Clinical trial NCT03629249: Systemic Corticosteroids Avoidance Study in Severe Asthma Patients
Official title: A 52-week, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Placebo-controlled Study of Fevipiprant Once Daily Plus Standard-of-care (SoC) for Reduction of Systemic Corticosteroids (Oral and Parenteral) Use in Patients With Severe Asthma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases
Obstructive Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity
Immune System Diseases
Fevipiprant
QAW039
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 604
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall purpose of this study was to determine the efficacy of fevipiprant (150 mg and 450 mg once daily), compared with placebo, as add-on to standard-of-care asthma therapy, in terms of avoidance of corticosteroid use over 52 weeks.

Detailed description: This was a randomized, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study to determine the ability of fevipiprant (QAW039) plus standard-of-care (SoC) compared with placebo plus SoC to reduce the use of systemic corticosteroids (SCS) in patients with severe asthma. The study included:

* a Screening period of up to 2 weeks to assess eligibility;
* a Run-in period of 4 or 10 weeks to evaluate maintenance of asthma control and to collect baseline safety data. The Run-in period was 4 weeks for patients coming with high-dose ICS/LABA (inhaled corticosteroids/long-acting beta-agonist) and 10 weeks for patients switching from mid-dose to high-dose ICS/LABA as per protocol during the run-in period;
* a Treatment period of 52 weeks. Upon completion of the Run-in period, all patients who met eligibility criteria were randomized to 1 of 3 treatment groups (fevipiprant 150 mg or 450 mg or placebo once daily) in a ratio 1:1:1. Randomized patients were stratified according to their peripheral blood eosinophil count (\< 250 cells/μl or ≥ 250 cells/μl);
* a Follow-up period of 2 weeks following the last dose of study drug to collect additional data for safety variables.

The main purpose of this study was to determine the efficacy of fevipiprant (150 mg and 450 mg once daily), compared with placebo, as add-on to GINA (Global Initiative for Asthma) treatment step 4 or 5 SoC asthma therapy in terms of avoidance of SCS use over 52 weeks in patients with inadequately controlled severe asthma and high eosinophil counts (eosinophil count at Visit 1 ≥250 cells/ μl) and in the overall patient population regardless of eosinophil counts.

On 16-Dec-2019 the sponsor decided to terminate study CQAW039A2323 earlier than the planned study completion. There were no safety findings with fevipiprant that contributed to this decision. The planned treatment period of 52 weeks was not completed by any patient; patients were treated for a median time of 14 weeks in each group and a maximum of up to 36 weeks.

Eligibility criteria: Inclusion Criteria:

* Patients with a diagnosis of asthma for a period of at least 3 months prior to Screening Visit with current asthma severity step 4 or 5 (GINA 2018)
* Currently on treatment with medium or high dose ICS/LABA +/- other controller (i.e.long-acting muscarinic antagonist (LAMA), leukotriene receptor antagonist (LTRA) etc. as per GINA) for a minimum of 6 weeks prior to Screening Visit
* At screening, patients with FEV1 of ≤80% of the predicted normal value for the patient, after withholding bronchodilators at Screening Visit and beginning of Run-In Visit
* An increase of ≥12% and ≥200 ml in FEV1 approximately 10 to 15 minutes after administration of 400 mcg of salbutamol/albuterol prior to randomization (documented historical reversibility was accepted).
* Demonstration of inadequate control of asthma based on an ACQ-5 score ≥1.5 at Screening Visit and Treatment Day 1 Visit
* Documented history of at least 1 asthma exacerbation within 1 year prior to enrollment

Exclusion Criteria:

* Asthma exacerbation, within 6 weeks prior to enrollment (screening) that required SCS, hospitalization, or emergency room visit
* Chronic/maintenance use of oral corticosteroids (OCS) for asthma (total OCS use days greater than 6 months; continuously or intermittently) within the last year
* Prior use of biologics that has potential to interfere/ affect asthma disease progression, in the previous 6 months from run-in period.
* Any contraindications of SCS use e.g. diabetes, narrow angle glaucoma, or any other as defined by the treating physician
* Pregnant or nursing (lactating) women
* Use of other investigational drugs within 5 half-lives of enrollment, or \[within 30 days\], whichever is longer

Primary outcomes:
measure: Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Overall Population
timeFrame: 52 weeks
measure: Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Subpopulation of Patients With High Eosinophil Count (≥ 250 Cells/µl)
timeFrame: 52 weeks
Secondary outcomes:
measure: Change From Baseline in Daytime Symptom Scores
timeFrame: Baseline, up to Week 29-32
measure: Change From Baseline in Nighttime Symptom Scores
timeFrame: Baseline, up to Week 29-32
measure: Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit
timeFrame: Baseline, up to Week 28
measure: Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit
timeFrame: Baseline, up to Week 28
measure: Percentage of Patients Requiring ≥ 7.5 mg Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Per Day Continuously for at Least 30 Days
timeFrame: Up to 36 weeks
measure: Percentage of Patients With no Systemic Corticosteroids Use
timeFrame: Week 36
measure: Percentage of Patients With Prescription of Biologic Therapy
timeFrame: Up to 36 weeks
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Westminster
country: United States
facility: Novartis Investigative Site
state: California
city: Winter Park
country: United States
facility: Novartis Investigative Site
state: Florida
city: Bangor
country: United States
facility: Novartis Investigative Site
state: Maine
city: Waldorf
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Bronx
country: United States
facility: Novartis Investigative Site
state: New York
city: Boerne
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: McKinney
country: United States
facility: Novartis Investigative Site
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Florida
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Erpent
country: Belgium
facility: Novartis Investigative Site
city: Lebbeke
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Mechelen
country: Belgium
facility: Novartis Investigative Site
city: Vidin
country: Bulgaria
facility: Novartis Investigative Site
state: BGR
city: Pleven
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: Region Metropolitana
city: Curico
country: Chile
facility: Novartis Investigative Site
state: VII Region Del Maule
city: Zipaquira
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
city: Beroun
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Teplice
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Teplice
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Jindrichuv Hradec
country: Czechia
facility: Novartis Investigative Site
city: Lovosice
country: Czechia
facility: Novartis Investigative Site
city: Varnsdorf
country: Czechia
facility: Novartis Investigative Site
city: Montpellier cedex 5
country: France
facility: Novartis Investigative Site
state: Herault
city: Lyon cedex 04
country: France
facility: Novartis Investigative Site
state: Rhone
city: Grenoble Cedex 9
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: Koblenz
country: Germany
facility: Novartis Investigative Site
state: NRW
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Darmstadt
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Landsberg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Witten
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Gyor
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Hajdunanas
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Kapuvár
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Puspokladany
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Szazhalombatta
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Balassagyarmat
country: Hungary
facility: Novartis Investigative Site
city: Godollo
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyhaza
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: San Isidro
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Cusco
country: Peru
facility: Novartis Investigative Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Piura
country: Peru
facility: Novartis Investigative Site
city: Lipa City
country: Philippines
facility: Novartis Investigative Site
state: Batangas
city: Iloilo city
country: Philippines
facility: Novartis Investigative Site
state: Iloilo
city: Iloilo City
country: Philippines
facility: Novartis Investigative Site
city: Iloilo
country: Philippines
facility: Novartis Investigative Site
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Petrozavodsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saratov
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Stavropol
country: Russian Federation
facility: Novartis Investigative Site
city: Volgograd
country: Russian Federation
facility: Novartis Investigative Site
city: Bardejov
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Humenne
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Levice
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Spisska Nova Ves
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Zilina
country: Slovakia
facility: Novartis Investigative Site
city: Berea
country: South Africa
facility: Novartis Investigative Site
state: Durban
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Marbella
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Portsmouth
country: United Kingdom
facility: Novartis Investigative Site
state: Hants
city: Chertsey
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
References: