Systemic Corticosteroids Avoidance Study in Severe Asthma Patients

NCT ID: NCT03629249

Last Updated: 2021-10-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 604 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-13
• Study Completion Date: 2020-02-06

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

QAW039 150 mg

QAW039 150 mg once daily orally

Group Type: EXPERIMENTAL

QAW039 150 mg once daily

Intervention Type: DRUG

QAW039 150 mg once daily (one tablet of blinded QAW039 150 mg to be given together with one tablet blinded placebo to QAW039 450 mg)

QAW039 450 mg

QAW039 450 mg once daily orally

Group Type: EXPERIMENTAL

QAW039 450 mg once daily

Intervention Type: DRUG

QAW039 450 mg once daily (one tablet of blinded QAW039 450 mg to be given together with one tablet blinded placebo to QAW039 150 mg)

Placebo

Placebo to QAW039 once daily orally

Group Type: PLACEBO_COMPARATOR

Placebo once daily

Intervention Type: DRUG

Placebo to QAW039 once daily (one tablet blinded placebo to QAW039 150 mg and one tablet blinded placebo to QAW039 450 mg).

Interventions

Placebo once daily

Placebo to QAW039 once daily (one tablet blinded placebo to QAW039 150 mg and one tablet blinded placebo to QAW039 450 mg).

Intervention Type: DRUG

QAW039 150 mg once daily

QAW039 150 mg once daily (one tablet of blinded QAW039 150 mg to be given together with one tablet blinded placebo to QAW039 450 mg)

Intervention Type: DRUG

QAW039 450 mg once daily

QAW039 450 mg once daily (one tablet of blinded QAW039 450 mg to be given together with one tablet blinded placebo to QAW039 150 mg)

Intervention Type: DRUG

Other Intervention Names

fevipiprant 150 mg; fevipiprant 450 mg

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Newport Beach, California, United States

Novartis Investigative Site

Westminster, California, United States

Novartis Investigative Site

Winter Park, Florida, United States

Novartis Investigative Site

Bangor, Maine, United States

Novartis Investigative Site

Waldorf, Maryland, United States

Novartis Investigative Site

The Bronx, New York, United States

Novartis Investigative Site

Boerne, Texas, United States

Novartis Investigative Site

Dallas, Texas, United States

Novartis Investigative Site

McKinney, Texas, United States

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

Florida, Buenos Aires, Argentina

Novartis Investigative Site

Mar del Plata, Buenos Aires, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Novartis Investigative Site

San Miguel de Tucumán, Tucumán Province, Argentina

Novartis Investigative Site

San Miguel de Tucumán, Tucumán Province, Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

CABA, , Argentina

Novartis Investigative Site

Córdoba, , Argentina

Novartis Investigative Site

Erpent, , Belgium

Novartis Investigative Site

Lebbeke, , Belgium

Novartis Investigative Site

Liège, , Belgium

Novartis Investigative Site

Mechelen, , Belgium

Novartis Investigative Site

Vidin, BGR, Bulgaria

Novartis Investigative Site

Pleven, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Curicó, Maule Region, Chile

Novartis Investigative Site

Santiago, Santiago Metropolitan, Chile

Novartis Investigative Site

Zipaquirá, Cundinamarca, Colombia

Novartis Investigative Site

Bogotá, , Colombia

Novartis Investigative Site

Bogotá, , Colombia

Novartis Investigative Site

Bucaramanga, , Colombia

Novartis Investigative Site

Beroun, Czech Republic, Czechia

Novartis Investigative Site

Prague, Czech Republic, Czechia

Novartis Investigative Site

Teplice, Czech Republic, Czechia

Novartis Investigative Site

Teplice, CZE, Czechia

Novartis Investigative Site

Jindřichův Hradec, , Czechia

Novartis Investigative Site

Lovosice, , Czechia

Novartis Investigative Site

Varnsdorf, , Czechia

Novartis Investigative Site

Montpellier, Herault, France

Novartis Investigative Site

Lyon, Rhone, France

Novartis Investigative Site

Grenoble, , France

Novartis Investigative Site

Pessac, , France

Novartis Investigative Site

Koblenz, North Rhine-Westphalia, Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Darmstadt, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Hamburg, , Germany

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Hamburg, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Landsberg, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Mainz, , Germany

Novartis Investigative Site

Marburg, , Germany

Novartis Investigative Site

Witten, , Germany

Novartis Investigative Site

Heraklion Crete, Greece, Greece

Novartis Investigative Site

Athens, GR, Greece

Novartis Investigative Site

Athens, GR, Greece

Novartis Investigative Site

Thessaloniki, GR, Greece

Novartis Investigative Site

Thessaloniki, GR, Greece

Novartis Investigative Site

Győr, HUN, Hungary

Novartis Investigative Site

Hajdúnánás, HUN, Hungary

Novartis Investigative Site

Kapuvár, HUN, Hungary

Novartis Investigative Site

Püspökladány, HUN, Hungary

Novartis Investigative Site

Százhalombatta, HUN, Hungary

Novartis Investigative Site

Balassagyarmat, , Hungary

Novartis Investigative Site

Gödöllő, , Hungary

Novartis Investigative Site

Nyíregyháza, , Hungary

Novartis Investigative Site

Pécs, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

San Isidro, Lima region, Peru

Novartis Investigative Site

Cusco, , Peru

Novartis Investigative Site

Lima, , Peru

Novartis Investigative Site

Piura, , Peru

Novartis Investigative Site

Lipa City, Batangas, Philippines

Novartis Investigative Site

Iloilo City, Iloilo, Philippines

Novartis Investigative Site

Iloilo City, , Philippines

Novartis Investigative Site

Barnaul, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Petrozavodsk, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Saratov, , Russia

Novartis Investigative Site

Stavropol, , Russia

Novartis Investigative Site

Volgograd, , Russia

Novartis Investigative Site

Bardejov, Slovak Republic, Slovakia

Novartis Investigative Site

Humenné, Slovak Republic, Slovakia

Novartis Investigative Site

Levice, Slovak Republic, Slovakia

Novartis Investigative Site

Spišská Nová Ves, Slovak Republic, Slovakia

Novartis Investigative Site

Žilina, , Slovakia

Novartis Investigative Site

Berea, Durban, South Africa

Novartis Investigative Site

Cape Town, , South Africa

Novartis Investigative Site

Marbella, Andalusia, Spain

Novartis Investigative Site

Badalona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Santiago de Compostela, , Spain

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Mersin, , Turkey (Türkiye)

Novartis Investigative Site

Portsmouth, Hants, United Kingdom

Novartis Investigative Site

Chertsey, Surrey, United Kingdom

Novartis Investigative Site

Bradford, West Yorkshire, United Kingdom

Novartis Investigative Site

Hanoi, , Vietnam

Novartis Investigative Site

Hanoi, , Vietnam

Novartis Investigative Site

Ho Chi Minh City, , Vietnam

Countries

United States; Argentina; Belgium; Bulgaria; Chile; Colombia; Czechia; France; Germany; Greece; Hungary; Peru; Philippines; Russia; Slovakia; South Africa; Spain; Thailand; Turkey (Türkiye); United Kingdom; Vietnam

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=727

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

2018-000212-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CQAW039A2323

Identifier Type: -

Identifier Source: org_study_id