Nasal Polyps
Conditions
Keywords
Nasal Polyposis, Asthma, Nasal polyp score (NPS), Nasal congestion score (NCS), Bronchial Diseases, Lung Diseases, Nose Diseases, Respiratory Hypersensitivity, Fevipiprant, QAW039
Brief summary
A Phase 3b Proof-of-Concept study to evaluate the ability of fevipiprant 150 mg and 450 mg, compared with placebo, as add-on to nasal spray standard-of-care (SoC), in reducing endoscopic nasal polyp score in adult (≥ 18 years) patients with nasal polyposis and concomitant asthma.
Detailed description
This was a Phase 3b, Proof-of-concept study with a randomized, multicenter, double-blind, placebo-controlled, parallel-group study design to determine the ability of fevipiprant plus standard of care (SoC) compared to placebo plus SoC to reduce the size of nasal polyps. The study enrolled adult male and female patients diagnosed with nasal polyposis with a nasal polyp score assessed by nasal endoscopy ≥ 4 at baseline with a minimum score of 2 in each nostril and a concomitant diagnosis of asthma. Patients who meet the inclusion/exclusion criteria were randomized in 1:1:1 ratio in either of the 3 arms fevipiprant 450 mg dose once daily (o.d.), fevipiprant 150 mg dose o.d. or placebo o.d. in addition to SoC (mometasone furoate spray). The study included: * a Screening period of 2 weeks to assess eligibility * a Run-in period of 4 weeks where patients utilized mometasone furoate spray (200 μg once daily, administered as two 50 μg actuations into each nostril) * a Treatment period of 16 weeks. Patients continued to use the mometasone furoate SoC throughout the treatment period. * a Follow-up period of 2 weeks following the last dose of study drug to collect additional data for safety variables. The purpose of this study was to evaluate the efficacy and safety of fevipiprant 150 mg and 450 mg compared to placebo in the reduction of nasal polyps size and the effect on symptoms, quality of life and smell via patient-reported outcomes in patients with nasal polyposis and concomitant asthma.
Interventions
DRUGPlacebo
Placebo once daily administered orally as tablet
DRUGFevipiprant 150 mg
Fevipiprant (QAW039) 150 mg once daily administered orally as tablet
DRUGFevipiprant 450 mg
Fevipiprant (QAW039) 450 mg once daily administered orally as tablet
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind, double dummy study design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged 18 years or more with a diagnosis of nasal polyps with Nasal polyp score \>= 4 with minimum score of 2 in each nostril. * Concomitant diagnosis of asthma for a period of at least 6 months prior to screening. * Patients on stable asthma treatment of at least inhaled corticosteroids (any dose) alone for at least 6 months prior to screening or ICS for 6 months prior to screening with any required, inhaled medication (LABA, LAMA) added at least 6 weeks prior to screening.
Exclusion criteria
* Asthma exacerbation, within 6 weeks prior to screening, that required systemic corticosteroids, hospitalization or emergency room visit. * Chronic/maintenance use of oral corticosteroids (OCS) defined as any continuous use of OCS for a period of 1 month or more, within 1 year of screening * Use of biologics for asthma or any other indications, that has the potential to interfere/affect either asthma or nasal polyposis disease progression, within 6 months of screening. * Use of medication for sino-nasal symptoms (antibiotics with or without OCS) within 30 days of screening or during the run-in period. * Use of tetracycline or macrolide antibiotics specifically, within 8 weeks of screening. * History of nasal surgery modifying the structure of the nose such that assessment of the nasal polyp score is not possible. * Patients with baseline ACQ-5≥1.5
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Nasal Polyp Score at Week 16 | Baseline, Week 16 | Nasal Polyp Score (NPS) is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Total score ranges from 0 to 8 (scored 0 \[no polyp\] to 4 \[large polyps\] for each nostril), with a lower score indicating smaller-sized polyps. Baseline NPS is defined as the last measurement performed on or before the date of randomization. A negative change from baseline in NPS is considered a favorable outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Nasal Congestion Score at Week 16 | Baseline, Week 16 | The nasal congestion score (NCS) is assessed via a questionnaire where patients are asked Is your nose blocked? with responses ranging from 0 = not at all, to 3=severe. Baseline NCS is defined as the last assessment performed on or before the date of randomization. A negative change from baseline in NCS is considered a favorable outcome. |
| Change From Baseline in Quality of Life as Assessed by the SNOT-22 Questionnaire at Week 16 | Baseline, Week 16 | SNOT-22 (Sino-Nasal Outcome Test) Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been for them over the past 2 weeks on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. Baseline SNOT-22 is defined as the last assessment performed on or before the date of randomization. A negative change from baseline in SNOT-22 is considered a favorable outcome. |
| Change From Baseline in Sense of Smell as Assessed by the University of Pennsylvania Smell Identification Test (UPSIT) at Week 16 | Baseline, Week 16 | The UPSIT (University of Pennsylvania Smell Identification Test) is a test that measures an individual's ability to detect odors. It consists of 4 workbooks of 10 pages each. On each page there is a different scratch and sniff strip which is embedded with a microencapsulated odorant and a question regarding the smell detected with a four-choice option for the response. The total number of questions in UPSIT is 40. The number of correct responses regarding the smells being experienced is summed to provide a total score that ranges from 0 to 40, with a higher score indicating a better sense of smell. Baseline UPSIT is defined as the last assessment performed on or before the date of randomization. A positive change from baseline in UPSIT is considered a favorable outcome. |
Countries
Argentina, Belgium, Canada, Czechia, Germany, Italy, Netherlands, Poland, United States
Participant flow
Recruitment details
Participants took part in 25 investigative sites in 9 countries.
Pre-assignment details
After the screening, participants went through a Run-in period of 4 weeks where they utilized mometasone furoate spray into each nostril. Afterwards, patients were randomized in 1:1:1 ratio in either of the 3 arms and continued to use the mometasone furoate spray.
Participants by arm
| Arm | Count |
|---|---|
| Fevipiprant 150 mg Fevipiprant (QAW039) 150 mg once daily orally | 32 |
| Fevipiprant 450 mg Fevipiprant (QAW039) 450 mg once daily orally | 34 |
| Placebo Placebo once daily orally | 32 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Subject decision | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Fevipiprant 150 mg | Fevipiprant 450 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 13.36 | 50.9 years STANDARD_DEVIATION 13.1 | 48.5 years STANDARD_DEVIATION 13.43 | 50.1 years STANDARD_DEVIATION 13.2 |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 32 Participants | 34 Participants | 31 Participants | 97 Participants |
| Sex: Female, Male Female | 16 Participants | 15 Participants | 12 Participants | 43 Participants |
| Sex: Female, Male Male | 16 Participants | 19 Participants | 20 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 34 | 0 / 32 |
| other Total, other adverse events | 17 / 32 | 13 / 34 | 11 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 34 | 0 / 32 |
Outcome results
Primary
Change From Baseline in Nasal Polyp Score at Week 16
Nasal Polyp Score (NPS) is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Total score ranges from 0 to 8 (scored 0 \[no polyp\] to 4 \[large polyps\] for each nostril), with a lower score indicating smaller-sized polyps. Baseline NPS is defined as the last measurement performed on or before the date of randomization. A negative change from baseline in NPS is considered a favorable outcome.
Time frame: Baseline, Week 16
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fevipiprant 150 mg | Change From Baseline in Nasal Polyp Score at Week 16 | 0.20 score on scale | Standard Error 0.224 |
| Fevipiprant 450 mg | Change From Baseline in Nasal Polyp Score at Week 16 | -0.10 score on scale | Standard Error 0.216 |
| Placebo | Change From Baseline in Nasal Polyp Score at Week 16 | 0.14 score on scale | Standard Error 0.233 |
p-value: 0.97995% CI: [-0.59, 0.7]Mixed Model for Repeated Measures (MMRM)
p-value: 0.65695% CI: [-0.88, 0.39]MMRM
Secondary
Change From Baseline in Nasal Congestion Score at Week 16
The nasal congestion score (NCS) is assessed via a questionnaire where patients are asked Is your nose blocked? with responses ranging from 0 = not at all, to 3=severe. Baseline NCS is defined as the last assessment performed on or before the date of randomization. A negative change from baseline in NCS is considered a favorable outcome.
Time frame: Baseline, Week 16
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fevipiprant 150 mg | Change From Baseline in Nasal Congestion Score at Week 16 | -0.15 score on scale | Standard Error 0.172 |
| Fevipiprant 450 mg | Change From Baseline in Nasal Congestion Score at Week 16 | -0.35 score on scale | Standard Error 0.171 |
| Placebo | Change From Baseline in Nasal Congestion Score at Week 16 | -0.80 score on scale | Standard Error 0.181 |
p-value: 0.07495% CI: [-0.04, 0.94]MMRM
p-value: 0.01295% CI: [0.15, 1.14]MMRM
Secondary
Change From Baseline in Quality of Life as Assessed by the SNOT-22 Questionnaire at Week 16
SNOT-22 (Sino-Nasal Outcome Test) Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been for them over the past 2 weeks on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. Baseline SNOT-22 is defined as the last assessment performed on or before the date of randomization. A negative change from baseline in SNOT-22 is considered a favorable outcome.
Time frame: Baseline, Week 16
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fevipiprant 150 mg | Change From Baseline in Quality of Life as Assessed by the SNOT-22 Questionnaire at Week 16 | -3.23 score on scale | Standard Error 3.349 |
| Fevipiprant 450 mg | Change From Baseline in Quality of Life as Assessed by the SNOT-22 Questionnaire at Week 16 | -10.61 score on scale | Standard Error 3.358 |
| Placebo | Change From Baseline in Quality of Life as Assessed by the SNOT-22 Questionnaire at Week 16 | -8.44 score on scale | Standard Error 3.571 |
p-value: 0.28895% CI: [-4.49, 14.93]MMRM
p-value: 0.66195% CI: [-11.99, 7.65]MMRM
Secondary
Change From Baseline in Sense of Smell as Assessed by the University of Pennsylvania Smell Identification Test (UPSIT) at Week 16
The UPSIT (University of Pennsylvania Smell Identification Test) is a test that measures an individual's ability to detect odors. It consists of 4 workbooks of 10 pages each. On each page there is a different scratch and sniff strip which is embedded with a microencapsulated odorant and a question regarding the smell detected with a four-choice option for the response. The total number of questions in UPSIT is 40. The number of correct responses regarding the smells being experienced is summed to provide a total score that ranges from 0 to 40, with a higher score indicating a better sense of smell. Baseline UPSIT is defined as the last assessment performed on or before the date of randomization. A positive change from baseline in UPSIT is considered a favorable outcome.
Time frame: Baseline, Week 16
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fevipiprant 150 mg | Change From Baseline in Sense of Smell as Assessed by the University of Pennsylvania Smell Identification Test (UPSIT) at Week 16 | 1.05 score on scale | Standard Error 1.242 |
| Fevipiprant 450 mg | Change From Baseline in Sense of Smell as Assessed by the University of Pennsylvania Smell Identification Test (UPSIT) at Week 16 | 4.95 score on scale | Standard Error 1.259 |
| Placebo | Change From Baseline in Sense of Smell as Assessed by the University of Pennsylvania Smell Identification Test (UPSIT) at Week 16 | 0.44 score on scale | Standard Error 1.315 |
p-value: 0.73595% CI: [-2.98, 4.21]MMRM
p-value: 0.01595% CI: [0.89, 8.13]MMRM