Clinical trial NCT03591068
Conditions: Nasal Polyposis
Sponsor: Optinose US Inc.
Start date: 2018-06-07; Completion date: 2019-02-22
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a 24-week, open-label, multi-center study designed to assess the efficacy and safety of OPN-375 186 μg twice a day in subjects with nasal polyps using Nasoendoscopic video. The total planned number of subjects is approximately 10, with each subject receiving OPN-375 186 μg twice a day.

Detailed description:
The primary objective of this study is to evaluate the efficacy and safety of OPN-375 186 μg twice a day in adults with Bilateral Nasal Polyps using Nasoendoscopic video. The secondary objectives of this study are to evaluate the safety of OPN-375 via adverse event reports, vital signs, and nasal examination. In addition, to measure any change in subject symptoms and functioning from Baseline to 12 and 24 weeks during the study, using the Sinonasal Outcome Test -22 (SNOT-22), Patient's Global Impression of Change (PGIC), and measurement of nasal polyps by independent, blinded reader, and any changes throughout the study.

Arms: arm 1: None
Interventions: intervention 1: Fluticasone Propionate
Intervention descriptions: intervention 1: OPN-375 186 μg BID, Delivered via exhalation delivery system

Protocol documents:
ICF_001.pdf: 
 
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INFORMED CONSENT TO TAKE PART IN A RESEARCH 
STUDY 
 
TITLE: 
A 24-Week Open-Label Study Evaluating the Efficacy and Safety of 
OPN-375 186 µg Twice a Day (BID) in Adults with Bilateral Nasal 
Polyps using Nasoendoscopic Video 
 
PROTOCOL NO.: 
OPN-FLU-NP-3104 
 
WIRB® Protocol #20180279 
 
SPONSOR: 
OptiNose US, Inc 
 
INVESTIGATOR: 
Name 
 
Address 
 
City, State Zip 
 
Country 
 
STUDY-RELATED 
PHONE NUMBER(S): 
Name 
 
Number(s) (24-hour phone number required) 
 
What is the purpose of this form? 
 
You are being asked to participate in a research study. It is important that you read the following 
explanation of the proposed procedures. This form describes the purpose, procedures, benefits, 
risks, discomforts and precautions of the study. It also describes the alternative procedures that 
are available to you and your right to withdraw from the study at any time. A member of the 
study staff will read through the consent with you and discuss all the information. When you 
think you understand the study, you will then be asked if you agree to take part. If you agree, 
you will be asked to sign this consent form. Once you sign it, we will give you a signed and 
dated copy to keep. 
 
You may show this consent form to family, other doctors, and friends before you sign it. You 
may want to discuss it with them to help you decide if you want to be part of the study. If you do 
not know another doctor, but want a second opinion about this study, please ask. The study 
doctor will give you the name of another doctor that you can talk to. 
 
You are being asked to participate in this study because you have been diagnosed with nasal 
polyps in both sides of your nasal cavities. 
 
Why is this study being done? 
 
This study is being conducted to see if OPN-375 (fluticasone propionate nasal spray with an 
exhalation delivery system that delivers drug into the nose) is safe and effective in reducing your 
nasal symptoms and the size of your nasal polyps, and to provide video evidence of the changes 
that occur over time with OPN-375 treatment.  The sponsor will pay the study doctor for conducting 
this study and for your participation. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
 


 
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What is being studied? 
 
Currently, the most commonly used medications for the treatment of nasal polyps and their 
symptoms are part of a class of medications called corticosteroids.  Corticosteroids are natural 
substances found in the body that help fight inflammation.  Fluticasone propionate is a man-
made corticosteroid. 
 
Fluticasone propionate given at a dose of 186 mcg twice a day using the exhalation delivery 
system is being used in this study. This study seeks to document the response of your polyps by 
documenting the change in the size of your nasal polyps, and to provide video evidence of the 
changes that occur over time. The documentation of polyp change over time is not done routinely 
and is therefore considered investigational. 
 
OPN-375 (fluticasone propionate) is approved by the FDA as XHANCE™ for the treatment of 
nasal polyps in adults.  The approved doses are one or two sprays per nostril twice daily (total 
daily dose of 372-744 micrograms). 
 
The delivery system has a nose piece and mouthpiece and a glass bottle that contains the study 
medication. The user administers the medication by inserting the nosepiece into one nostril and 
the mouthpiece into the mouth.  The user then blows forcefully into the mouthpiece while pushing 
up on the bottom of the glass bottle. The medication then flows into the nasal cavity. The 
procedure is repeated in the other nostril. You will use the study medication twice a day, in the 
morning and at night. You will receive detailed instructions on the number of sprays and how to 
properly use the device. 
 
What do you need to know about this study? 
 
Approximately 10 patients are expected to take part in this study at 2 US sites.  The entire study 
is expected to last for about 24 weeks. Your participation in the study will last up to 24 weeks. 
 
What will happen during this study? 
 
PROCEDURES TO BE FOLLOWED DURING THE 
STUDY 
 
Visit 1 (Day 1/Baseline) 
 
If you decide you want to be in the study, you will have the following procedures, called 
“screening procedures,” performed to find out if you qualify to be in this study.  This visit will 
last about 2 hours. 
 
• 
The study staff will review with you your medical history including a review of your 
current medications.  You will not be permitted to take or use certain medications 
while you are in the study. It is important that you inform your study doctor or 
research staff of all prescription and nonprescription medications, dietary 
supplements and vitamins which you are presently taking or have taken within the 
past 1 month.  If you have asthma or chronic obstructive pulmonary disease 
(COPD) you will be asked about medications, you have taken within the past 3 
months. 


 
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• 
The study staff will review inclusion/exclusion criteria (study rules) with you. 
• 
You will receive instruction on the use of OPN-375. You will be given a training 
device that contains no active medication and the study staff will evaluate your 
ability to correctly use the device. You will return the training device to the study 
staff. 
• 
If you are a woman who can have children, a urine pregnancy test will be 
performed.  If you are pregnant (test positive) you will not be allowed to participate 
in the study. 
• 
Your vital signs (blood pressure and heart rate) will be measured. 
• 
You will complete a questionnaire that consists of 22 questions related to the 
symptoms of and how you feel about your nasal polyps.  This questionnaire takes 
less than 5 minutes to complete 
• 
A test for your sense of smell will also be conducted.  You will smell, either 
blindfolded or with open eyes, pens with different odors.  The substances used are 
all non-toxic and not harmful in the concentrations given.  If you are unable to smell 
and cannot decide on an answer, please use your best guess.  There are three 
parts to the test which will take about a total of 30-40 minutes to complete. 
• 
A nasal examination will be performed and a nasoendoscopy will be performed 
using a nasoendoscope.  The nasoendoscope is a long thin tube with a bright light 
at the end. It allows your doctor to look at the nasal passages and other 
surrounding structures.  This procedure is done with you sitting in a chair with a 
head support. Your doctor will decide if you will require the use of a local anesthetic 
(applied directly to the area) and / or a decongestant before the nasoendoscopy is 
performed.  Your doctor will insert the endoscope into your nostril(s) and through 
the nasal passages. Your doctor will observe, record, and grade the nasal polyps 
that are present, and will record the nasal examination. An independent doctor will 
also grade the polyps based on the video recording of the nasal examination.  The 
video recording viewed by the independent doctor will not have your name on it. 
 
If you qualify for the study after screening procedures during the Day 1/Baseline visit, you will 
be given a 3-month supply of the study medication and your study staff will review the proper 
use of the device with you.  You will give yourself morning and evening doses of the study 
medication as directed by the study team and the instructions provided. 
 
At each visit you must bring back your study medication. 
 
Study Staff will contact you approximately every 4 weeks between site visits to confirm if you are 
taking your medication as instructed, to inquire if you have had any changes in your health and 
to record changes in your medications since your last visit. 
 
Visit 2 (Week 12) 
 
At this visit the study staff will ensure that you are still eligible to continue participating in 
the study.  This visit will last about 2 hours. 
• 
Your study team will review any changes in your health and changes in your 
medications since your last visit. 
• 
If you are a woman who can have children, a urine pregnancy test will be 
performed; you will be told if you are pregnant and will not be able to continue your 
participation in the study. 
• 
Your vital signs (blood pressure and heart rate) will be measured. 
• 
You will complete a questionnaire that consists of 22 questions related to the 
symptoms of and how you feel about your nasal polyps.  The questionnaire takes 
approximately 5 minutes to complete 


 
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• 
You will complete a questionnaire about your overall impression of the changes in 
your symptoms that takes less than 5 minutes to complete 
• 
A nasal examination will be performed and a nasoendoscopy will be performed 
using a nasoendoscope.  The nasoendoscope is a long thin tube with a bright light 
at the end. It allows your doctor to look at the nasal passages and other 
surrounding structures.   This procedure is done with you sitting in a chair with a 
head support. Your doctor will decide if you will require the use of a local anesthetic 
(applied directly to the area) and / or a decongestant before the nasoendoscopy is 
performed.  Your doctor will insert the endoscope into your nostril(s) and through 
the nasal passages. Your doctor will observe and record the nasal polyps that are 
present, including a video recording of the nasal examination. An independent 
doctor will also grade the polyps based on the video recording of the nasal 
examination.  The video recording viewed by the independent doctor will not have 
your name on it. 
• 
Your study staff will review the proper use of the device with you. 
• 
You must bring back your study medication and you will receive new medication. 
 
Study Staff will contact you approximately every 4 weeks between site visits to confirm if you are 
taking your medication as instructed, to inquire if you have had any changes in your health and 
to record changes in your medications since your last visit. 
 
Visit 3 (Week 24) 
 
During this visit the following procedures will be performed.  This visit will last about 2 hours. 
 
• 
Your study team will review any changes in your health and changes in your 
medications since your last visit. 
• 
If you are a woman who can have children, a urine pregnancy test will be 
performed; you will be told if you are pregnant. 
• 
Your vital signs (blood pressure and heart rate) will be measured. 
• 
You will complete a questionnaire that consists of 22 questions related to the 
symptoms of and how you feel about your nasal polyps.  The questionnaire takes 
approximately 5 minutes to complete. 
• 
You will complete a questionnaire about your overall impression of the changes in 
your symptoms that takes less than 5 minutes to complete 
• 
A test for your sense of smell will also be conducted.  You will smell, either 
blindfolded or with open eyes, pens with different odors.  The substances used are 
all non-toxic and not harmful in the concentrations given.  If you are unable to smell 
and cannot decide on an answer, please use your best guess.  There are three 
parts to the test which will take about a total of 30-40 minutes to complete. 
• 
A nasal examination will be performed and a nasoendoscopy will be performed 
using a nasoendoscope.  The nasoendoscope is a long thin tube with a bright light 
at the end. It allows your doctor to look at the nasal passages and other 
surrounding structures. This procedure is done with you sitting in a chair with a 
head support. Your doctor will decide if you will require the use of a local anesthetic 
(applied directly to the area) and / or a decongestant before the nasoendoscopy is 
performed.  Your doctor will insert the endoscope into your nostril(s) and through 
the nasal passages. Your doctor will observe and record the nasal polyps that are 
present, including a video recording of the nasal examination.   An independent 
doctor will also grade the polyps based on the video recording of the nasal 
examination.  The video recording viewed by the independent doctor will not have 
your name on it. 
• 
You will return your study medication. 
 


 
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What is being performed specifically for the study? 
 
The following are being performed for the purposes of this study and are not considered standard 
care: 
 
Urine Pregnancy tests (for women who can become pregnant), additional office visits, completion 
of questionnaires and the smell tests. 
 
Other Important Information/ Participant Responsibilities 
 
If you decide to take part in this research study, you will be expected to complete the study visits 
and other procedures and to follow the instructions of the study doctor and study staff.  It is 
important that you follow the study doctor’s instructions for taking the study medication and that 
you do not give the study medication to anyone else. 
 
If you require a reading aid to read/write (e.g. glasses), kindly ensure that you bring such aids 
with you to all study visits, to assist with the completion of the questionnaires. 
 
During your participation in the study you will receive your assigned study medication for the time 
that you are actively participating in this research study; however, the study medication will not be 
made available to you after your participation in this research study ends. 
 
If you decide to stop participating in the study, it is important that you notify the study doctor or 
study staff.  You will be asked to return to the study center for a final study visit. 
 
What are the potential risks of being in the study? 
 
UNKNOWN RISKS TO PREGNANT WOMEN, EMBRYO, FETUS OR NURSING INFANT 
 
Use of the study medication may involve unknown risks to a pregnant woman, an embryo, fetus 
(unborn baby), or nursing infant.  Therefore, if you are pregnant, planning to become pregnant 
or are lactating (including breastfeeding a child), you cannot participate in this study. 
 
If you are a woman who could become pregnant, you must either be abstinent (not have sexual 
intercourse) or you must use birth control during your study participation.  The following methods 
of birth control are acceptable during participation in the study: 
 
• 
prescription oral contraceptives (the Pill), 
• 
contraceptive injections, 
• 
contraceptive patch, 
• 
intrauterine device, 
• 
double-barrier method defined as condoms, diaphragm, or cervical cap with spermicidal 
foam, cream, or gel (the cervical cap, even with spermicidal foam, cream or gel is not as 
effective as other options), 
• 
or female study participants whose male partner is sterile. 
 
If you are postmenopausal, but for less than 1 year, meaning that you have had menstrual 
bleeding within the 1 year before entry into this study, you will be required to have pregnancy 
tests and must use birth control if sexually active. 
 
Your study doctor will discuss with you whether the methods of birth control you plan to use are 
acceptable for this study. 
 


 
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Before entering the study, a urine pregnancy test will be done for all women who are able to 
become pregnant.   This test might not detect an early pregnancy.  Urine pregnancy tests will 
be repeated at each office visit.   If you think you are pregnant, tell the study doctor 
immediately. 
 
Pregnancy will be a reason to stop study treatment.  If you become pregnant during the study, 
you will be discontinued from study participation for safety reasons.  If you become pregnant, 
please make your obstetrician aware of your study participation. 
 
POSSIBLE SIDE EFFECTS OF OPN-375 
 
Nose Problems 
 
Nose problems may include: nose bleeds, sores (ulcers) in your nose, a certain fungal infection in 
your nose, mouth, and/or throat (thrush), and hole in the cartilage of your nose (nasal septal 
perforation).  Symptoms of nasal septal perforation may include: crusting in the nose, nose bleeds, 
runny nose, and whistling sound when you breathe. 
 
Slow Wound Healing 
 
The use of fluticasone may slow wound healing in your nose.  You should let the study doctor 
know if you have a sore in your nose, have had surgery on your nose, or if your nose has been 
injured. 
 
Eye Problems 
 
Glaucoma and cataracts have been reported with long term use of corticosteroids.  You should let 
the study doctor know if you have any eye problems and if you experience any change in your 
eyesight. 
 
Serious Allergic Reactions 
 
You should let your study doctor know or get emergency medical care (call 911 or go to the 
nearest emergency room) if you get any of the following signs of a serious allergic reaction:  rash, 
hives, swelling of your face, mouth, and tongue, and breathing problems.  These reactions might 
become very serious and even life-threatening.   If you have a history of hypersensitivity to any 
medications you should let your doctor know so s/he can decide if it is safe for you to participate in 
this study. 
 
Weakened Immune System and Increased Chance of Getting Infections 
(Immunosuppression) 
 
Taking corticosteroids such as fluticasone propionate may make you more likely to get infections 
and can make certain infections worse. These infections may include tuberculosis (TB), ocular 
herpes simplex infections, and infections caused by fungi, bacteria, viruses, and parasites. Avoid 
contact with people who have a contagious disease such as chickenpox or measles while using 
OPN-375. If you meet someone who has chickenpox or measles call your study doctor right away. 
Symptoms of an infection may include: fever, pain, aches, chills, feeling tired, nausea, vomiting. 
 
Reduced Steroid Hormone Levels (adrenal insufficiency). 
 
Adrenal insufficiency happens when your adrenal glands do not make enough steroid hormones. 
This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and 
start taking medicine containing a topical steroid (such as OPN-375). Symptoms of adrenal 
insufficiency may include: feeling tired, lack of energy, weakness, nausea and vomiting, and low 
blood pressure. 
 


 
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Bone Thinning or Weakness (Osteopenia or osteoporosis) 
 
Most Common Side Effects 
 
The most common side effects of OPN-375 include: nose bleeds, redness or sores (ulcers) in the 
nose, nasal congestion, headache, sinus infection, sore nose and throat, and sore throat. 
 
Drug interactions with Fluticasone 
 
Certain medications may interact with OPN-375.  It is important that you inform your study doctor 
or research staff of all medications you are currently taking. 
 
Other possible discomforts from participating in this study 
 
The nasal endoscopy may activate the gag reflex (i.e. make you feel like you are choking or going 
to vomit).  Nosebleed, nasal discomfort, spasms, and cough may also occur. Let your doctor know 
if you are experiencing any unpleasant symptoms during the procedure. 
 
Will you be informed of new information relating to the study? 
 
All new findings discovered during the course of this research study that may reasonably influence 
your decision to continue to participate in this study will be provided to youby your study doctor as 
such information become available. 
 
Does being in this study provide any benefit? 
 
Participating in this study may or may not provide a direct benefit to you. It is hoped that the 
information learned in this research may benefit future patients with nasal polyps. 
 
Who do you contact in the event of an emergency? 
 
If you suffer any medical events that are not typical for you during this study, the events would 
be considered an “adverse event”. Adverse events are not necessarily side effects of the study 
medication. For example, a person might have an upset stomach due to receiving a study 
medication, or the upset stomach might occur without the study medication.  We will watch 
everyone in the study for any adverse events. 
 
You will be monitored very closely by the study doctor and medical staff while you are in the study. 
This monitoring will include vital signs, nasal examinations, and other tests if the study doctor feels 
that they are needed. 
 
It is important that you tell the study staff if you feel abnormal or unusual in any way. If you are not 
completely truthful about any side effects, you may increase the risk of harming yourself by taking 
part in this study. You will be given any new information that may affect your willingness to start or 
continue in the study. 
 
If you experience an adverse reaction or a research-related injury during the course of the 
study, you should immediately contact Dr. [Name] at [Number] or [Number] (if during non-
business hours). 
 
If you seek emergency care, or if you are hospitalized, please alert the doctor who is treating 
you that you are enrolled in a research study being conducted by Dr. [Name]. 
 


 
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What happens if you have a research related injury? 
 
If you suffer a physical injury as a result of your participation in this study, you will be reimbursed 
for medical expenses to treat the injury, to the extent not paid by your insurance or if you do not 
have insurance.  You may receive medical care in the same way as you would normally. No 
funds have been set aside for payments or other forms of compensation (such as for lost 
wages, lost time, or discomfort).  However, you do not give up any of your legal rights by signing 
this consent form. 
 
What other treatments are available? 
 
Alternative Treatments 
 
Your alternative to taking part in this study is to receive standard medical care as prescribed by 
your doctor.  The following treatments are available for nasal polyps: 
 
• 
nasal corticosteroid spray 
• 
oral corticosteroids such as prednisone 
• 
Sometimes, nasal polyps are so large and obstructive that corticosteroid nasal sprays 
are ineffective. In such cases, surgery can be an effective option. 
 
Your study doctor will be able to discuss alternative procedure(s) or treatment(s) that may be 
available, and their potential benefits and risks. 
 
Will it cost you anything to be in this study? 
 
The study medication will be made available to you at no charge and you will not pay for any 
protocol-related tests and procedures during your participation in the study. You and/or your 
insurance provider may be billed for any standard medical care that is not part of this research 
study. 
 
Will you be paid for being in this study? 
 
To help defray any costs associated with your participation (for example, travel costs), you will be 
paid $50.00 per each completed visit up to a total of $150.00 for completing the entire study. If you 
should not complete the study, you will be paid for each of the visits you have completed. 
 
The Investigator/Study doctor will receive compensation from the Sponsor to conduct this research 
study. 
 
Do you have to be in this study? 
 
Your participation in this study is voluntary.  Your refusal to participate or your withdrawal from 
the study will involve no penalty or loss of benefits to which you are entitled.  You may stop your 
participation at any time without affecting your ongoing medical care.  If you decide to stop 
participating in the study, it is important that you notify the study doctor or study staff.  You will 
be asked to return to the study center for a final study visit. 
 


 
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Can you be removed from the study without your permission? 
 
Your study doctor may end your participation in this study for any of the following reasons: 
 
1. If you develop a side effect or medical condition that may place you at risk of 
further complications by continuing your participation or if you need a medicine not 
allowed on this study; 
2. If you become pregnant; 
3. If you are unable to take the study medication 
4. If you are unable to keep your scheduled appointments; 
5. If the study is cancelled by the sponsor, the Institutional Review Board/ Ethics 
Committees, FDA or any other Regulatory Authority. 
6. For administrative reasons. 
 
Who will have access to your study and/or medical information? 
 
Records of your participation in this study will be held confidential except as disclosure is required 
by law or as described in this informed consent document. Disclosures required by law may 
include: suspected child abuse; infectious disease; expression of suicidal ideas; those situations 
in which research documents are ordered to be produced by a court of law; and those situations 
in which researchers are required to report to the appropriate authorities.  The study doctor, the 
sponsor or persons working on behalf of the sponsor and under certain circumstances, 
representatives of the FDA, Institutional Review Board (IRB), and other Regulatory Authorities 
will be able to inspect and copy confidential study-related records which identify you by name.  
Therefore, absolute confidentiality cannot be guaranteed.  If the results of this study are 
published or presented at meetings, you will not be identified. 
 
Who do you contact if you have questions about the study? 
 
Your study doctor will answer any questions regarding OPN-375, fluticasone propionate, its 
risks, side effects, potential benefits, and other treatment options available to you now or at 
any time you are taking part in this study. 
 
PRIVACY: COLLECTION, USE AND DISCLOSURE OF IDENTIFIABLE PRIVATE HEALTH 
INFORMATION 
 
During your participation in this research study, the study doctor and study staff will collect or 
create personal health information, such as documentation of medical histories, physical 
examination, etc., about you. The study doctor will keep this personal health information in your 
study-related records.  In addition, the study doctor may obtain, and include in your study- 
related records, information about your past, present and/or future physical or mental health 
and/or condition. (Your study doctor may ask you or your legally acceptable representative to 
sign a separate consent/release to obtain some or all of your medical records from your 
doctor(s) or other healthcare provider(s).)  Your study-related records may include other 
personal information, medical record number(s), or any other identifying health information 
number, initials, date of birth, etc., that could be used to identify you.  (Health information that 
contains information that can be used to identify you will be called “Identifiable Private Health 
Information” or “IPHI.”). 
 
The IPHI to be collected, used and disclosed during this study includes: physical examinations, 
medical history and other data collected during this study. 
 


 
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If you do not agree to share your IPHI you will not be able to participate in this study. By signing 
this consent document, you are giving the study doctor permission to disclose your IPHI to: 
 
• 
The sponsor of this study and anyone working on behalf of the sponsor to conduct this 
study (“sponsor’).  The sponsor will analyze and evaluate the data that may contain your 
IPHI and may use it to develop new tests, procedures and commercial products.  The 
study staff will assign a code number and/or letters to your study-related records which 
mean that you will not ordinarily be identified in the records sent to the sponsor.  The 
sponsor may, however, look at your complete study records that identify you.  In addition, 
the sponsor may visit the study site to oversee the way the study is being conducted and 
may review your IPHI during these visits to make sure the information is correct. 
• 
The Institutional Review Board (“IRB”) may have access to your IPHI in relation to its 
responsibilities as an Institutional Review Board. 
• 
Clinical monitors and auditors, who work for the study sponsor, will have access to all 
information about you at the study site, so that they can verify the information.  Also, the 
study sponsor might review or copy all your records, including the above information, to 
assure the quality of the study or for other uses allowed by law. 
 
The study doctor or sponsor may disclose your IPHI to the FDA and/or similar government 
agencies in other countries. 
 
Except for the disclosures described above, your IPHI will not be shared with others unless 
disclosure is otherwise required by law, for example, if a court of law orders the disclosure.   If 
you have questions about this, please ask the study doctor. 
 
Your consent to collect, use and disclose IPHI will expire fifty (50) years from the date you sign 
it unless you cancel it sooner. You can cancel your consent to collect, use and disclose your 
IPHI at any time.  To do so, you must write a letter to the study doctor stating that you are 
revoking your consent to collect, use and disclose your identifiable private health information.  If 
you cancel your consent allowing the study doctor to collect, use and disclose your IPHI, you 
will not be allowed to continue in the study.  The study doctor will no longer use or share your 
IPHI unless it is necessary to protect the integrity of the study. 
 
There are national and provincial/territorial laws that require the study doctor to protect the 
privacy of your IPHI; however, there is no guarantee of absolute privacy because of the need to 
share information.  After disclosure of your IPHI, the laws may no longer protect the privacy of 
your information. The sponsor or others may share your information with other people who are 
not required to protect the privacy of your information. 
 
If you would like to know how the sponsor will protect the privacy of your records, ask the study 
doctor how to get this information. 
 
You have a right to see and make copies of your study-related information.  By signing this 
consent document, however, you agree not to see or copy some or all your records until the 
sponsor has completed all work related to this study.   At that time, you may ask to see your 
records. 
 


 
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VOLUNTEER'S STATEMENT: 
 
I have been given a chance to ask questions about this research study.  These questions have 
been answered to my satisfaction.  I may contact Dr. [Name] at the phone number listed above on 
the first page if I have any more questions, concerns, or complaints about taking part in this study.  I 
understand that Dr. [Name] or the company he/she is employed by is being paid by the sponsor for 
my participation in this study. 
 
I understand that my participation in this research project is voluntary.  I know that I may quit the 
study at any time without harming my future medical care or losing any benefits to which I might 
be entitled.  I also understand that the investigator in charge of this study may decide at any 
time that I should no longer participate in this study. 
 
This study has been reviewed and approved by the Western Institutional Review Board® (WIRB®). 
If you have any questions, concerns or complaints about this study, or questions about your rights 
as a research participant-, or the Investigator’s responsibilities, you may contact WIRB 24 hours per 
day and 7 days per week at 360-252-2500 or toll-free at 1-800-562-4789. An IRB is a group of 
scientific and non- scientific individuals who perform the initial and ongoing ethical review of the 
research study with the subject’s rights and welfare in mind.  If you have any study-related 
comments, complaints or concerns, we ask that you first contact the study investigator. Please call 
the IRB if you need to speak to a person independent from the Investigator and the research staff, 
and/or if the Investigator and the research staff could not be reached. 
 
By signing this form, I have not waived any of my legal rights. 
 
I have read and understand the above information.  I agree to participate in this study.  I 
understand that I will be given a copy of this signed and dated form for my own 
records. 
 
 
 
 
 
 
 
 
Printed Name of Study Participant  
Signature of Participant 
Date 
 
 
 
 
 
 
 
 
 
 
Printed name of the person explaining 
Signature of person explaining 
Date 
the consent 
the consent 
 
 
 
 
 
 
 
 
Printed name of Investigator 
Signature of Investigator 
Date 

Prot_SAP_002.pdf: 
OptiNose US, Inc.  
 
 
1 
 
 
Confidential and Proprietary 
Protocol Number OPN-FLU-NP-3104 
 
Amendment 1/ Version 1 /dated 30Jan2018 - FINAL 
1 
TITLE PAGE 
CLINICAL STUDY PROTOCOL  
A 24-Week Open-Label Study Evaluating the Efficacy and Safety of OPN-375 186 μg 
Twice a Day (BID) in Adults with Bilateral Nasal Polyps using Nasoendoscopic Video 
 
Sponsor: 
OptiNose US, Inc. 
 
Protocol Number: 
OPN-FLU-NP-3104 
Name of Study: 
VISUALIZE 
EudraCT Number 
N/A 
Development Phase: 
IIIb 
 
 
Protocol Version/Date: 
Amendment 1, Version 1, dated 30 Jan 2018 
 
 
 
 
 
 
 
 
 
 
 
STATEMENT OF CONFIDENTIALITY: 
This document contains scientific and commercial information proprietary to 
OptiNose US, Inc. that is privileged or confidential and is intended solely for the purpose of 
this clinical investigation. It should be kept secure and its contents should not be disclosed to 
any third party without the prior written consent of OptiNose. 
 
 


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Protocol Number OPN-FLU-NP-3104 
 
Amendment 1/ Version 1 /dated 30Jan2018 - FINAL 
VERSION HISTORY 
Version 
Explanation of Change(s) and Reason/Justification for 
Changes 
Date 
0 
Original Protocol 
16 Jan 2018 
1 
Updated Title Page to reflect “Protocol Version/Date” 
Added Version History 
Section 3 and 13.3 added Urine Pregnancy Test to Visit 2 
Section 6.1 and 10.1 - Removed the word “well” from 
“shake well” to ensure consistency with Instructions for Use  
Corrected minor formatting issues 
30 Jan 2018 
 




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Signature Page for Principal Investigator:   
Protocol No. OPN-FLU-NP-3104 
 
Title:  A 24-Week Open-Label Study Evaluating the Efficacy and Safety of OPN-375 186 μg 
Twice a Day (BID) in Adults with Bilateral Nasal Polyps using Nasoendoscopic Video 
 
Name of Study: 
VISUALIZE 
 
 
 
I have read this protocol and agree to conduct this study in accordance with all stipulations of 
the protocol and in accordance with the accepted version of the Declaration of Helsinki. 
 
 
Principal Investigator Name: 
(Printed) 
 Signature:  
 
Date: 
 
 
 
 
 
 
 


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2 
SYNOPSIS   
TITLE OF STUDY: A 24-Week Open-Label Study Evaluating the Efficacy and Safety of OPN-375 186 μg 
Twice a Day (BID) in Adults with Bilateral Nasal Polyps using Nasoendoscopic Video 
Name of Study: VISUALIZE 
SPONSOR: OptiNose US, Inc. 
DEVELOPMENT PHASE: 3b 
EudraCT Number: N/A 
STUDY OBJECTIVES:  
Primary:  The primary objective of this study is to document the changes in polyp burden over time using 
nasoendoscopic video. 
Secondary: Secondary objectives of this study include: 
• 
Evaluate the safety of OPN-375 via adverse event (AE) reports, vital signs and nasal examination 
• 
Change from Visit 1 (Day 1/Baseline) to each time point in subject symptoms and functioning, as 
measured by Sinonasal Outcome Test - 22 (SNOT-22) 
• 
Change in the sense of smell as measured by Sniffin’ Sticks n-butanol (Extended test) 
• 
Patient’s global impression of change (PGIC) 
• 
Percentage of subjects with polyp grade of 0 on at least one side of the nose at each timepoint 
• 
Percentage of subjects with a change of ≥1 point in bilateral polyp grade at each timepoint 
STUDY DESIGN:  This is a 24-week, open-label, multi-center study designed to assess the efficacy and safety 
of OPN-375 186 μg BID in subjects with nasal polyps using Nasoendoscopic Video.  
STUDY POPULATION: The total planned number of subjects is approximately 10. Each subject receives 
OPN-375 186 µg BID. 
DIAGNOSIS AND MAIN CRITERIA FOR ENROLLMENT:  
Potential subjects must meet the following criteria to enter this study: 
1. Men or women aged 18 years and older at Visit 1 (Baseline/Day1) 
2. Women of child bearing potential must be abstinent, or if sexually active,  
a. 
be practicing an effective method of birth control (e.g., prescription oral contraceptives, 
contraceptive injections, contraceptive patch, intrauterine device, double-barrier method [e.g., 
condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], or male partner 
sterilization) before entry and throughout the study, or 
b. be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or 
otherwise be incapable of pregnancy), or 
c. 
be postmenopausal (amenorrhea for at least 1 year).  
3. Women of child-bearing potential must have a negative urine pregnancy test at Visit 1 (Day 
1/Baseline)  
4. Must have bilateral nasal polyposis with a grade of 2 or 3 in at least one side of the nasal cavity as 
determined by a nasal polyp grading scale score measured by nasoendoscopy (see Section 12, 
Efficacy Assessments) at Visit 1 (Day 1/Baseline)   
5. Must have a SNOT-22 score of ≥20 at Visit 1(Baseline/Day 1) (as defined in Section 12, Efficacy 
Assessments)   


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6. Must have been on an adequate dose of an intranasal corticosteroid (e.g. fluticasone propionate, 
fluticasone furoate, mometasone, triamcinolone, ciclosenide, budesonide, budesonide respules, 
beclomethasone) for at least 1 month, in the previous 3 months prior to Visit 1 (Day 1/Baseline)  
7. Subjects with comorbid asthma or chronic obstructive pulmonary disease (COPD) must be stable 
with no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral 
steroid use) within the 3 months before the screening visit. Inhaled corticosteroid use must be 
limited to stable doses of no more than 1,000 μg/day of beclomethasone (or equivalent) for at 
least 3 months before screening with plans to continue use throughout the study 
8. Must be able to cease treatment with oral steroids, intranasal steroids, inhaled corticosteroids 
(except permitted doses listed above for asthma and COPD) at Visit 1 (Day 1/Baseline) 
9. Must demonstrate correct use of the demo EDS 
10. Ability to read and speak English 
11. Must be capable, in the opinion of the investigator, of providing informed consent to participate in 
the study. Subjects must sign an informed consent document indicating that they understand the 
purpose of and procedures required for the study and are willing to participate in the study 
The key exclusion criteria are:  
1. Women who are pregnant or lactating 
2. Inability to have each nasal cavity examined for any reason, including nasal septum deviation 
3. Have used XHANCETM (fluticasone propionate) nasal spray within the past 2 months  
4. Nasal septum perforation 
5. Has had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Day 
1/Baseline)  
6. Have evidence of significant mucosal injury or ulceration (e.g. exposed cartilage) on Visit 1 (Day 
1/Baseline) nasal examination/nasoendoscopy 
7. History of sinus or nasal surgery within 3 months before Visit 1 (Day 1/Baseline).  If >3 months 
subject should be fully recovered from surgery  
8. Current, ongoing rhinitis medicamentosa (rebound rhinitis) 
9. Have significant oral structural abnormalities, e.g., a cleft palate 
10. Diagnosis of cystic fibrosis 
11. History of Churg–Strauss syndrome or dyskinetic ciliary syndromes 
12. Purulent nasal infection, acute sinusitis, or upper respiratory tract infection within 2 weeks before 
Visit 1 (Day 1/Baseline). Potential subjects presenting with any of these infections may be 
rescreened 4 weeks after symptom resolution 
 
13. Planned sinonasal surgery during the period of the study 
14. Allergy, hypersensitivity, or contraindication to corticosteroids, steroids, or to any excipients in 
OPN-375 
15. Exposure to any glucocorticoid treatment with potential for systemic effects (e.g., oral, parenteral, 
intra-articular, or epidural steroids, high dose topical steroids) within 1 month before Visit 1 (Day 
1/Baseline); except as noted in inclusion criteria for subjects with comorbid asthma or COPD 
16. Have nasal candidiasis at Visit 1 (Day 1/Baseline) 
17. History or current diagnosis of any form of glaucoma, ocular hypertension, or intraocular pressure 
elevation on any form of steroid therapy 
18. History or current diagnosis of the presence (in either eye) of a sub-capsular cataract 
19. Any serious or unstable concurrent disease, psychiatric disorder, or any significant condition that, 
in the opinion of the investigator could confound the results of the study or could interfere with the 
subject's participation or compliance in the study 


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20.  Recent (within 1 year of Visit 1 (Day 1/Baseline)) history of drug or alcohol abuse, or dependence 
that, in the opinion of the investigator could interfere with the subject's participation or compliance 
in the study 
21. Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Day 1/Baseline)  
22. Employees of the investigator or study center, with direct involvement in the proposed study or 
other studies under the direction of that investigator or study center, as well as family members of 
the employees or the investigator 
INVESTIGATIONAL PRODUCT, DOSE AND MODE OF ADMINISTRATION: 
Subjects will be instructed to administer one spray of OPN-375 per nostril approximately every 12 hours.  The 
active treatment will contain a formulation of fluticasone propionate that delivers 93 µg per spray.  
REFERENCE THERAPY, DOSE, AND METHOD OF ADMINISTRATION 
N/A – Open Label 
ASSESSMENTS:  
Efficacy:  
The nasal examination and nasoendoscopy with video capture, should be performed by the same physician on 
each subject. If there are multiple physicians performing these assessments, the same physician should perform 
these procedures for the same subject throughout the study. 
The following efficacy evaluations will be performed at the time points specified in Schedule of Study 
Procedures and Evaluations:  
• 
Nasoendoscopy will be performed using a rigid endoscope and the exam will be captured on 
video.  The size and type of scope used in an individual subject should remain consistent 
throughout the study. The examiner must be able to visualize the middle meatus with the scope. 
Decongestants and/or local anesthetics may be used for the nasoendoscopic procedure, however, 
if used at Visit 1 (Day 1/Baseline) in a subject, they must be used consistently at all scheduled 
nasoendoscopic evaluations that follow.  
• 
Polyp grading determined by a nasal polyp grading scale score measured by nasoendoscopy. The 
baseline assessment of polyp grading is performed at Visit 1 (Day 1/Baseline) by the examining 
physician to determine study eligibility. Assessment of polyp grade will be performed by an 
independent reviewer using the videos from the examination.  Subjects and visits will be de-
identified for this review.   
• 
SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional 
consequences of their nasal disorder. Each item is rated as follows: 0=no problem, 1=very mild 
problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as 
it can be. The recall period is the past 2 weeks. The SNOT-22 is validated in chronic 
rhinosinusitis. The SNOT-22 takes approximately 5 minutes to complete. 
• 
The Sniffin’ Sticks n-butanol (Extended test) are used to investigate human olfactory performance 
by use of odor pens.  The Extended Test consists of 3 different subtests: Threshold, 
Discrimination and Identification. The Threshold test is used to ascertain the patient’s olfactory 
threshold.  The Discrimination test requires the patient to differentiate smells.  The Identification 
Test requires the patient to identify everyday smells by means of a card with different choices. 
The test will take approximately 30-40 minutes. All substances contained in the test are non-toxic 
and not harmful in the used concentrations. The result of this test is expressed as the sum of the 
results of the 3 subtests, the so called TDI score (threshold, discrimination, identification). Here a 
score of more than 30 rates as normal, a score of 30 or less indicates hyposmia and a score of 15 
and below points to functional anosmia in form of a complete loss of the sense of smell or an 
extremely weakened smell ability. 


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• 
Subject global impression of change will be assessed using a subject-completed PGIC scale, with 
a single question rated from 1=very much improved to 7=very much worse. The PGIC takes less 
than 1 minute to complete. 
Safety: Safety will be assessed by monitoring of AEs throughout the study, nasal examinations and measuring 
vital signs (i.e., blood pressure, pulse), and through collection of information for concomitant medications 
ENDPOINTS: 
Primary:  
• 
Change from Visit 1 (Day 1/Baseline) at end of study in bilateral nasal polyp grade 
Secondary: 
• 
Assessment of safety through adverse events (AEs) and AEs of special interest (e.g., epistaxis, nasal 
septal ulceration, etc.), nasal examinations, vital signs, and concomitant medication usage 
• 
Change from Visit 1 (Day 1/Baseline) to each visit in bilateral polyp grade 
• 
Number of subjects with a change of ≥1 point in bilateral polyp grade at each visit 
• 
Number of subjects with a polyp grade of 0 on at least one side of the nose at each visit 
• 
Change from Visit 1 (Day 1/Baseline) to each visit in average SNOT-22 score 
• 
Average score on the Sniffin Sticks n-butanol (Extended Test) -  Threshold test, Discrimination test, 
and Identification test at Visit 1 (Day 1/Baseline) and Visit 3 (Week 24/End of Study/Early 
Termination) 
• 
PGIC score at each visit 
DURATION OF THE STUDY:  
The duration of each subject’s enrollment is expected to be approximately 24 weeks. 
Open-Label Treatment Phase:  24 weeks 
STATISTICAL ANALYSIS:  
Sample Size Determination 
No statistical sample size calculation was performed for this study. An empiric sample size of 10 subjects is 
considered to be adequate to assess changes in polyp size and mucosal edema as assessed by nasoendoscopic 
video, as well as for symptomatic endpoints. 
Efficacy Analysis:  
Nasal polyp grade score, SNOT-22 (item and total), Sniffin’ Sticks n-butanol (Extended test) TDI scores, and 
PCIG for each timepoint will be listed for each subject.   
Safety Analysis: 
All reported AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 13.1 
or higher. All AEs during the study period for each subject will be listed and the listing will include the verbatim 
term, System Organ Class [SOC], preferred term, AE start date, AE end date, severity, serious categorization, 
causality, action taken if any, and outcome. 
Vital signs will be listed for each subject. 
Concomitant medications will be coded using the World Health Organization (WHO) Drug Dictionary 
(WHODrug), Version December 2010 or later, and listed by subject.  


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3 
SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS 
Visit(s) 
1 
 
 
2 
 
 
3 
 
Day 1/ 
Baseline 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24 
End of Study / 
Early Termination 
Procedures and assessments 
 
(+/-7 days) 
(+/-7 days) 
(+/-7 days) 
(+/-7 days) 
(+/-7 days) 
(+/-7 days) 
Informed consent 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Prior medication history 
X 
 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
 
 
 
 
 
 
Confirm ability to use demo EDSa 
X 
 
 
 
 
 
 
Urine pregnancy testb 
X 
 
 
X 
 
 
X 
Blood pressure, pulse measurements 
X 
 
 
X 
 
 
X 
SNOT-22 
X 
 
 
X 
 
 
X 
PGIC 
 
 
 
X 
 
 
X 
Sniffin Sticks n-butanol (Extended test) 
X 
 
 
 
 
 
X 
Nasal examinationc 
X 
 
 
X 
 
 
X 
Record polyp grade score from nasal 
polyp grading scalec 
X 
 
 
 
 
 
 
Endoscopic video uploaded 
X 
 
 
X 
 
 
X 
Review proper use of OPN-375 EDS 
X 
 
 
X 
 
 
 
Treatment compliance 
 
X 
X 
X 
X 
X 
X 
Adverse event collectiond 
 
X 
X 
X 
X 
X 
X 
Record concomitant medication 
 
X 
X 
X 
X 
X 
X 
Contact with subjecte 
 
X 
X 
 
X 
X 
 
 
Note:  Screening and Baseline visits are combined.  All visits should be scheduled based on the date of the Visit 1 (Day 1/Baseline). If necessary, visits may be performed 
within the time window shown, however, subsequent visits should be scheduled based on the date of the Visit 1 (Day 1/Baseline). 
a The study staff will dispense a demo EDS (which will be empty) and record in the Accountability Log. This demo EDS is only used at the site at Visit 1 (Day 1/Baseline) 
and subject should not leave the site with the demo EDS. 
b Women of child-bearing potential only; a urine pregnancy test will be performed at the site during each office visit. 
c The nasal examination, nasoendoscopy (including nasal polyp grade), should all be performed by the same physician. If possible, the same physician should perform these 
procedures for the same subject throughout the study. Nasal polyps will be graded by an Independent Reviewer during Visit 2 (Week12) and Visit 3 (Week 24/End of 
Study/Early Termination). 
d The period of observation for collection of adverse events extends from the time the subject gives informed consent until completion of the Visit 3 (Week 24/End of 
Study/Early Termination). Serious adverse events will be reported through 30 days after the last dose of OPN-375 administration.  
e     Subjects will be contacted approximately every 4 weeks between site visits to have information on treatment compliance, adverse events and concomitant medications 
collected 
 


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4 
TABLE OF CONTENTS 
1 
TITLE PAGE ........................................................................................................ 1 
2 
SYNOPSIS ............................................................................................................ 5 
3 
SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS ................ 9 
4 
TABLE OF CONTENTS ................................................................................... 10 
IN-TEXT TABLES .............................................................................................. 13 
IN-TEXT FIGURES ............................................................................................. 13 
5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................. 14 
6 
INTRODUCTION .............................................................................................. 15 
6.1 
Background ...........................................................................................................15 
6.2 
Clinical Experience ...............................................................................................20 
6.3 
Rationale for the Study ..........................................................................................22 
7 
STUDY OBJECTIVES ...................................................................................... 22 
7.1 
Primary Objective ..................................................................................................22 
7.2 
Secondary Objectives ............................................................................................22 
7.3 
Number of subjects and duration of study .............................................................23 
7.4 
Termination of Study .............................................................................................23 
8 
STUDY DESIGN ................................................................................................ 23 
8.1 
Study Overview .....................................................................................................23 
8.2 
Endpoints ...............................................................................................................24 
8.2.1 
Primary Endpoint ...............................................................................24 
8.2.2 
Secondary Endpoints .........................................................................24 
8.3 
Method of Treatment Assignment or Randomization ...........................................25 
9 
SELECTION AND WITHDRAWAL OF SUBJECTS ................................... 25 
9.1 
Inclusion Criteria ...................................................................................................25 
9.2 
Exclusion Criteria ..................................................................................................26 
9.3 
Withdrawal, Removal, and Replacement of Subjects ...........................................28 
9.4 
Follow-Up for Drug Discontinuation/Subject Withdrawal from Study ................28 
10 
STUDY DRUG .................................................................................................... 29 
10.1 
Study Drug Treatment and Dosing ........................................................................29 
10.2 
Clinical Supplies ....................................................................................................30 
10.3 
Packaging and Labeling ........................................................................................30 


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10.4 
Dispensing and Return of Study Drug ..................................................................31 
10.5 
Storage and Reconciliation of Supplies .................................................................31 
10.6 
Concomitant Medication .......................................................................................31 
10.7 
Treatment Compliance ..........................................................................................33 
11 
VISIT SCHEDULE SUMMARY ...................................................................... 33 
11.1 
Visit 1 (Day 1/Baseline) ........................................................................................33 
11.2 
Visit 2 (Week 12) ..................................................................................................34 
11.3 
Visit 3 (Week 24/End-of-Study/Early Termination) .............................................34 
12 
EFFICACY ASSESSMENTS ............................................................................ 34 
13 
SAFETY ASSESSMENTS ................................................................................. 36 
13.1 
Nasal Examination ................................................................................................36 
13.2 
Vital Signs .............................................................................................................37 
13.3 
Laboratory Tests ....................................................................................................37 
13.4 
Adverse Event Definitions and Reporting .............................................................37 
13.4.1 Adverse Events ..................................................................................37 
13.4.2 Adverse Reactions .............................................................................38 
13.4.3 Suspected Adverse Reactions ............................................................39 
13.4.4 Unexpected Adverse Reactions or Adverse Events ...........................39 
13.4.5 Serious Adverse Events .....................................................................40 
13.4.6 Life-Threatening Adverse Events ......................................................40 
13.4.7 Serious Adverse Event Reporting ......................................................41 
13.4.8 Non-Serious Adverse Event Reporting ..............................................41 
13.4.9 Pregnancy ...........................................................................................42 
14 
STATISTICAL ANALYSIS .............................................................................. 42 
14.1 
Sample Size Determination ...................................................................................42 
14.2 
Analysis Datasets ..................................................................................................42 
14.3 
Endpoint Evaluation ..............................................................................................43 
14.4 
Safety Analysis ......................................................................................................43 
14.5 
Interim Analysis ....................................................................................................43 
15 
DATA HANDLING AND RECORD KEEPING ............................................ 43 
15.1 
Case Report Forms ................................................................................................43 
15.2 
Source Documents .................................................................................................44 


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15.3 
Record Retention ...................................................................................................44 
16 
MONITORING .................................................................................................. 44 
17 
QUALITY CONTROL AND QUALITY ASSURANCE ............................... 45 
18 
PROTOCOL AMENDMENT AND PROTOCOL DEVIATION ................. 45 
18.1 
Protocol Amendment .............................................................................................45 
18.2 
Protocol Deviations ...............................................................................................45 
19 
ETHICAL CONSIDERATIONS ...................................................................... 46 
20 
FINANCING AND INSURANCE .................................................................... 46 
21 
PRIVACY OF PERSONAL DATA .................................................................. 46 
22 
PUBLICATION POLICY ................................................................................. 47 
23 
REFERENCES ................................................................................................... 48 
24 
ATTACHMENT 1: BECLOMETASONE – EQUIVALENT DOSES .......... 49 
25 
ATTACHMENT 2: KEY ASSESSMENTS FOR NASAL 
EXAMINATION ................................................................................................ 50 


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IN-TEXT TABLES 
Table 1:  Study Drug Dosing ...................................................................................................29 
Table 2:  Nasal Polyp Grading Scale .......................................................................................35 
Table 3:  Patient Global Impression of Change (PGIC) Scale.................................................36 
Table 4:  Adverse Event Severity ............................................................................................38 
 
IN-TEXT FIGURES 
Figure 1. Closed Palate Bi-directional Delivery Concept ......................................................18 
Figure 2. OPN-375 .................................................................................................................19 
Figure 3:  Study Flow Diagram ...............................................................................................24 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation or Term 
Definition 
AE 
Adverse Event 
 BID 
Two times a day 
CFR 
Code of Federal Regulations 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
DCF 
Data Clarification Form 
EDS 
Exhalation Delivery System 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
 IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
NARES 
Nonallergic Rhinitis with Eosinophilia Syndrome 
NSAID 
Nonsteroidal Anti-inflammatory Drug 
OMC 
Ostiomeatal Complex 
PGIC 
Patient Global Impression of Change 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SNOT-22 
Sinonasal Outcome Test 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
US 
United States 
WHO 
World Health Organization 
WHODrug 
World Health Organization Drug Dictionary 


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6 
INTRODUCTION 
OptiNose is developing OPN-375 (XHANCETM (fluticasone propionate) nasal spray) as an 
intranasal drug delivery system with the intention to improve the performance of fluticasone 
propionate in the treatment of nasal inflammatory diseases by facilitating deposition of the 
topical steroid in regions affected by local inflammation that lead to chronic nasal symptoms 
(e.g., the ostiomeatal complex).  Delivery of drug, using an Exhalation Delivery System (EDS), 
is intended to improve reproducibility of nasal delivery, particularly deposition of the topical 
steroid in the region where many polyps originate (producing physical obstruction and 
inflammatory mediators) and where polyp obstruction threatens normal physiologic ventilation 
and drainage of the paranasal sinuses.  OPN-375 is also intended to address user preference 
associated with reduced drip-out (posterior and anterior) and taste, and to improve tolerability 
and efficiency by significantly reducing loss of drug to nontarget sites such as the 
gastrointestinal (GI) tract and lungs. 
Fluticasone propionate is an androstane glucocorticoid with high lipophilicity, high selectivity 
and affinity for the glucocorticoid receptor, low oral and nasal systemic absorption, and rapid 
metabolic clearance (Crim 2001). It is approved in many countries for use in the treatment of 
dermatosis (topical), rhinitis (intranasal), and asthma and chronic obstructive pulmonary 
disease (COPD) (inhaled), and is one of the most well studied and characterized 
glucocorticoids in clinical use today. 
Information on OPN-375 for treatment of nasal polyposis is summarized in the following 
sections. For the most comprehensive information on the safety and efficacy of OPN-375 refer 
to the most recent version of the Investigator’s Brochure (IB). 
The terms "Sponsor" or “designee” used throughout this document refers to those companies 
or individuals listed on the Contact Information page(s), which will be provided as a separate 
document. 
6.1 
Background 
A clinical development program for OPN-375 (XHANCETM) in adults with nasal polyposis 
has been completed.  XHANCETM is currently approved for the treatment of nasal polyps in 


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patients 18 years of age or older.  OptiNose is intending to gather additional information on 
the impact of OPN-375 on the signs and symptoms associated with nasal polyposis.   
Nasal polyps are benign lesions arising from the mucosa of the nasal sinuses or from the 
mucosa of the nasal cavity. The clinical symptoms associated with nasal polyposis often 
depends on the size and location of the polyp. Small nasal polyps are generally asymptomatic 
but when located in areas such as the middle meatus, they may produce symptoms. Patients 
with multiple and/or larger polyps may suffer partial or complete obstruction of the nasal 
passages and/or sinus ostia, which may result in chronic or recurrent acute sinusitis symptoms.  
Thus, signs and symptoms of nasal polyps may include rhinorrhea, persistent stuffiness, post-
nasal drip, decreased or absent sense of smell, loss of taste, facial pain, or headache (Meltzer 
2004, Fokkens 2012). Anterior polyps may be visualized on nasal examination or rhinoscopy 
with an otoscope.  Nasoendoscopy is usually required to visualize posterior polyps.     
The development of nasal polyps has been associated with chronic inflammation, autonomic 
nervous system dysfunction and genetic predisposition.  Nasal polyps have been associated 
with allergic rhinitis, asthma, chronic rhinosinusitis, allergic fungal sinusitis; genetic diseases 
such as cystic fibrosis, primary ciliary dyskinesia, and Young syndrome; clinical syndromes 
such as Churg-Strauss syndrome, and other hypereosinophilic conditions such as aspirin or 
alcohol intolerance and nonallergic rhinitis with eosinophilia syndrome (NARES) (Chaaban 
2013).   
The prevalence of nasal polyps has been estimated to be 1-4%.  Nasal polyps can be removed 
surgically or treated with steroid medication, given orally, by intrapolyp injection, or topically 
by nasal sprays or drops. None of these methods have proven entirely curative and people often 
require multiple surgical procedures. Oral steroids may reduce the need for surgery but there 
are concerns about significant side effects with long-term oral steroid use. Among the 
intranasal glucocorticoids available in the U.S., beclomethasone (Beconase AQ®) has been 
approved for prophylaxis of nasal polyps post-surgical resection, and mometasone (Nasonex®) 
and fluticasone (XHANCETM) have been approved for the treatment of nasal polyps; both of 
these indications are only in adults (Prescribing Information for Beconase AQ [2005] and 
Nasonex [2013], and XHANCETM [2017]).   


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OPN-375 
OPN-375 contains a liquid suspension of fluticasone propionate that it delivers to the nasal 
mucosa with a drug delivery system designed to deposit the drug aerosol high and deep into 
the nasal cavity.  Fluticasone propionate is a synthetic corticosteroid that has long been 
commercially available in the US.  It is currently approved as monotherapy and in various 
combinations, and in multiple formulations for multiple indications including creams (for 
inflammatory dermatoses and other dermatological conditions), inhalers (for asthma and other 
respiratory conditions), and nasal sprays (for rhinitis and nasal polyposis). 
OPN-375 delivers active medication using an EDS.  It is composed of a pharmaceutical 
industry standard amber glass vial containing a suspension of fluticasone propionate, a 
standard metering spray pump, and plastic casework with an asymmetrically shaped sealing 
nosepiece and a flexible mouthpiece.  The casework defines the drug delivery system’s outer 
shape and includes the moveable mouthpiece and sealing nosepiece.  The user inserts the 
sealing nosepiece into one nostril, so it seals well with the flexible nasal tissues, and inserts the 
mouthpiece between the lips.  After taking a deep breath, the user closes the lips around the 
mouthpiece and blows into the OPN-375 mouthpiece.  Static positive pressure is created and 
subsequently released through the actuation of the spray by pressing the vial, which 
concurrently releases the orally-generated pressure/airflow.  Blowing through the mouth 
against a resistance also causes the soft palate to seal closed, separating the oral cavity from 
the nasal cavities.  A nasal spray applicator extends from the metering pump to the tip of the 
nosepiece.  Upon actuation, the design of the EDS allows for air to be channeled from the 
mouthpiece to the sealing nosepiece when the pump is actuated.  Under these conditions, 
exhaled air creates a positive intranasal pressure, accompanies the aerosol expelled by the 
spray pump applicator beyond the nasal valve, and places at least 50% of the initially deposited 
metered spray beyond the head of the inferior turbinate and at least 30% of the initially 
deposited dose in the upper posterior region of the nasal cavity beyond the head of the inferior 
turbinate and above the inferior meatus, including the ostiomeatal complex (OMC) (middle 
meatus).  This pattern of delivery produced by OPN-375 is intended to place topical steroid in 
the region of the nasal cavity where many polyps originate (producing physical obstruction 
and releasing inflammatory mediators), and where polyp obstruction threatens normal 


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physiologic ventilation and drainage of the paranasal sinuses.  OPN-375 EDS is also intended 
to address user preference associated with reduced drip-out (posterior and anterior) and taste, 
and to improve tolerability and efficiency by significantly reducing loss of drug to non-target 
sites inside the body such as the gastrointestinal tract and lungs. 
Figure 1 presents a schematic view of closed palate Breath Powered™ Bi-Directional™ 
delivery and an image of OPN-375. 
Figure 1. 
Closed Palate Bi-directional Delivery Concept 
 
Schematic A 
 
Schematic B 
 
 
Closed palate bi-directional Delivery Concept 
 
A = Cross-sectional view from the left side. 
 
B = Cross-sectional view from the top. 
 
 
The EDS has a flexible mouthpiece and a sealing nosepiece. The nosepiece is shaped to transfer 
pressure from the mouth, avoid obstruction by compression of soft tissue, and expand the upper 
part of the nasal valve.  Exhalation through the EDS: 1) creates an airtight seal of the soft-
palate, isolating the nose from the mouth and lungs, 2) transfers proportional pressure into the 
nose, and 3) helps “float” medication around obstructions to deposit in high/deep sites in the 
nasal labyrinth, such as the OMC.  The transferred pressure is proportional to varying 


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exhalation force, counterbalanced by the pressure on the soft palate. This assures a patent 
communication behind the nasal septum, allowing air to escape through the opposite nostril. 
“Positive-pressure” expands passages narrowed by inflammation (versus negative pressure 
delivery, “sniffing”). 
Use is simple and quick. A patient inserts the nosepiece into one nostril and starts blowing 
through the mouthpiece. This elevates and seals the soft palate, as with inflating a balloon, 
separating the oral and nasal cavities. The patient completes use by pressing the bottle to 
actuate.  This causes a coordination-reducing valve to release the exhaled breath concurrently 
with aerosol spray in a “burst” of naturally humidified air. 
OPN-375 is shown pictorially in Figure 2.  
Figure 2. 
OPN-375 
 
Before OPN-375 is used for the first time, it is necessary to prime the unit. To prime the unit, 
shake, then actuate and spray into the air 7 times or until a fine mist appears. 
 


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6.2 
Clinical Experience 
XHANCE™ (fluticasone propionate) nasal spray was approved in September 2017 on the 
basis of a clinical program demonstrating safety and efficacy. There were two Phase 3, 
randomized, double-blind, placebo-controlled, parallel-group, multicenter studies (OPN-
FLU-NP-3101 and OPN-FLU-NP-3102) conducted to assess the efficacy and safety of 3 
doses of OPN-375 (93, 186, and 372 μg BID) compared with placebo in adult subjects with 
bilateral nasal polyposis followed by an 8-week open-label extension phase (372 μg BID) to 
assess safety. The clinical studies were identical in design. 
In these studies, all three OPN-375 doses produced statistically significant greater reductions 
than placebo on the co-primary measures of nasal congestion/obstruction and total polyp 
grade.  Sensitivity analyses conducted on the co-primary outcome variables, including a 
tipping point analysis, indicated that the results obtained were robust.  Results from the co-
primary analyses conducted with the integrated data were consistent with the results of the 
individual pivotal studies.  The 186 µg and 372 µg groups had numerically larger magnitudes 
of effect compared with the 93 µg group.   
Results obtained from secondary measures in the pivotal studies were generally consistent 
with the primary efficacy results.  In the open-label phases of the pivotal trials, the 
improvements from baseline in efficacy assessments seen at the end of the double-blind 
phases generally continued to increase through week 24.  Data from responder analyses 
demonstrate that OPN-375 substantially reduces polyp grade and the magnitude of reduction 
continues to increase with longer-term treatment within the period studied.  
Clinically meaningful improvements with OPN-375 treatment were also observed broadly in 
other signs and symptoms of the disease and in physical and emotional parameters relevant to 
quality of life.  Analyses of the Patient Global Impression of Change (PGIC) indicated that 
treatment with OPN-375 not only produced statistically significant benefits but that the 
magnitude of change perceived by the subject was clinically meaningful. 


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There were two Phase 3, open-label, multicenter studies (OPN-FLU-CS-3203, 12-month; 
OPN-FLU-CS-3204, 3-month) designed to assess the safety and efficacy of OPN-375 372 μg 
BID in subjects with or without nasal polyps. 
Subjects in the open-label studies also had considerable improvement in symptoms and in 
objectively observed local signs of disease.  A substantial proportion of subjects with 
intranasal edema at study entry no longer had evidence of edema on examination at study 
completion, a finding consistent with an intranasal deposition profile that places topically-
acting fluticasone propionate in the areas beyond the nasal valve including the area of the 
middle meatus/ostiomeatal complex.  In subjects with polyps, extensive reductions in polyp 
grade were observed and polyps were eliminated from at least 1 side of the nose in 
approximately 50%.  In the 12-month study the improvement in polyp grade increased over 
time, suggesting benefit with continued treatment over the observed period.   
Safety  
The most commonly reported adverse events (AEs) in the active treatment groups were 
associated with local effects at the site of administration in the nasal cavity (epistaxis, nasal 
congestion, nasal mucosal disorder [primarily erythema], and nasal septum ulceration) or 
associated with the underlying disease (acute sinusitis or nasopharyngitis).  Most local AEs 
were identified as a result of intensive active monitoring of all subjects at scheduled intervals 
by skilled nasoendoscopic examination at each visit and were not spontaneously reported.  
The majority of these AEs were mild and importantly, are known to have resolved with 
continued use of study drug.  No deaths were reported, 18 subjects receiving OPN-375 
reported serious adverse events (SAEs) during the placebo controlled and open-label studies.  
One placebo-treated subject reported a treatment-related SAE, and the overall rate of 
discontinuations due to AEs was approximately 4% among all subjects who received OPN-
375. 
Epistaxis was the most common AE reported in clinical trials.  The AEs coded to epistaxis 
were either spontaneously reported clinical events or were observations of mucosal bleeding 
(active or nonactive bleeding) made during a nasoendoscopic examination.  The epistaxis 
coded AEs were primarily mild, and most were observed on the nasal endoscopic 


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examination rather than being captured in a spontaneous report by the subject.  The majority 
of bleeding events identified via nasal examination were categorized as nonactive (evidence 
of clots or previous bleeding).  Over 90% of AEs coded to epistaxis in these studies resolved 
with continued use of study drug.  The incidence of epistaxis appeared to have been highest 
in the first months of study participation when nasal examinations were more frequent.  
6.3 
Rationale for the Study 
Current nasal steroid treatments are suboptimal in reliably reaching target sites beyond the 
nasal valve (Aggarwal 2004). In order to reduce inflammation and polyp size the drug must 
reach the polyps in sufficient quantities. The EDS, with its unique mechanism of delivery, 
provides specific benefits over current nasal drug delivery systems including increased 
reliability of delivery of topical medication to the anatomical sites which are central to the 
pathology of nasal polyps. 
The results from phase 3 clinical studies in adults with nasal polyposis have demonstrated that 
OPN-375 is both safe and effective.  This study is being conducted to provide nasoendoscopic 
video evidence of the changes that occur with OPN-375 treatment.     
7 
STUDY OBJECTIVES 
7.1 
Primary Objective 
The primary objective of this study is to document the changes in polyp burden over time using 
nasoendoscopic video.  
7.2 
Secondary Objectives 
Secondary objectives of this study include: 
• Evaluate the safety of OPN-375 via adverse event (AE) reports, vital signs and nasal 
examination 
• Change from baseline to each time point in subject symptoms and functioning, as 
measured by Sinonasal Outcome Test - 22 (SNOT-22) 
• Change in the sense of smell as measured by Sniffin’ Sticks n-butanol (Extended test) 
• Patient’s global impression of change (PGIC) 


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• Percentage of subjects with polyp grade of 0 on at least one side of the nose at each 
timepoint 
• Percentage of subjects with a change of ≥1 point in bilateral polyp grade at each 
timepoint 
7.3 
Number of subjects and duration of study 
The total planned number of subjects is approximately 10. Each subject will receive OPN-375 
186 µg BID. 
The expected participation period for a subject is approximately 24 weeks.  
7.4 
Termination of Study 
Premature termination of the trial may occur because of a regulatory authority decision, change 
in opinion of the Institutional Review Board (IRB), drug safety problems, or at the discretion 
of the Sponsor or their designee. If the study is prematurely terminated, the Sponsor or their 
designee will promptly notify the investigators. 
8 
STUDY DESIGN  
8.1 
Study Overview 
This is an open-label, multi-center study designed to assess the efficacy and safety of OPN-
375 186 μg BID delivered in subjects with nasal polyps. Approximately 10 subjects will be 
enrolled. 
This study consists of 24 Weeks of open-label treatment. All visit procedures will be performed 
at the time points indicated on the Time and Events Schedule. 
Subjects will undergo screening during the Visit 1 (Day 1/Baseline) visit to determine study 
eligibility.  
Subjects who continue to meet eligibility criteria at Visit 1 (Day 1/Baseline) will be instructed 
on the use of OPN-375, including dosing instructions, and will receive a 3-month supply of 
OPN-375. 
During the 24 Week open-label treatment, subjects will return to the study site at Visit 2 (Week 
12), and then Visit 3 (Week 24/End of Study/Early Termination) for efficacy and safety 


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evaluations. At each visit nasoendoscopy will be performed with the examination being 
captured on video.  The investigator will complete the nasal examination.  The investigator 
will utilize appropriate video capturing equipment and will follow the standardized procedure 
outlined in the nasal examination procedure document.   
Subjects will be contacted approximately every 4 weeks between site visits to have information 
on treatment compliance, adverse events and concomitant medications collected.  
At Visit 3 (Week 24/End of Study/Early Termination), or if a subject discontinues study drug 
before the end of study, an end of study/early termination visit should be performed. 
 
A study flow diagram is shown in Figure 3.  
Figure 3:  Study Flow Diagram 
 
 
Open-Label Treatment 
 
 
 
 
 
186 g OPN-375 BID    
 
 
(N=10) 
 
 
 
Visit 
Visit 1 
Day 1/ 
Baseline 
 
 
Visit 2 
Week 12 
 
Visit 3 
Week 24/ 
End of Study/ 
Early Termination 
Subject Contact 
 
Week 4,8 
 
Week 16,20 
 
 
8.2 
Endpoints 
8.2.1 Primary Endpoint 
Primary Endpoint 
• Change from Visit 1 (Day 1/Baseline) at end of study in bilateral nasal polyp grading 
using nasoendoscopic video 
8.2.2  Secondary Endpoints 
Secondary Endpoint 


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• Assessment of safety through adverse events (AEs) and AEs of special interest (e.g., 
epistaxis, septal ulceration, etc.), nasal examinations, vital signs, and concomitant 
medication usage 
• Change from Visit 1 (Day 1/Baseline) to each visit in bilateral polyp grade 
• Number of subjects with a change of ≥1 point in bilateral polyp grade at each visit 
• Number of subjects with a polyp grade of 0 on at least one side of the nose at each visit 
• Change from Visit 1 (Day 1/Baseline) to each visit in average SNOT-22 score 
• Average score on the Sniffin’ Sticks n-butanol (Extended test) - Threshold test, 
Discrimination test, and Identification at Visit 1 (Day 1/Baseline) and Visit 3 (Week 
24/End of Study/Early Termination). 
• PGIC score at each visit 
 
8.3 
Method of Treatment Assignment or Randomization 
Following completion of all Visit 1 (Day 1/Baseline) evaluations, subjects who meet all 
eligibility requirements will be provided with OPN-375 186 μg BID. 
9 
SELECTION AND WITHDRAWAL OF SUBJECTS 
9.1 
Inclusion Criteria 
Potential subjects must meet the following criteria to enter this study: 
1. Men or women aged 18 years and older at Visit 1 (Day 1/Baseline) visit 
2. Women of child bearing potential must be abstinent, or if sexually active,  
a. be practicing an effective method of birth control (e.g., prescription oral 
contraceptives, contraceptive injections, contraceptive patch, intrauterine 
device, double-barrier method [e.g., condoms, diaphragm, or cervical cap 
with spermicidal foam, cream, or gel], or male partner sterilization) before 
entry and throughout the study, or 
b. be surgically sterile (have had a hysterectomy or bilateral oophorectomy, 
tubal ligation, or otherwise be incapable of pregnancy), or 
c. be postmenopausal (amenorrhea for at least 1 year).  
3. Women of child-bearing potential must have a negative urine pregnancy test at the 
baseline visit  


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4. Must have bilateral nasal polyposis with a grade of 2 or 3 in at least one side of the 
nasal cavity as determined by a nasal polyp grading scale score measured by 
nasoendoscopy (see Section 12, Efficacy Assessments) at Visit 1 (Day 1/Baseline)   
5. Must have a SNOT-22 score of ≥20 at Visit 1(Baseline/Day 1) (as defined in Section 
12, Efficacy Assessments)   
6. Must have been on an adequate dose of an intranasal corticosteroid (e.g. fluticasone 
propionate, fluticasone furoate, mometasone, triamcinolone, ciclosenide, budesonide, 
budesonide respules, beclomethasone) for at least 1 month, in the previous 3 months 
prior to Visit 1 (Day 1/Baseline)  
7. Subjects with comorbid asthma or chronic obstructive pulmonary disease (COPD) 
must be stable with no exacerbations (e.g., no emergency room visits, hospitalization, 
or oral or parenteral steroid use) within the 3 months before the screening visit. 
Inhaled corticosteroid use must be limited to stable doses of no more than 1,000 
μg/day of beclomethasone (or equivalent) for at least 3 months before screening with 
plans to continue use throughout the study  
8. Must be able to cease treatment with oral steroids, intranasal steroids, inhaled 
corticosteroids (except permitted doses listed above for asthma and COPD) at Visit 1 
(Day 1/Baseline). 
9. Must demonstrate correct use of the demo EDS  
10. Ability to read and speak English 
11. Must be capable, in the opinion of the investigator, of providing informed consent to 
participate in the study. Subjects must sign an informed consent document indicating 
that they understand the purpose of and procedures required for the study and are 
willing to participate in the study. 
9.2 
Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from entering this 
study: 
1. Women who are pregnant or lactating 
2. Inability to have each nasal cavity examined for any reason, including nasal septum 
deviation 
3. Have used XHANCE™ (fluticasone propionate) nasal spray within the past 2 
months  
4. Nasal septum perforation 
5. Has had more than 1 episode of epistaxis with frank bleeding in the month before 
Visit 1 (Day 1/Baseline)  
6. Have evidence of significant mucosal injury or ulceration (e.g. exposed cartilage) 
on Visit 1 (Day 1/Baseline) nasal examination/nasoendoscopy 


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7. History of sinus or nasal surgery within 3 months before Visit 1 (Day 1/Baseline).  
If >3 months subject should be fully recovered from surgery  
8. Current, ongoing rhinitis medicamentosa (rebound rhinitis) 
9. Have significant oral structural abnormalities, e.g., a cleft palate 
10. Diagnosis of cystic fibrosis 
11. History of Churg–Strauss syndrome or dyskinetic ciliary syndromes 
12. Purulent nasal infection, acute sinusitis, or upper respiratory tract infection within 
2 weeks before Visit 1 (Day 1/Baseline). Potential subjects presenting with any of 
these infections may be rescreened 4 weeks after symptom resolution  
13. Planned sinonasal surgery during the period of the study 
14. Allergy, hypersensitivity, or contraindication to corticosteroids, or to any excipients 
in OPN-375 
15. Exposure to any glucocorticoid treatment with potential for systemic effects 
(e.g., oral, parenteral, intra-articular, or epidural steroids, high dose topical 
steroids) within 1 month before Visit 1 (Day 1/Baseline); except as noted in 
inclusion criteria for subjects with comorbid asthma or COPD 
16. Have nasal candidiasis at Visit 1 (Day 1/Baseline) 
17. History or current diagnosis of any form of glaucoma, ocular hypertension, or 
intraocular pressure elevation on any form of steroid therapy 
18. History or current diagnosis of the presence (in either eye) of a sub-capsular cataract 
19. Any serious or unstable concurrent disease, psychiatric disorder, or any significant 
condition that, in the opinion of the investigator could confound the results of the 
study or could interfere with the subject's participation or compliance in the study 
20. A recent (within 1 year of Visit 1 (Day 1/Baseline)) history of drug or alcohol abuse, 
or dependence that, in the opinion of the investigator could interfere with the 
subject's participation or compliance in the study 
21. Have participated in an investigational drug clinical trial within 30 days of Visit 1 
(Day 1/Baseline)  
22. Employees of the investigator or study center, with direct involvement in the 
proposed study or other studies under the direction of that investigator or study 
center, as well as family members of the employees or the investigator 


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9.3 
Withdrawal, Removal, and Replacement of Subjects 
Subjects will be informed that they are free to withdraw from the study at any time at their own 
request without prejudice to their future medical care, or that they may be withdrawn at any 
time at the discretion of the investigator or Sponsor for safety, non-adherence to protocol 
requirements, or administrative reasons (e.g., termination of study by Sponsor).  
A subject must be withdrawn for the following reasons: 
• Withdrawal of consent 
• The subject becomes pregnant 
• Discontinuation of study treatment. A subject’s study treatment will be 
discontinued if the investigator or Sponsor considers it in the subject’s best interest 
to stop treatment, (e.g., for safety or significant tolerability reasons such as an AE) 
• Termination of the study 
A subject may also be withdrawn for the following reasons: 
• Lost to follow-up 
• Lack of efficacy 
• Protocol violation 
If a subject withdraws from the study after starting study treatment, appropriate follow-up must 
be conducted wherever possible. 
9.4 
Follow-Up for Drug Discontinuation/Subject Withdrawal from Study 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, every effort should be made to document the subject’s outcome, 
if possible. The investigator should inquire about the reason for withdrawal, request the return 
of all investigational product, and request the subject return for a final study visit and 
examination. 
The date and the reason for subject withdrawal from the study must be recorded on the Case 
Report Form (CRF).   


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10 
STUDY DRUG 
10.1 Study Drug Treatment and Dosing 
As shown in Table 1, the study drug dosage will be 186 μg  OPN-375 BID.  Each spray delivers 
93 μg of fluticasone propionate per actuation.  
Table 1:  Study Drug Dosing 
Dosage 
Times of administration 
186 μg BID 
1 spray each nostril every morning 93 μg per spray  
1 spray each nostril every evening 93 μg per spray  
 
During this open-label treatment study, all subjects will receive 186 μg of fluticasone 
propionate BID, and the same dosing procedure will be followed for both the AM and PM 
doses on each day. The study staff will instruct the subject to shake OPN-375 before use, and 
then administer 1 spray to the right nostril and 1 spray to the left nostril.  
At Visit 1 (Day 1/Baseline), subjects will be provided with a demo EDS to practice 
administration of a dose and to assure that they can correctly use the EDS (e.g., able to obtain 
a seal, aim the EDS appropriately, correctly sequence steps). The study staff will record in the 
accountability log. This demo EDS is only to be used at the site at Visit 1 (Day 1/Baseline) and 
subject should not leave the site with the demo EDS. 
Open-label study drug will be dispensed to subjects at Visit 1 (Day 1/Baseline) and at Visit 2 
(Week 12): 
• Visit 1 (Day 1/Baseline): 3 kits (Each kit contains 1 bottle) 
• Visit 2 (Week 12): 3 kits (Each kit contains 1 bottle)   
Throughout the study, subjects will be instructed to shake OPN-375 before use. They will also 
be instructed that it is only necessary to prime OPN-375 before it is used for the first time as 
follows:  


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• To prime OPN-375, shake, then actuate and spray into the air 7 times or until a fine 
mist appears. Note that it is not necessary to prime OPN-375 before every 
administration when OPN-375 is being used regularly each day.  
The first dose of study drug should be administered in the evening (PM) on Day 1. Throughout 
the study, subjects will be instructed to administer study drug approximately every 12 hours. 
If a subject misses a dose, the dose should be taken as soon as remembered, but not within 
2 hours of the next scheduled dose. In such cases the subject should wait until the next 
scheduled dosing time to administer a dose. 
The study staff will instruct subjects to report OPN-375 they perceive to be broken or 
malfunctioning and to return any such OPN-375 to the study site for evaluation and 
identification of the problem. Study staff will return the malfunctioning OPN-375 to the 
Sponsor for evaluation and identification of the issue. 
An instruction sheet on the use of OPN-375 will be provided by the Sponsor or their designee 
to be given to the subjects. 
10.2 Clinical Supplies 
The fluticasone propionate formulation is a milky, white suspension contained in an amber 
glass bottle crimp sealed by the nasal spray pump. Each actuation delivers 93 µg of fluticasone 
propionate through the nasal sealing nozzle. The number of deliveries per OPN-375 (after 
priming) is not less than 120. 
10.3 Packaging and Labeling 
The demo EDS is only to be used only at Visit 1 (Day 1/Baseline) to confirm subject’s ability 
to use the EDS.  The demo EDS will be packaged containing one demo EDS. 
Open-label study drug will be packaged in a kit and will consist of one OPN-375 containing 
93 μg per spray of study drug.  
Labeling will contain all information required by local regulations. 


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10.4 Dispensing and Return of Study Drug 
The investigator or designee at each site will maintain accurate records of open-label OPN-
375 and demo EDS units received, including to whom study drug has been dispensed, dates 
and quantity. All demo and OPN-375 units should be returned to storage, and accounted for, 
including dates and quantity (subject by subject accounting).  Any open-label OPN-375 or 
demo EDS accidentally or deliberately destroyed will also be documented. 
10.5 Storage and Reconciliation of Supplies 
All study drug will be supplied by the Sponsor and should be stored securely in a locked 
facility. 
All study drug must be stored at room temperature (between 15°C and 25°C: 59°F and 77°F, 
with excursions permitted from 15°C and 30°C: 59°F and 86°F). Avoid exposure to extreme 
heat, cold or light.  Shake OPN-375 before each use. Keep all study drug in the manufacturer’s 
packaging. 
The shelf life of the product will be supported by ongoing stability studies.  
All used and unused OPN-375 will be returned to the Sponsor or designee at the end of the 
study. Reasons for departure from the expected dispensing or return of OPN-375 must be 
recorded. 
10.6 Concomitant Medication 
All pre-study medications used within 1 month before Visit 1 (Day 1/Baseline) must be 
recorded in the CRF. For subjects with comorbid asthma or COPD, pre-study inhaled steroid 
(beclomethasone or equivalent) use within the 3 months before Visit 1 (Day 1/Baseline) must 
be recorded in the CRF.  
Concomitant medications include all medications and other treatments taken by the subject 
during the study, including those treatments initiated prior to the start of the study. All 
concomitant medications must be recorded on the CRF. 


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Allowed Concomitant Medications 
In subjects with comorbid asthma at study entry (i.e., Visit 1 (Day 1/Baseline)), inhaled 
corticosteroid use must be limited to stable doses of no more than 1,000 μg/day of 
beclomethasone HFA (or equivalent; see Attachment 1). Subjects must be on a stable dose for 
at least 1 month before Visit 1 (Day 1/Baseline) with plans to continue use throughout the 
study.  
Other concomitant medications allowed include: 
• Antibiotic medications will be permitted for bacterial infections that develop during the 
study. 
• Intranasal saline spray may be used with the exception of use within 2 hours before or 
after study drug administration.     
• Saline lavage will be permitted only for those subjects regularly using it before study 
entry; subjects may not initiate use during the study. Saline lavage must not be 
performed within 2 hours before or after study drug administration. 
• Intranasal antibiotics are permitted, but must not be given without 2 hours before or 
after study drug administration. 
• Stable doses (within 2 weeks of the Visit 1 (Day 1/Baseline)) of leukotriene receptor 
antagonists, beta-blockers, and neuroleptics 
• Low to medium strength topical corticosteroids for dermatologic purposes  
Other concomitant medications are allowed, if not specially listed below as prohibited. 
Prohibited Medications 
• Exposure to any glucocorticoid treatment with potential for systemic effects (e.g., oral 
or parenteral steroids, high dose topical steroids) within 1 month before the screening 
visit through completion of the study; except as noted for subjects with comorbid 
asthma or COPD.    
• Any systemic, inhaled, intranasal and topical corticosteroids (except low to medium 
strength topical corticosteroids as noted above)  
• XHANCETM (fluticasone propionate) nasal spray 
• Nucala (mepolizumab), Cinquair (reslizumab), Dupixent (dupilumab), or 
Omalizumab (Xolair®) 
• Strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, 
clarithromycin, 
indinavir, 
itraconazole, 
nefazodone, 
nelfinavir, 
saquinavir, 
ketoconazole, telithromycin, conivaptan, lopinavir, voriconazole) with OPN-375 is 
prohibited because increased systemic corticosteroid adverse effects may occur. 


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10.7 Treatment Compliance 
At each visit after Visit 1 (Day 1/Baseline), subjects will be instructed to bring their partially 
used/empty OPN-375 units back to the study site at each study visit. At each study visit, all 
subjects will be reminded of the importance of compliance with their assigned regimen with 
an emphasis on correct use of OPN-375 and the administration of and timing of doses. 
11 
VISIT SCHEDULE SUMMARY 
Procedures to be performed at each study visit, and the visit time windows, are indicated in 
Section 3, Schedule of Study Procedures and Evaluations. Additional information related to 
the individual study visits is presented in the subsections that follow. 
The different visits and allowable timing for the nasoendoscopic-related procedures are as 
presented below and in Section 3, Schedule of Study Procedures and Evaluations: 
• The Visit 1 (Day 1/Baseline) nasal examination and nasoendoscopy, are the 
baseline assessments for these procedures.  
• For Visit 2 (Week 12) and Visit 3 (Week 24/End of Study/Early Termination) study 
visits, if the nasal examination and nasoendoscopic assessments cannot be 
performed on the same day as the study visit, they may be performed before or after 
the study visit, but must be performed within the same 7-day window around the 
expected study visit date (i.e., visit date calculated based on Day 1). 
 
11.1 Visit 1 (Day 1/Baseline) 
Subjects will be provided with an informed consent form that will explain the objectives of the 
study and its potential risks and benefits. The subject should have adequate time to read the 
informed consent and to ask the investigator any questions. The investigator must be satisfied 
that the subject has understood the information provided before written consent is obtained. If 
there is any doubt as to whether the subject has understood the written and verbal information, 
the subject should not enter the study. A copy of the signed informed consent form will be 
given to the subject and the original filed in the site file. 
After informed consent has been obtained, subjects will undergo all Visit 1 (Day 1/Baseline) 
procedures indicated in the Schedule of Study Procedures and Evaluations in Section 3, to 
determine study eligibility. 


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Subjects will be instructed on the use of OPN-375. They will then be provided with a demo 
EDS to practice and to assure that they can correctly use the EDS (e.g., able to obtain a seal 
between the nosepiece and the nostril, sequence). The study staff will dispense a demo EDS 
and record in the accountability log. This demo EDS is only to be used at the site at Visit 1 
(Day 1/Baseline) and subject should not leave the site with the demo EDS. The subject must 
be able to correctly use the demo EDS prior to entering the study. 
Subjects who then meet all eligibility criteria at Visit 1 (Day 1/Baseline), will enter the study 
and receive 186 µg of OPN-375 BID. OPN-375 will be administered as described in 
Section 10.1, Study Drug Treatment and Dosing. Subjects will be given 3 kits (each containing 
1 OPN-375 unit). Subjects will be instructed to bring the OPN-375 unit with them to their next 
visit.  
11.2 Visit 2 (Week 12) 
During the study, subjects will return to the study site at Visit 2 (Week 12), to have efficacy 
evaluations performed and safety assessed as detailed in Section 3, Schedule of Study 
Procedures and Evaluations.  
11.3 Visit 3 (Week 24/End-of-Study/Early Termination)  
Subjects who complete 24-weeks of study treatment, and those who prematurely withdraw 
from the study for any other reason during this phase should return to the study site and have 
the end-of-study/early termination visit performed.  
12 
EFFICACY ASSESSMENTS 
The Schedule of Study Procedures and Evaluations in Section 3 indicates the timing of all 
assessments; further information on each evaluation is provided below.  
The nasal examination and nasoendoscopic video, should be performed by the same physician 
on each subject. If there are multiple physicians performing these assessments, the same 
physician should perform these procedures for the same subject throughout the study. The 
Schedule of Study Procedures and Evaluations in Section 3 and Section 11, Visit Schedule 
Summary, indicates the visits, as well as various visit time windows, at which these 


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assessments will be performed. Additional information on the nasal examination can be found 
in Section 13, Safety Assessments.  
The following efficacy evaluations will be performed at the time points specified in Section 3, 
Schedule of Study Procedures and Evaluations:    
• Nasoendoscopy will be performed using a rigid endoscope and the exam will be 
captured on video.  The size and type of scope used in an individual subject should 
remain consistent throughout the study. The examiner must be able to visualize the 
middle meatus with the scope. Decongestants and/or local anesthetics may be used 
for the nasoendoscopic procedure, however, if used at Visit 1 (Day 1/Baseline) in 
a subject, they must be used consistently at all scheduled nasoendoscopic 
evaluations that follow. 
• Polyp grading of each nasal cavity determined by a nasal polyp grading scale score 
measured by nasoendoscopy (Lildholdt 1995, 1997) as presented in Table 2. The 
baseline assessment of polyp grading is performed at Visit 1 (Day 1/Baseline) by 
the examining physician to determine study eligibility. Assessment of polyp grade 
will be performed by an independent reviewer using the videos from the 
examination.  Subjects and visits will be de-identified for this review. 
 
 
 
 
Table 2:  Nasal Polyp Grading Scale 
Score 
Description 
0 
No polyps 
1 
Mild polyposis - polyps not reaching below the inferior border of the middle 
turbinate 
2 
Moderate polyposis - polyps reaching below the inferior border of the middle 
concha, but not the inferior border of the inferior turbinate 
3 
Severe polyposis - large polyps reaching below the lower inferior border of the 
inferior turbinate 
 
• SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and 
social/emotional consequences of their nasal disorder. Each item is rated as follows: 
0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate 
problem, 4=severe problem, 5=problem as bad as it can be. The recall period is the 
past 2 weeks. The SNOT-22 is validated in chronic rhinosinusitis (Hopkins 2009). 
The SNOT-22 takes approximately 5 minutes to complete. 
 
• The Sniffin’ Sticks n-butanol (Extended test) are used to investigate human 
olfactory performance by use of odor pens.  It consists of 3 different subtests- 
Threshold, Discrimination and Identification. The Threshold test is used to 
ascertain the patient’s olfactory threshold.  The Discrimination test requires the 


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patient to differentiate smells.  The Identification Test requires the patient to 
identify everyday smells by means of a card with different choices. The test will 
take approximately 30-40 minutes. All substances contained in the test are non-
toxic and not harmful in the used concentrations. The result of this test is expressed 
as the sum of the results of the 3 subtests, the so called TDI score (threshold, 
discrimination, identification). Here a score of more than 30 rates as normal, a score 
of 30 or less indicates hyposmia and a score of 15 and below points to functional 
anosmia in the form of a complete loss of the sense of smell or an extremely 
weakened smell ability. 
 
• Subject global impression of change will be assessed using a subject-completed 
PGIC scale as shown in Table 3. The PGIC takes less than 1 minute to complete. 
 
Table 3:  Patient Global Impression of Change (PGIC) Scale 
Since starting the study drug, how would you rate the change in your symptoms? 
Score 
Description 
1 
Very much improved 
2 
Much improved 
3 
Minimally improved 
4 
No change 
5 
Minimally worse 
6 
Much worse 
7 
Very much worse 
 
13 
SAFETY ASSESSMENTS 
Refer to Section 3, Schedule of Study Procedures and Evaluations, for the timing of all safety 
assessments.  
Safety will be assessed by monitoring of AEs throughout the study (as described in Section 
13.4), nasal examinations and measuring vital signs (i.e., blood pressure, pulse), and through 
collection of information for concomitant medications. 
13.1 Nasal Examination 
The nasal examination will be performed via nasoendoscopy. See Section 11, Visit Schedule 
Summary, regarding completion of this assessment, including visit time windows. A summary 
of the worksheet key assessments from the nasal examination is provided in Attachment 2.   


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13.2 Vital Signs 
Vital signs include systolic and diastolic blood pressure measurements and pulse rate. Before 
vital signs are measured, the subject should be at rest for at least 5 minutes.  
13.3 Laboratory Tests 
Laboratory tests, other than the urine pregnancy tests performed at each office visit, are not 
scheduled assessments for this study.  If any laboratory tests are performed as part of a subject’s 
standard of care after the subject is enrolled into the study, and the laboratory test result is 
considered by the investigator to be clinically significant, it should be considered an AE if it 
meets the definition provided in Section 13.4.1.  
13.4 Adverse Event Definitions and Reporting 
13.4.1 Adverse Events 
An AE is any untoward medical occurrence associated with the use of an investigational 
product in humans, whether or not considered related to the investigational product. This 
includes any occurrence that was new in onset or aggravated in severity or frequency from the 
baseline condition.  
In this study, polyp grade and symptoms of nasal polyps are collected as part of the primary 
and secondary endpoints. Changes in polyp grade or worsening of these symptoms should not 
be reported as AEs. All events that meet the definition of a SAE will be reported as SAEs, 
regardless of whether they are protocol-specific assessments.  
Abnormal results of diagnostic procedures, including laboratory test abnormalities, or from the 
nasal examination are considered AEs if they result in: 
• Discontinuation from the study; 
• Require treatment or any other therapeutic intervention; 
• Require further diagnostic evaluation which confirms a clinical significant 
abnormality (excluding a repetition of the same procedure that rules out an 
abnormality); or 
• Are associated with clinical signs or symptoms that would have a significant 
clinical impact, as determined by the investigator. 


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Subjects are encouraged to report AEs spontaneously or in response to general, non-directed 
questioning. All non-serious AEs are to be followed until the subject completes the study or is 
lost to follow-up. 
Timely, accurate, and complete reporting and analysis of safety information from clinical 
studies is crucial for the protection of subjects, is the responsibility of the investigators and the 
Sponsor, and is mandated by regulatory agencies worldwide. 
Each AE is to be documented on the CRF with reference to intensity, date of occurrence, 
duration, frequency, treatment, action taken regarding study drug, and outcome. Furthermore, 
each AE is to be classified as being serious or non-serious. Additionally, the investigator must 
assess whether the AE is drug related (adverse drug reaction) or not. Changes of AEs and dates 
of ending must be documented on the CRF. 
Surgical procedures, planned before enrollment of the subject in the study, are not considered 
AEs if the condition(s) was (were) known before study inclusion. In the latter case, the medical 
condition should be reported in the subject’s medical history. 
For the purposes of this study, the period of observation for collection of AEs extends from 
the time the subject gives informed consent at Visit 1 (Day 1/Baseline) until completion of 
Visit 3 (Week 24 / End of Study/ Early Termination). SAEs will be reported through 30 days 
after the last dose of OPN-375 administration. 
The maximum severity (intensity) of the AE will be categorized by the investigator as shown 
in Table 4. 
Table 4:  Adverse Event Severity 
Code 
Descriptor 
Definition 
1 
Mild 
The subject is aware of the symptom, but easily tolerates it 
2 
Moderate 
The subject has discomfort enough to cause interference with usual activity 
3 
Severe 
The subject is incapacitated to work or perform usual activities 
 
13.4.2 Adverse Reactions 
An AE is considered related to study drug (adverse reaction) if there is evidence to suggest a 
causal relationship between the treatment and the AE. 


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13.4.3 Suspected Adverse Reactions 
“Suspected adverse reactions” means any AE for which there is a reasonable possibility that 
the drug caused the AE. “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the drug and the AE. A “suspected adverse reaction” implies a lesser 
degree of certainty about causality than “adverse reaction” which means any AE caused by a 
drug. 
An AE is considered to be a suspected adverse reaction if: 
• The AE is a single occurrence of an uncommon AE that is known to be strongly 
associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson 
Syndrome).  
• The AE occurs one or more times and is not commonly associated with drug 
exposure, but is otherwise uncommon in the population exposed to the drug 
(e.g., tendon rupture). 
• The AE is part of an aggregate analysis of specific AEs observed in a clinical trial 
(such as known consequences of the underlying disease or condition under 
investigation or other events that commonly occur in the study population 
independent of drug therapy) that indicates those AEs occur more frequently in the 
drug treatment group than in a concurrent or historical control group.  
Suspected adverse reactions are the subset of all AEs for which there is a reasonable possibility 
that the drug caused the event. Inherent in this definition, and in the requirement to report them 
is the need for the Sponsor to evaluate the available evidence and make a judgment about the 
likelihood that the drug actually caused the AE.   
13.4.4 Unexpected Adverse Reactions or Adverse Events 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the IB or 
is not listed at the specificity or severity that has been observed. "Unexpected," as used in this 
definition, also refers to AEs or suspected adverse reactions that are mentioned in the IB as 
occurring with a class of drugs or as anticipated from the pharmacological properties of the 
drug, but are not specifically mentioned as occurring with the particular drug under 
investigation. 
The suspected adverse reactions listed in the IB (i.e., “expected”) are those observed with the 
investigational drug and for which a causal relationship between the event and the drug is 
suspected or confirmed. Thus, AEs that would be anticipated to occur as part of the disease 


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process are considered unexpected for the purposes of reporting because they would not be 
listed in the IB. Additionally, AEs that are listed in the IB as occurring with the same class of 
drugs, or as anticipated from the pharmacological properties of the drug, even though they 
have not been observed with the drug under investigation, will be considered unexpected until 
they have been observed with the drug under investigation.  
13.4.5 Serious Adverse Events 
An AE or suspected adverse reaction is considered “serious” if at any dosage, in the view of 
either the investigator or Sponsor, it meets one or more of the following criteria:  
• Is fatal,  
• Is life-threatening,  
• Results in inpatient hospitalization or prolongation of existing hospitalization,  
• Results in a persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions, or  
• Is a congenital anomaly/birth defect.  
Other important medical events that may not be immediately life-threatening or result in death 
or hospitalization, based upon appropriate medical judgment, are considered SAEs if they are 
thought to jeopardize the subject and/or require medical or surgical intervention to prevent one 
of the outcomes defining an SAE. Since SAEs are critically important for the identification of 
significant safety problems, it is important to take into account both the investigator’s and the 
Sponsor’s assessment. If either the Sponsor or investigator believes that the event is serious, 
the event must be considered serious and evaluated by the Sponsor for expedited reporting. 
All SAEs must be reported to the Sponsor or their designee within 24 hours after the 
investigator becomes aware of the event, along with a determination as to whether it is 
associated with the study drug, EDS, or procedure.  
13.4.6 Life-Threatening Adverse Events 
An AE or suspected adverse reaction is considered “life-threatening” if, in the view of either 
the investigator or Sponsor, its occurrence places the subject at immediate risk of death. It does 
not include an AE or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. As with the definition of serious, the determination of whether an 
AE is life-threatening can be based on the opinion of either the investigator or Sponsor. Thus, 


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if either believes that it meets the definition of life-threatening, it must be considered life-
threatening for reporting purposes.  
13.4.7 Serious Adverse Event Reporting 
All SAEs must be reported within 24 hours to: 
Ashfield Safety and Pharmacovigilance 
Safety Email: APV.AEOptiNose@ashfieldPV.com 
 
Safety Fax: 1-866-391-0765 
 
  
Note: If the contact information above changes during the course of the study, written 
notification will be provided by the Sponsor or their designee to the investigator, and a 
protocol amendment will not be required. 
It is imperative that Ashfield be informed within 24 hours after the investigator becomes aware 
of a SAE so that reporting to the Regulatory Agencies can be met within the required time 
frame (7 or 15 calendar days). 
Should the investigator become aware of an SAE (regardless of relationship to study drug) that 
occurs during the study or within 30 days after stopping the study drug, the SAE must be 
reported in accordance with the procedures specified in this protocol. All SAEs that are not 
resolved by the end of the study, or that were not resolved upon discontinuation of the subject’s 
participation in the study, are to be followed until either: the AE resolves, the AE stabilizes, 
the AE returns to baseline values (if a baseline value is available), or it is shown that the AE is 
not attributable to the study drug or study conduct. 
Medical and scientific judgment is to be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as for important medical events that were not immediately 
life-threatening or did not result in death or hospitalization but are jeopardizing the subject or 
require intervention to prevent one of the outcomes listed above.  
13.4.8 Non-Serious Adverse Event Reporting 
Non-Serious AEs will be recorded in the clinical data base in a timely manner to permit review 
by the Sponsor. 


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13.4.9 Pregnancy 
Following administration of study drug, pregnancy cases in any female subject will be reported 
if known until the subject completes or withdraws from the study. The pregnancy will be 
reported immediately by phone and by faxing/emailing a completed Pregnancy Report to the 
Sponsor or their designee within 24 hours of knowledge of the event. The pregnancy will not 
be processed as an SAE; however, the investigator will follow the subject until completion of 
the pregnancy and must assess the outcome in the shortest possible time but not more than 
30 days after completion of the pregnancy. The investigator should notify the Sponsor or their 
designee of the pregnancy outcome by submitting a follow-up Pregnancy Report. If the 
outcome of the pregnancy meets the criteria for immediate classification of an SAE 
(e.g., spontaneous or therapeutic abortion [any congenital anomaly detected in an aborted fetus 
is to be documented], stillbirth, neonatal death, or congenital anomaly), the investigator will 
report the event by phone and by faxing/emailing a completed SAE form to the Sponsor or 
designee within 24 hours of knowledge of the event. Pregnancy in the partners of research 
subjects does not need to be reported. 
14 
STATISTICAL ANALYSIS 
Data will be summarized descriptively. Listings will be produced using SAS® Version 9.0 or 
higher. No inferential statistics will be performed for this study.   
14.1 Sample Size Determination 
No statistical sample size calculation was performed for this study.  An empiric sample size of 
10 subjects is considered to be adequate to assess changes in polyp size and mucosal edema as 
assessed by nasoendoscopic video, as well as for symptomatic endpoints. 
14.2 Analysis Datasets 
Safety Population 
The safety population will include all subjects who receive at least 1 dose of study drug.  


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14.3 Endpoint Evaluation 
Nasal polyp grading score, SNOT-22 (item and total), Sniffin’ Sticks n-butanol (Extended test) 
TDI scores, and PCIG for each timepoint will be listed for each subject.   
14.4 Safety Analysis 
All reported AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 13.1 or higher. All AEs during the study period for each subject will be 
listed and the listing will include the verbatim term, System Organ Class [SOC], preferred 
term, AE start date, AE end date, severity, serious categorization, causality, action taken if any, 
and outcome. 
Vital signs will be listed for each subject. 
Concomitant medications will be coded using the World Health Organization (WHO) Drug 
Dictionary (WHODrug), Version December 2010 or later, and listed by subject.  
14.5 Interim Analysis 
No interim analysis is planned for this study. 
15 
DATA HANDLING AND RECORD KEEPING 
15.1 Case Report Forms 
Clinical data will be entered on case report forms (CRFs) for transmission to the Sponsor or 
their designee. Data on CRFs must correspond to and be supported by source documentation 
maintained at the study center. All study forms and records transmitted to the Sponsor or their 
designee must carry only coded identifiers such that personally identifying information is not 
transmitted.  
Any changes made to data after collection will be made through the use of Data Clarification 
Forms (DCF). Data reported on the CRFs, which are derived from source documents, should 
be consistent with the source documents or the discrepancies should be explained. CRFs will 
be considered complete when all missing and/or incorrect data have been resolved.  


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15.2 Source Documents 
Source documents are considered to be all information in original records and certified copies 
of original records of clinical findings, observations, data or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. 
The investigator agrees to allow inspections of the study site and any source documentation, 
by clinical research and audit personnel from the Sponsor or their designee, and external 
auditors or representatives of regulatory authorities. Direct access to the subject’s 
medical/clinical records is necessary to verify and corroborate the data recorded on the CRFs.  
15.3 Record Retention 
Study records and source documents need to be preserved for at least 15 years after the 
completion or discontinuation of/withdrawal from the study or 2 years after the last approval 
of a marketing application in an ICH region which includes the study report, whichever is the 
longer time period. 
16 
MONITORING 
The study will be monitored to ensure that the study is conducted and documented properly 
according to the protocol, Good Clinical Practice (GCP), and all applicable regulatory 
requirements.  
On-site visits will be made at appropriate times during the period of the study. Monitors 
(e.g., Clinical Research Associates) must have direct access to source documentation in order 
to check the consistency of the data recorded in the CRFs. Additionally, remote monitoring 
may be conducted. 
The investigator will make available to the Monitor source documents, medical records, and 
source data necessary to complete CRFs. In addition, the investigator will work closely with 
the Monitor and, as needed, provide them appropriate evidence that the conduct of the study is 
being done in accordance with applicable regulations and GCP guidelines.  


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17 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor or their designee will perform the quality assurance and quality control activities 
of this study; however, responsibility for the accuracy, completeness, and reliability of the 
study data presented to the Sponsor lies with the Principal Investigator.  
The Sponsor may arrange audits as part of the implementation of quality assurance to ensure 
that the study is being conducted in compliance with the protocol, Standard Operating 
Procedures, GCP, and all applicable regulatory requirements. Audits will be independent of 
and separate from the routine monitoring and quality control functions. 
18 
PROTOCOL AMENDMENT AND PROTOCOL DEVIATION  
18.1 Protocol Amendment 
A protocol amendment will be required if changes to a protocol significantly affect the safety 
of subjects, the scope of the investigation, or the scientific quality of the study. Protocol 
amendments must not be implemented without prior IRB approval, except when necessary to 
eliminate immediate hazards to the subjects. If a protocol change is implemented immediately 
to protect the subjects, the IRB and regulatory authority must be subsequently notified. 
Documentation of amendment approval by the investigator and IRB must be provided to the 
Sponsor or their designee. When the change(s) involves only administrative aspects of the 
study, the IRB only needs to be notified. 
18.2 Protocol Deviations 
No deviations from the protocol are anticipated. However, should a protocol deviation occur, 
the Sponsor or their designee must be informed as soon as possible. Protocol deviations and/or 
violations and the reasons they occurred will be included in the study report. Reporting of 
protocol deviations to the IRB and in accordance with applicable regulatory authority mandates 
is an investigator responsibility. 


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19 
ETHICAL CONSIDERATIONS 
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, Subpart D, of 
Title 21 of the Code of Federal Regulations (CFR), and in compliance with GCP guidelines. 
Institutional Review Boards will review and approve this protocol and informed consent. All 
subjects are required to give written informed consent prior to participation in the study. This 
study will be performed in accordance with GCP by qualified investigators. The study 
specifically incorporates the following features: 
• Multi-center, open-label, study design; 
• Prospectively stated objectives and analytical plan; 
• Accepted, pre-specified outcome measures for safety and efficacy; 
• Site initiation meeting prior to study start and a detailed protocol to promote 
consistency across sites; and 
• Compliance with GCP, with assessment via regular monitoring. 
Quality assurance procedures will be performed at study sites and during data management to 
assure that safety and efficacy data are adequate and well documented. 
20 
FINANCING AND INSURANCE 
Financial aspects of the study are addressed in a separate clinical study agreement.  
The investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The Sponsor will provide insurance coverage for the clinical study as 
required by national regulations.  
21 
PRIVACY OF PERSONAL DATA 
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to investigate the efficacy, safety, quality, and utility of 
the investigational product(s) used in this study. These data must be collected and processed 
with adequate precautions to ensure confidentiality and compliance with applicable data 
privacy protection laws and regulations. The Sponsor ensures that the personal data are  
• processed fairly and lawfully 


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• collected for specified, explicit, and legitimate purposes and not further processed 
in a way incompatible with these purposes 
• adequate, relevant, and not excessive in relation to said purposes 
• accurate and, where necessary, kept up to date 
Explicit consent for the processing of personal data will be obtained from the participating 
subject before collection of data. Such consent should also address the transfer of the data to 
other entities and to other countries. The subject has the right to request through the investigator 
access to his/her personal data and the right to request rectification of any data that are not 
correct or complete. Reasonable steps should be taken to respond to such request, taking into 
consideration the nature of the request, the conditions of the study, and the applicable laws and 
regulations. Appropriate technical and organizational measures to protect the personal data 
against unauthorized disclosures or access, accidental or unlawful destruction, or accidental 
loss or alteration must be put in place. Sponsor personnel (or their designee) whose 
responsibilities require access to personal data agree to keep the identity of study subjects 
confidential. 
22 
PUBLICATION POLICY 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
The investigator should be aware that intellectual property rights (and related matters) 
generated by the investigator and others performing the clinical study will be subject to the 
terms of a clinical study agreement that will be agreed between the Institution and the Sponsor 
or their designee. With respect to such rights, the Sponsor or their designee will solely own all 
right and interest in any materials, data, and intellectual property rights developed by 
investigators and others performing the clinical study described in this protocol, subject to the 
terms of any such agreement. In order to facilitate such ownership, investigators will be 
required to assign all such inventions either to their Institution or directly to the Sponsor or 
their designee, as will be set forth in the clinical study agreement. 


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23 
REFERENCES 
Aggarwal R, Cardozo A, Homer JJ. The assessment of topical nasal drug distribution. Clin Otolaryngol 
Allied Sci. 2004;29(3):201-5. 
Beconase® AQ [prescribing information] Research Triangle Park, NC: GlaxoSmithKline; 2005. 
Chaaban MR, Walsh EM, Woodworth BA. Epidemiology and differential diagnosis of nasalpolyps. Am J 
Rhinol Allergy. 2013;27(6):473-478. 
Crim C, Pierre L, Daley-Yates,P. A review of the pharmacology and pharmacokinetics of inhaled fluticasone 
propionate and mometasone furoate. Clin Thera 2001: 23(9):1339-1354. 
Fokkens WJ, Lund VJ, Mullol J, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. 
Rhinology 2012;50(suppl 23): 1-298. 
Hopkins C, Slack R, Lund V, et al. Long-term outcomes from the English national comparative audit of 
surgery for nasal polyposis and chronic rhinosinusitis. Laryngoscope. 2009;119(12):2459-65. 
Lildholdt T, Rundcrantz H, Lindqvist N. Efficacy of topical corticosteroid powder for nasal polyps: a double-
blind, placebo-controlled study of budesonide. Clin Otolaryngol. 1995;20:26-30. 
Lildholdt T, Rundcrantz H, Bende M, Larsen K. Glucocorticoid treatment for nasal polyps. The use of topical 
budesonide, intramuscular betamethasone, and surgical treatment. Arch Otolaryngol Head Neck Surg. 
1997;123:595-600. 
Meltzer EO, Hamilos DL, Hadley JA et al. Rhinosinusitis: establishing definitions for clinical research and 
patient care. J Allergy Clin Immunol 2004; 114(6 Suppl):155-212. 
Nasonex (mometasone furoate) [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; 2013. 
 


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24 
 ATTACHMENT 1: BECLOMETASONE – EQUIVALENT DOSES 
 


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25 
ATTACHMENT 2: KEY ASSESSMENTS FOR NASAL EXAMINATION 
The nasal examination worksheet will be provided to the sites as a separate document. The worksheet 
is formatted as a series of questions with check boxes and fields for narrative text. The nasal 
examination worksheet will be completed by the physician who performs the examination. If 
decongestants and/or local anesthetics are administered as preparation for the nasoendoscopy, these 
will be recorded on the form. Please note that if decongestants and/or local anesthetics are administered 
for the initial Visit 1 (Day 1/Baseline) nasoendoscopy for a subject, the same must be used for each 
subsequent examination. A rigid endoscope must be used. The size of the endoscope chosen for the 
initial Visit 1 (Day 1/Baseline) examination for each subject should be used throughout the study. The 
investigator will use the information from the nasal examination worksheet to complete the nasal 
examination, and concomitant medication case report forms (CRFs).  
EPISTAXIS  
• 
Non-active bleeding, but evidence of recent bleeding (e.g., darker blood, appearing 
thicker or ‘solid’ as clots) 
• 
Active bleeding  
 blood tinged mucus 
 mild bleeding, medical intervention not indicated 
 clinically evident bleeding, medical intervention necessary  
• 
Origin of bleeding  
• 
Is the bleeding related to injury/nasal trauma?  
SEPTAL EROSION/PERFORATION  
• 
Location  
 anterior, including the nasal valve area  
 posterior to nasal valve  
 both 
• 
Severity 
 evidence of epithelial erosion  
 evidence of ulceration through the epithelial layer with exposed cartilage  
 perforation 
• 
Is the septal perforation related to injury/trauma? 
ULCERATION / EROSION (located in area other than septum) 
• 
Severity 
 epithelial surface abnormally eroded/abraded, but not clinically significant and 
expected to resolve rapidly     
 deeper than surface abrasion, limited clinical significance but may require 
monitoring or recommendation for routine care   
 deeper ulcers with possible effect on underlying structures, depth is clinically 
significant, intervention or specific care may be warranted   
 
 
LOCAL ANESTHETICS AND / OR DECONGESTANTS ADMINISTERED FOR 
ENDOSCOPY WILL BE RECORDED