Study of Efficacy of Fevipiprant in Patients With Nasal Polyposis and Asthma

Study Overview
=================
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.

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of Fevipiprant Once Daily Plus Standard-of-care (SoC) for Assessment of the Efficacy in Reduction of Nasal Polyp Size in Patients With Nasal Polyposis and Concomitant Asthma.

Conditions
-----------------
Nasal Polyps

Intervention / Treatment
-----------------
* Drug: Fevipiprant 150 mg
* Drug: Fevipiprant 450 mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fevipiprant 150 mg<br>Fevipiprant (QAW039) 150 mg once daily orally | Drug: Fevipiprant 150 mg<br>* Fevipiprant (QAW039) 150 mg once daily administered orally as tablet<br>|
| Experimental: Fevipiprant 450 mg<br>Fevipiprant (QAW039) 450 mg once daily orally | Drug: Fevipiprant 450 mg<br>* Fevipiprant (QAW039) 450 mg once daily administered orally as tablet<br>|
| Placebo Comparator: Placebo<br>Placebo once daily orally | Drug: Placebo<br>* Placebo once daily administered orally as tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nasal Polyposis, Asthma, Nasal polyp score (NPS), Nasal congestion score (NCS), Bronchial Diseases, Lung Diseases, Nose Diseases, Respiratory Hypersensitivity, Fevipiprant, QAW039