decongestant). 
 

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8.4 
ADVERSE EVENTS, ADVERSE DEVICE EFFECTS, SERIOUS ADVERSE EVENTS AND 
UNEXPECTED ADVERSE DEVICE EFFECTS 
In this study, the following types of adverse events will be collected and documented: 
 
• 
ClariFix Device-related Adverse Device Effects (ADE) 
• 
Cryotherapy procedure-related Adverse Events (AE) 
• 
Head, ear, nose, throat, and breathing/lung related AEs, including anticipated AEs 
• 
All Serious Adverse Events (SAE)  
• 
Unanticipated Adverse Device Effects (UADE)   
 
Anticipated adverse events are identified in the ClariFix IFU (See Appendix I). 
 
8.4.1 DEFINITION OF ADVERSE EVENTS (AE) 
An adverse event (AE) is any untoward medical occurrence in a subject who receives treatment with the 
study device, which does not necessarily have a causal relationship with this treatment. An adverse 
event (AE) can therefore be any unfavorable and unintended sign, symptom, or disease temporally 
associated with the treatment with the study device, whether or not related to the treatment or device. 
 
All AEs must be reported to the study sponsor. 
 
8.4.2 DEFINITION OF ADVERSE DEVICE EFFECT (ADE) 
Any adverse event related to the use of the study device. An adverse event is an untoward medical 
occurrence, unintended disease or injury, or untoward clinical sign in subjects. 
 
8.4.3 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition.  
 
8.4.4 DEFINITION OF UNEXPECTED ADVERSE DEVICE EFFECT (UADE) 
Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, the study 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 well-being of subjects. 
 
8.4.5 CLASSIFICATION OF AN ADVERSE EVENT 
8.4.5.1 SEVERITY OF EVENT 
For all adverse events (AEs), the following guidelines will be used to describe severity.  
 

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• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.4.5.2 RELATIONSHIP TO STUDY INTERVENTION 
All adverse events (AEs) must have their relationship to both the study device and study procedure 
assessed by the clinician who examines and evaluates the subject based on temporal relationship and 
his/her clinical judgment. The degree of certainty about causality will be graded using the categories 
below. In a clinical trial, the study product must always be suspect.  
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship to either the study 
device or the study procedure, and other possible contributing factors can be ruled out. The 
clinical event, including an abnormal laboratory test result, occurs in a plausible time 
relationship to study device or the study procedure and cannot be explained by concurrent 
disease or other drugs or chemicals. The event must be phenomenologically definitive. 
• 
Probably Related – There is evidence to suggest a causal relationship to either the study device 
or the study procedure, and the influence of other factors is unlikely. The clinical event, 
including an abnormal laboratory test result, occurs within a reasonable time after 
administration of the study intervention, is unlikely to be attributed to concurrent disease or 
other drugs or chemicals. 
• 
Potentially Related – There is some evidence to suggest a causal relationship to either the study 
device or the study procedure (e.g., the event occurred within a reasonable time after study 
procedure). However, other factors may have contributed to the event (e.g., the participant’s 
clinical condition, other concomitant events). 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to either the study device or the study procedure makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time after study 
procedure) and in which other drugs or chemicals or underlying disease provides plausible 
explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of either the study device or the study 
procedure, and/or evidence exists that the event is definitely related to another etiology. There 
must be an alternative, definitive etiology documented by the clinician. 
 
8.4.5.3 EXPECTEDNESS  
Sponsor will be responsible for determining whether an adverse event (AE) is expected or unexpected.  
An AE will be considered unexpected if the nature, severity, or frequency of the event is not consistent 
with the risk information previously described for the study intervention. 
8.4.6 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE), adverse device effect (ADE) or serious adverse event (SAE) may 
come to the attention of study personnel during study visits and interviews of a study participant 
presenting for medical care, or upon review by a study monitor. 
 

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Information to be collected includes event description, time of onset, clinician’s assessment of severity, 
relationship to study product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it may be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
Study site will record all reportable events with start dates occurring any time from treatment with the 
study device until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.  
At each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit.  
Events will be followed for outcome information until resolution or stabilization.] 
 
8.4.7 ADVERSE EVENT REPORTING  
AEs should be documented in the source documents at time of identification, and initial entry of all AEs 
into the EDC should be completed within 72 hours of identification.  Initial EDC entry may be pending 
additional information, but known information should be entered.  Source and EDC entry should be 
updated as new information becomes available and upon resolution of the AE. 
 
Additionally, Sponsor must be notified of SAE, SADE and UADE within 24-hours of identification via 
phone or email. 
 
8.4.8 SERIOUS ADVERSE EVENT REPORTING  
The study investigator shall complete an Adverse Event source form and email a copy of the form to 
sponsor within 24-hours of identification, in addition the AE reporting in section 8.4.7 should be 
followed.  If IRB notification is required, this should be completed as soon as possible, but in no event 
later than 10 working days after the investigator first learns of the effect.   
 
In the event of an unanticipated adverse device effect, the study sponsor is responsible for conducting 
an evaluation of any and shall report the results of such evaluation to the Food and Drug Administration 
(FDA) and to all reviewing IRBs and participating investigators within 10 working days after the sponsor 
first receives notice of the effect. Thereafter, the sponsor shall submit such additional reports 
concerning the effect as FDA requests. 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
Primary Efficacy Endpoints: 
 
H0: Change from Baseline (Delta) in rTNSS = 0 
 
H1: Change from Baseline (Delta) in rTNSS ≠ 0 
 

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Secondary Efficacy Endpoints: 
 
H0: Change from Baseline (Delta) = 0 
 
H1: Change from Baseline (Delta) ≠ 0 
 
9.2 
SAMPLE SIZE DETERMINATION 
Inasmuch as this is a feasibility study with N=30, no formal power and/or sample size estimations were 
performed.  The proposed sample size is comparable to those in other trials of this nature in this 
discipline. 
 
9.3 
POPULATIONS FOR ANALYSES 
There are two key populations for analyses: 
 
• 
The Safety Population is comprised of those subjects who received treatment by the ClariFix 
device 
• 
The Efficacy Population is comprised of those subjects in the Safety Population who also had at 
least one valid follow-up assessment. 
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
All statistical analyses will be performed using a two-sided hypothesis test at the overall 5% level of 
significance. P-values will be rounded to three decimal places. If a p-value is less than 0.001 it will be 
reported as “< 0.001.” If a p-value is greater than 0.999 it will be reported as “> 0.999.” No 
adjustments for multiplicity are planned. 
 
Continuous data will be summarized using descriptive statistics: n, mean, standard deviation or 
standard error, median, minimum and maximum. The decision to use either standard deviation or 
standard error will be based upon the objective of the presentation: standard deviation will be used 
when the interest is the natural variability of the data; standard error will be used when comparing 
two or more means. Continuous variables that are recorded using approximate values (e.g., < or >) 
will be replaced by the closest exact value for the calculation of summary statistics. 
 
Categorical variables will be summarized using frequency counts and percentages. 
 
For ordinal-scaled variables, a combination of the above may be employed as appropriate: 
frequency and percentage of observations within a category and means and standard deviations of 
the scores of the categories. 
 
For categorical and ordinal variables, percentages will be calculated based on non- missing 
data. 
 
All analyses will be based on available data; no imputation for missing data will be conducted. 
 
Baseline is defined as the last measurement for the outcome of interest obtained before the 
exposure to the study device. 
 

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Duration variables will be calculated using the general formula: [(end date – start date) +1] 
 
Within-subject changes will be calculated as visit value minus baseline value such that a negative change 
reflects a decrease and a positive change signifies an increase. No judgment (“better” or “worse”) is 
associated with the sign of the change, only direction. The Wilcoxon Signed Rank test will be used to 
test the null hypothesis that the mean (or median) within-subject change is equal to zero.  
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
For the purposes of formality, rTNSS has been designated as the primary efficacy endpoint.  However, 
since this is, in fact, a feasibility study, any of the secondary endpoints described below may be 
promoted in the next study to primary status.  Therefore, the analytical approach for all efficacy 
endpoints will be identical. 
 
The objective of these analyses is to present the changes from baseline for a small sample size in a 
manner that is statistically sound and intuitively comprehensible.  To that end the tables will present 
summary statistics for the Baseline, 7-Day, and 1- and 3-Month timepoints, as well as serial changes 
from baseline.   
 
The statistical null hypothesis is that the deltas are distributed around zero change.  Wilcoxon Signed 
Rank tests will be employed to evaluate whether the deltas are distributed around zero or shifted either 
positively or negatively away from zero.  No adjustments for multiplicity are planned since this is a 
feasibility or proof of concept study. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
The secondary endpoints are changes over time in: 
• 
NOSE Survey 
• 
SNOT-22 
• 
MiniRQLQ 
• 
VAS – nasal symptoms 
• 
CGI-I 
• 
Physician Assessment of congestion 
• 
Physician Assessment of turbinate hypertrophy 
 
The analytical approach is described in the section above for the Primary Endpoint. 
 
9.4.4 SAFETY ANALYSES 
The overall incidence (i.e., number and percent of subjects with 1 or more adverse event) of adverse 
events, serious adverse device events, serious adverse events, and device and/or procedure related 
events (e.g., possibly, probably or definitely related) will be calculated from time of treatment through 
the entire duration of follow-up. The overall incidence of mild, moderate and severe events will be 
calculated by considering the most severe event for each subject. 
 
In addition, the overall incidence for each adverse event type will be calculated. The adverse event types 
will be classified as defined in Section 8.4. 
 
 
 

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9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Baseline characteristics, including demographic characteristics, medical history, patient-reported 
outcomes and physical measurements will be summarized using descriptive statistics.  
 
9.4.6 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Listings of adverse events may be produced. 
 
9.4.7 EXPLORATORY ANALYSES 
Visual severity of nasal congestion and turbinate hypertrophy will be evaluated for each side of the nasal 
cavity separately.  Screening, 1- and 3-Month timepoint scores will be cross-tabulated, and the 
proportion with improvement will be calculated. 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT DOCUMENTS PROVIDED TO PARTICIPANTS 
An Informed Consent Form (ICF) describing in detail the study treatment and study device, study 
procedures, and risks are to be given to each participant and written documentation of informed 
consent is required prior to initiating any study-related activities.   
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator, or qualified designee, will explain the research study to the participant and answer any 
questions that may arise. A verbal explanation will be provided in terms suited to the participant’s 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research participants.  Participants will have the opportunity to carefully review the written consent 
form and ask questions prior to signing. The participants should have the opportunity to discuss the 
study with their family or think about it prior to agreeing to participate. The participant will sign the 
informed consent document prior to any procedures being done specifically for the study. Participants 
must be informed that participation is voluntary and that they may withdraw from the study at any 
time, without prejudice. A copy of the informed consent document will be given to the participants for 
their records. The informed consent process will be conducted and documented in the source document 
(including the date), and the form signed, before the participant undergoes any study-specific 
procedures. The rights and welfare of the participants will be protected by emphasizing to them that the 
quality of their medical care will not be adversely affected if they decline to participate in this study. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
The sponsor may choose to temporarily suspend or prematurely terminate study or a study site with or 
without cause.  Written notification, documenting the reason for study suspension or termination, will 
be provided by the sponsor, as applicable, to the investigator and IRB.   
 

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If the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform, 
as applicable, study participants, the Institutional Review Board (IRB), and sponsor and will provide the 
reason(s) for the termination or suspension.  Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study and/or study site may resume once concerns about safety, protocol compliance, and data quality 
are addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s). This confidentiality is extended to cover the clinical information relating to 
participants. Therefore, the study protocol, documentation, data, and all other information generated 
will be held in strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) 
and pharmacy records for the participants in this study. The clinical study site will permit access to such 
records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored with the sponsor.  This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by 
clinical sites and by Arrinex research staff will be secured and password protected.  
 
10.1.4 CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with International 
Conference on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s).   
 

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A risk-based approach to monitoring will be utilized and details of clinical site monitoring will be 
documented in a Clinical Monitoring Plan (CMP). The CMP will describe in detail who will conduct the 
monitoring, at what frequency monitoring will be done, at what level of detail monitoring will be 
performed, and the distribution of monitoring reports.  An increased level of monitoring may be utilized 
either at an individual site or for the study as a whole in the event of, but not limited to, data quality 
issues or increased incidence of AEs. 
 
10.1.5 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data collection, 
documentation and completion.  An individualized quality management plan will be developed to 
describe a site’s quality management.] 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated and biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Manufacturing Practices (GMP)).  
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities. 
 
10.1.6 DATA HANDLING AND RECORD KEEPING  
 
10.1.6.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) will be entered into Medrio (https://medrio.com), a 21 CFR Part 11-compliant data capture system 
provided by the Sponsor. The data system includes password protection and internal quality checks, 
such as automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
Clinical data will be entered directly from the source documents. 
 
 
 

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10.1.6.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 2 years after the close-out of the study and until 
there are no pending or contemplated marketing applications. These documents should be retained for 
a longer period, however, if required by local regulations. No records will be destroyed without the 
written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform the 
investigator when these documents no longer need to be retained. 
 
10.1.7 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within five (5) working days of identification of the protocol deviation, or within five (5) 
working days of the scheduled protocol-required activity.  All deviations must be addressed in study 
source documents, reported to the Sponsor.   
 
Protocol deviations must be sent to the reviewing Institutional Review Board (IRB), when applicable per 
their policies. The site investigator is responsible for knowing and adhering to the reviewing IRB 
requirements. Further details about the handling of protocol deviations will be included in the MOP.  
 
10.1.8 FINANCIAL DISCLOSURE 
Investigators shall provide financial disclosure according to applicable regulations. 
 
 
 

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10.2 ABBREVIATIONS 
 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
CFR 
Code of Federal Regulations 
CGI-I 
Clinical Global Impression--Improvement 
CMP 
Clinical Monitoring Plan 
CRF 
Case Report Form 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
HIPAA 
Health Insurance Portability and Accountability Act  
ICH 
International Conference on Harmonisation  
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MiniRQLQ 
Mini Rhinoconjunctivitis Quality of Life Questionnaire 
MOP 
Manual of Procedures 
NOSE 
 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
RQLQ 
Rhinoconjunctivitis Quality of Life Questionnaire 
rTNSS 
Reflective Total Nasal Symptom Score 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SAP 
Statistical Analysis Plan 
SNOT-22 
Sino-nasal Outcome Test 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
UADE 
Unanticipated Adverse Device Effect 
US 
United States 
UV 
Unscheduled Visit 
VAS 
Visual Analog Scale 
NRS 
Numeric Rating Scale 
 
 
 

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12 APPENDIX I