Nasal Polyps
Conditions
Brief summary
This study will evaluate the effectiveness and safety of MFNS in improving nasal congestion/obstruction and in reducing bilateral nasal polyps.
Interventions
MFNS, 200 mcg BID administered as two 50 mcg sprays in each nostril BID for up to 16 weeks
DRUGPlacebo for MFNS
Two sprays in each nostril BID for up to 16 weeks
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be Chinese * Must have a diagnosis of bilateral nasal polyps * Clinically significant nasal congestion/obstruction must be present * Must be in good health, free of any clinically significant disease that would interfere with the study schedule or procedures, or compromise the participant's safety * Must have negative urine pregnancy test * Must be using or agree to use a medically accepted method of contraception prior to Screening and during the study
Exclusion criteria
* Have a history of seasonal allergic rhinitis within the last two years * Have had sinus or nasal surgery within the past six months * Have presumed fibrotic nasal polyps * Have had three or more nasal surgeries * Have had any surgical procedure that prevents an accurate grading of the polyps * Complete (or near complete) nasal obstruction * Have acute sinusitis, concurrent nasal infection or have had a nasal infection within two weeks * Have ongoing rhinitis medicamentosa * Have Churg Strauss syndrome (vasculitis, asthma, fever, and eosinophilia) * Have dyskinetic ciliary syndromes, eg, Young's syndrome (sinopulmonary infections and obstructive azoospermia) or Kartagener's syndrome (immobile cilia) * Have been treated within the last 4 weeks with intranasal steroids * Have used any investigational drug in the last 30 days * Have a hypersensitivity to corticosteroids or are allergic to aspirin * Have an ongoing upper respiratory tract infection or had an upper respiratory tract infection within two weeks * Have a nasal septal deviation needing corrective surgery * Have a nasal septal perforation * Have asthma that required in-patient hospitalization for asthma control within six months, required ventilator support for respiratory failure secondary to their asthma within the last five years, required admission to the hospital for management of airway obstruction on two or more occasions within the past year, or required use of more than 14 days of systemic steroid use in previous six months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Congestion/Obstruction Score | Baseline and Weeks 1-4 | At Baseline, the Investigator and participant jointly evaluated the signs and symptoms of congestion/obstruction. After Baseline, participants scored the signs and symptoms of congestion/obstruction every morning immediately prior to dosing using a morning instantaneous congestion/obstruction score. This score reflected the participant's condition at that time (instantaneous) and ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3= severe), with a lower score indicating less congestion/obstruction. Congestion/obstruction scores were averaged over Weeks 1-4 of the treatment period. Data are compared using Least Square (LS) Means. LS Mean Change from Baseline = LS Mean Score averaged over Weeks 1-4 - LS Mean Score for Baseline. |
| Change From Baseline in Total Polyp Size Score | Baseline and Week 16 | An endoscopic nasal examination was performed by the Investigator. Bilateral nasal polyps were scored as follows for each notril (left and right): 0=no polyps, 1=polyps in middle meatus not reaching below inferior border of middle turbinate, 2=polyps reaching below inferior border of middle turbinate but not inferior border of inferior turbinate, 3=large polyps reaching to or below the lower borders of the inferior turbinate or polyps medial to the middle turbinate. Total polyp size score ranged from 0 to 6 (scored 0 to 3 for each nostril), with a lower score indicating smaller-sized polyps. LS Mean Change from Baseline = LS Mean Score for Week 16 - LS Mean Score for Baseline. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MFNS Participants receive MFNS 200 mcg BID for 16 weeks | 375 |
| Placebo Participants receive matching placebo nasal spray BID for 16 weeks | 373 |
| Total | 748 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Disease Progress | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 9 |
| Overall Study | Participant Leaving Country | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 7 |
| Overall Study | Withdrawal by Subject | 13 | 12 |
Baseline characteristics
| Characteristic | MFNS | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 13.49 | 46.8 years STANDARD_DEVIATION 13.75 | 46.8 years STANDARD_DEVIATION 13.61 |
| Sex: Female, Male Female | 151 Participants | 134 Participants | 285 Participants |
| Sex: Female, Male Male | 224 Participants | 239 Participants | 463 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 375 | 0 / 373 |
| serious Total, serious adverse events | 2 / 375 | 3 / 373 |
Outcome results
Primary
Change From Baseline in Congestion/Obstruction Score
At Baseline, the Investigator and participant jointly evaluated the signs and symptoms of congestion/obstruction. After Baseline, participants scored the signs and symptoms of congestion/obstruction every morning immediately prior to dosing using a morning instantaneous congestion/obstruction score. This score reflected the participant's condition at that time (instantaneous) and ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3= severe), with a lower score indicating less congestion/obstruction. Congestion/obstruction scores were averaged over Weeks 1-4 of the treatment period. Data are compared using Least Square (LS) Means. LS Mean Change from Baseline = LS Mean Score averaged over Weeks 1-4 - LS Mean Score for Baseline.
Time frame: Baseline and Weeks 1-4
Population: The Full Analysis Set (FAS) population consisted of all randomized participants who received at least one dose of study treatment and who had a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MFNS | Change From Baseline in Congestion/Obstruction Score | -0.56 score on a scale | Standard Error 0.03 |
| Placebo | Change From Baseline in Congestion/Obstruction Score | -0.42 score on a scale | Standard Error 0.03 |
p-value: 0.000795% CI: [-0.22, -0.06]ANCOVA
Primary
Change From Baseline in Total Polyp Size Score
An endoscopic nasal examination was performed by the Investigator. Bilateral nasal polyps were scored as follows for each notril (left and right): 0=no polyps, 1=polyps in middle meatus not reaching below inferior border of middle turbinate, 2=polyps reaching below inferior border of middle turbinate but not inferior border of inferior turbinate, 3=large polyps reaching to or below the lower borders of the inferior turbinate or polyps medial to the middle turbinate. Total polyp size score ranged from 0 to 6 (scored 0 to 3 for each nostril), with a lower score indicating smaller-sized polyps. LS Mean Change from Baseline = LS Mean Score for Week 16 - LS Mean Score for Baseline.
Time frame: Baseline and Week 16
Population: The FAS population consisted of all randomized participants who received at least one dose of study treatment and who had a baseline and at least one post-baseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MFNS | Change From Baseline in Total Polyp Size Score | -0.76 score on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in Total Polyp Size Score | -0.45 score on a scale | Standard Error 0.05 |
p-value: <0.000195% CI: [-0.45, -0.15]Constrained longitudinal data analysis