Clinical Trials Register

Summary
EudraCT Number:	2011-004887-31
Sponsor's Protocol Code Number:	OPN-FLU-NP-3102
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-08-27
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2011-004887-31

A.3

Full title of the trial

A 16-Week RaNdomized, Double-Blind, Placebo-Controlled, PArallel-Group, Multicenter Study EValuatInG the Efficacy and Safety of Intranasal Administration of 100, 200, and 400 μg of FluticAsone Propionate Twice a Day (BID) Using a Novel
Bi-DirecTional DEvice in Subjects with Bilateral Nasal Polyposis Followed by an 8-Week Open-Label Extension Phase to Assess Safety

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Not applicable

A.3.2

Name or abbreviated title of the trial where available

NAVIGATE II

A.4.1

Sponsor's protocol code number

OPN-FLU-NP-3102

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01624662

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	OptiNose US, Inc
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	OptiNose US, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	OptiNose US, Inc
B.5.2	Functional name of contact point	Sr Director Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	1010 Stony Hill Road, Ste 375
B.5.3.2	Town/ city	Yardley
B.5.3.3	Post code	PA 19067
B.5.3.4	Country	United States
B.5.4	Telephone number	+1267 364-3507
B.5.5	Fax number	+1267 395 2119
B.5.6	E-mail	colette.kosik-gonzalez@optinose.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	OPTINOSE FLUTICASONE
D.3.2	Product code	OPTINOSE FLUTICASONE
D.3.4	Pharmaceutical form	Nasal spray, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intranasal use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUTICASONE PROPIONATE
D.3.9.1	CAS number	80474-14-2
D.3.9.2	Current sponsor code	FLUTICASONE PROPIONATE
D.3.9.3	Other descriptive name	FLUTICASONE PROPIONATE
D.3.9.4	EV Substance Code	SUB02241MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.022
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	OPTINOSE FLUTICASONE
D.3.2	Product code	OPTINOSE FLUTICASONE
D.3.4	Pharmaceutical form	Nasal spray, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intranasal use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUTICASONE PROPIONATE
D.3.9.1	CAS number	80474-14-2
D.3.9.2	Current sponsor code	FLUTICASONE PROPIONATE
D.3.9.3	Other descriptive name	FLUTICASONE PROPIONATE
D.3.9.4	EV Substance Code	SUB02241MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.090
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Nasal spray, suspension
D.8.4	Route of administration of the placebo	Intranasal use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Bilateral Nasal Polyposis

E.1.1.1

Medical condition in easily understood language

Bilateral Nasal Polyposis

E.1.1.2

Therapeutic area

Diseases [C] - Ear, nose and throat diseases [C09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10028754
E.1.2	Term	Nasal polyp
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to compare the efficacy of intranasal administration of 100, 200, and 400 μg of fluticasone propionate twice a day delivered by the OptiNose device with placebo in subjects with bilateral nasal polyposis. Two co-primary endpoints will be used in the study: reduction of nasal congestion/obstruction symptoms at the end of Week 4 of the double-blind treatment phase measured by the 7-day average instantaneous AM diary symptom scores, and reduction in total polyp grade (sum of scores from both nasal cavities) over the 16 weeks of the double-blind treatment phase as determined by a nasal polyp grading scale score measured by nasoendoscopy.

E.2.2

Secondary objectives of the trial

To compare the effect of intranasal administration of fluticasone propionate twice a day during the double-blind treatment phase (DBTP) of the study with placebo on:
• Change in polyp grade
• Change in nasal congestion/obstruction symptoms, sense of smell, rhinorrhea symptoms, and facial pain or pressure symptoms
• Change in subject symptoms and functioning
• Change in nasal patency
• Change in monthly use of rescue medication
• In subjects with comorbid asthma, change:
- in asthma symptoms
- in forced expiratory volume in 1 second (FEV-1)
• Change in patient-reported outcomes
• Improvement in sleep quality
• Assessment of health economic measures related to bilateral nasal polyposis
• Subject assessment of current/most recent nasal spray and of the study drug
• Subject assessment of Patient Global Impression of Change (PGIC)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Men or women aged 18 years and older
• Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal cavities as determined by a nasal polyp grading scale score measured by nasoendoscopy at Visit 1 (Screening)
• Must have at least moderate symptoms (as defined in the protocol) of nasal congestion/obstruction as reported by the subject, on average, for the 7 day period preceding Visit 1 (Screening)
• At Visit 2, Day 1 (Baseline), must have a morning score of at least 2 (moderate) on nasal congestion/obstruction recorded on the subject diary for at least 5 of the last 7 days of the 7- to up to 14 day run-in period
• Must demonstrate an ability to correctly complete the daily diary during the run-in period to be eligible for randomization
• Subjects with comorbid asthma or chronic obstructive pulmonary disease (COPD) must be stable with no exacerbations (eg, no emergency room visits, hospitalizations, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). 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 Visit 1 (Screening) with plans to continue use throughout the study.
• Must be able to cease treatment with intranasal medications including, but not limited to, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium bromide, inhaled corticosteroids (except permitted doses listed above for comorbid asthma and COPD) at Visit 1 (Screening)
• Must be able to cease treatment with oral and nasal decongestants and antihistamines at Visit 1 (Screening)
• Must be able to use the OptiNose device correctly; all subjects will be required to demonstrate correct use of the practice placebo device at Visit 1 (Screening)

E.4

Principal exclusion criteria

• Have complete or near-complete obstruction of the nasal cavities
• Inability to achieve bilateral nasal airflow for any reason including nasal septum deviation
• Inability to have each nasal cavity examined for any reason including nasal septum deviation
• Nasal septum perforation
• Has had more than 1 episode of epistaxis with frank bleeding in the month before Visit 1 (Screening)
• Have evidence of significant mucosal injury, ulceration or erosion (eg, exposed cartilage, perforation) on Visit 1 (Screening) nasal examination/nasoendoscopy
• History of more than 5 sinonasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime)
• History of sinus or nasal surgery within 6 months before Visit 1 (Screening)
• History of any surgical procedure that prevents the ability to accurately grade polyps
• Have symptoms of seasonal allergic rhinitis at Visit 1 (Screening) or Visit 2, Day 1 (Baseline) and/or, based on time of year, would anticipate onset of symptoms within 4 weeks of randomization
• Purulent nasal infection, acute sinusitis, or upper respiratory tract infection within 2 weeks before Visit 1 (Screening). Potential subjects presenting with any of these infections may be rescreened 4 weeks after symptom resolution
• Planned sinonasal surgery during the period of the study
• History or current diagnosis of any form of glaucoma or ocular hypertension (ie, >21 mmHg)
• History of intraocular pressure elevation on any form of steroid therapy
• Current diagnosis of the presence (in either eye) of a cataract of Grade 1 or greater as defined on the Eye Examination Worksheet (see Attachment 2) OR, less than a Grade 1 cataract with associated visual impairment

E.5 End points

E.5.1

Primary end point(s)

• Mean change from baseline to the end of Week 4 of the double-blind treatment phase in average instantaneous AM nasal congestion/obstruction scores; scores are the averaged instantaneous AM scores over the 7 days before Visit 2, Day 1 (Baseline) and over the 7 days before the Week 4 visit from the subject diary
• Mean change from baseline over the 16 weeks of the double-blind treatment phase in total polyp grade (sum of scores from both nasal cavities) as determined by a nasal polyp grading scale score measured by nasoendoscopy

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

• Mean change from baseline to Week 4, 8, 12, 16, end of double-blind treatment phase, and Week 24/end of open-label extension phase in polyp grade (total and worst nostril) as determined by a nasal polyp grading scale score measured by nasoendoscopy
• Mean change from baseline to Week 4, 8, 12, 16, and the end of the double-blind treatment phase:
• in average instantaneous and reflective AM scores and in average instantaneous and reflective PM scores, averages are based on scores recorded in the diary for the 7 days before each time point for:
- nasal congestion/obstruction score
- sense of smell score
- rhinorrhea score
- facial pain or pressure score
Note: For the nasal congestion/obstruction score, the instantaneous AM score for the end of Week 4 of the double-blind treatment phase time point is also part of the co-primary endpoint.
• in the Sinonasal Outcome Test - 22 (SNOT-22) total score (also calculated at Week 24/end of open-label extension phase)
• in the SNOT-22 nasal symptom-related items score; items 1, 2, 3, 5, 6, 21, and 22 (also calculated at Week 24/end of open-label extension phase)
• in peak nasal inspiratory flow (PNIF)
• For subjects with comorbid asthma:
• in Asthma Control Test (ACT) total score
• in FEV-1
• Average monthly use of rescue medication (loratadine or another country-available, non sedating antihistamine) after the Week 4 visit during the double-blind treatment phase
• The proportions of subjects who have reductions in the AM and PM, instantaneous and reflective, average nasal congestion/obstruction symptom scores by 0.5 or more points from baseline to the end of the double blind treatment phase
• The proportion of subjects who have a reduction in the total polyp grade score (sum of scores from both nasal cavities) by 1 or more points from baseline to the end of the double-blind treatment phase
• Mean change from baseline to the end of the double-blind treatment phase for:
• Rhinosinusitis Disability Index (RSDI) total score
• 36-Item Short Form Health Survey version 2 (SF-36v2) scores (also calculated at Week 24/end of open-label extension phase)
• Mean change from baseline to Week 4, 8, 12, 16, and the end of the double-blind treatment phase in the Medical Outcomes Study Sleep Scale – Revised (MOS Sleep-R) scores
• Comparison of health economic measures during the double-blind treatment and open-label extension phases related to bilateral nasal polyposis (eg, criteria for surgical intervention for nasal polyps is met [independent of actual surgery performed], missed work or school days/lost productivity)
• Subject evaluation of current/most recent nasal spray at screening and subject evaluation of study drug during double-blind treatment and open-label extension phases will be summarized
• Patient Global Impression of Change (PGIC) scores at Week 4, 16, and 24 will be summarized

E.5.2.1

Timepoint(s) of evaluation of this end point

For timepoints please refer to protocol, Section 9.2.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

8-Week Open-Label Extension Phase

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

European Union

South Africa

Ukraine

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of last subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

320

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

320

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

301

F.4.2.2

In the whole clinical trial

320

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

not different from the expected normal treatment of that condition

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-10-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-07-03

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