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

Nasal Polyps Clinical Trial

— THUNDER  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03681093
• Other study ID #: CQAW039A2322
• Secondary ID: 2018-002073-22
• Status: Completed
• Phase: Phase 3
• Start date: March 26, 2019
• Est. completion date: June 10, 2020

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: June 10, 2020
• Est. primary completion date: May 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Nasal Polyps
• Polyps

Intervention

Drug:
• Fevipiprant 150 mg
Fevipiprant (QAW039) 150 mg once daily administered orally as tablet
• Fevipiprant 450 mg
Fevipiprant (QAW039) 450 mg once daily administered orally as tablet
• Placebo
Placebo once daily administered orally as tablet

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Florida	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Erpent
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Czechia	Novartis Investigative Site	Kladno
Czechia	Novartis Investigative Site	Olomouc	Czech Republic
Czechia	Novartis Investigative Site	Svitavy	Czech Republic
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Rozzano	MI
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Enschede
Poland	Novartis Investigative Site	Strzelce Opolskie
Poland	Novartis Investigative Site	Zawadzkie
United States	Novartis Investigative Site	Irvine	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Czechia,  Germany,  Italy,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, Week 16
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.	Baseline, Week 16
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.	Baseline, Week 16
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.	Baseline, Week 16

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com