Study of Efficacy of Fevipiprant in Patients With Nasal Polyposis and Asthma (THUNDER)

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.

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.

Study Overview

• Status: Completed
• Conditions: Nasal Polyps
• Intervention / Treatment: Drug: Fevipiprant 150 mg; Drug: Fevipiprant 450 mg; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABE
    • Novartis Investigative Site
  • Mendoza, Argentina, 5500
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1426ABP
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1425BEN
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1414AIF
      • Novartis Investigative Site
    • Florida, Buenos Aires, Argentina, B1602DQD
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DBS
      • Novartis Investigative Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Erpent, Belgium, 5100
    • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1V 4W2
    • Novartis Investigative Site
  • Ontario
    • Ottawa, Ontario, Canada, K1G 6C6
      • Novartis Investigative Site
• Czechia
  • Kladno, Czechia, 27259
    • Novartis Investigative Site
  • Czech Republic
    • Olomouc, Czech Republic, Czechia, 779 00
      • Novartis Investigative Site
    • Svitavy, Czech Republic, Czechia, 568 25
      • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
• Italy
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands
    • Novartis Investigative Site
  • Enschede, Netherlands, 7511 JH
    • Novartis Investigative Site
• Poland
  • Strzelce Opolskie, Poland, 47 100
    • Novartis Investigative Site
  • Zawadzkie, Poland, 47-120
    • Novartis Investigative Site
• United States
  • California
    • Irvine, California, United States, 92618
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fevipiprant 150 mg; Fevipiprant (QAW039) 150 mg once daily orally	Drug: Fevipiprant 150 mg; Fevipiprant (QAW039) 150 mg once daily administered orally as tablet
Experimental: Fevipiprant 450 mg; Fevipiprant (QAW039) 450 mg once daily orally	Drug: Fevipiprant 450 mg; Fevipiprant (QAW039) 450 mg once daily administered orally as tablet
Placebo Comparator: Placebo; Placebo once daily orally	Drug: Placebo; Placebo once daily administered orally as tablet

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Actual): May 29, 2020
• Study Completion (Actual): June 10, 2020

Study Registration Dates

• First Submitted: September 20, 2018
• First Submitted That Met QC Criteria: September 20, 2018
• First Posted (Actual): September 21, 2018

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Asthma; Bronchial Diseases; Lung Diseases; Nasal Polyposis; QAW039; Respiratory Hypersensitivity; Fevipiprant; Nasal polyp score (NPS); Nasal congestion score (NCS); Nose Diseases
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Nose Diseases; Nasal Polyps; Polyps; Physiological Effects of Drugs; Growth Substances; Plant Growth Regulators; Indoleacetic Acids
• Other Study ID Numbers: CQAW039A2322; 2018-002073-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No