Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium

Asthma Clinical Trial

— ARGON  

Official title:

A Multicenter, Partially-Blinded, Randomized, 24-Week, Parallel-Group, Non-Inferiority, Open-Label Active Controlled Study to Compare the Efficacy and Safety of QVM149 With a Free Triple Combination of Salmeterol/Fluticasone + Tiotropium in Patients With Uncontrolled Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03158311
• Other study ID #: CQVM149B2306
• Secondary ID: 2017-000136-34
• Status: Completed
• Phase: Phase 3
• Start date: February 5, 2018
• Est. completion date: July 19, 2019

Study information

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

Clinical Trial Summary

The purpose of this trial was to demonstrate that the efficacy of two treatment arms of the fixed-dose combination product QVM149 was non-inferior to the efficacy of the free combination arm of salmeterol/ fluticasone+ tiotropium in uncontrolled moderate to severe asthmatic patients.

The planned duration of treatment in this study was 24 weeks, followed up by a 7-day follow-up period.

Description:

This study used a randomized, partially-blinded, 24-week, parallel-group, non-inferiority, open-label active controlled design. The study was partially open-label. Investigators and patients had knowledge of treatment allocation between QVM149 and/or comparator, however the QVM149 strength allocation was masked. The global sponsor team responsible for data review and analysis was blinded to all treatment allocations The study consisted of a screening period of up to 1-week, run-in period of 2-weeks, randomized treatment period of 24-weeks, and a follow-up period of 1-week.

At the screening visit, informed consent was obtained, and current and prohibited medications were reviewed. Rescue medication was provided to all patients who met the eligibility criteria and was to be used on an "as needed" basis throughout the study.

At the run-in visit, inclusion and exclusion criteria were reviewed and the patients were supplied with open-label long acting β2-adrenergic agonist/inhaled corticosteroids (LABA/ICS) salmeterol/fluticasone 50/250 μg b.i.d or 50/500 μg b.i.d to match their ICS background medication dose to be stopped at randomization visit.

All patients who met the eligibility criteria were randomized to 1 of 3 treatment arms with a randomization ratio of 1:1:1. The patients were stratified at randomization according to the ICS dose component of background ICS/LABA (medium or high dose) and region.

Treatment period visits were scheduled every 8 weeks. The study used two doses of QVM149 (high dose [150/50/160 μg] and a medium dose [150/50/80 μg] o.d. delivered via Concept1 inhaler) and a comparator treatment (salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d delivered via Respimat®).

All randomized patients were contacted (by telephone) 7 days following the last dose of study medication or last visit, whichever was later, for Safety Follow-up visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1426
• Est. completion date: July 19, 2019
• Est. primary completion date: July 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of asthma for a period of at least 6 months prior to Visit 1 with current asthma severity = step 4 (GINA 2017).

• Patients who had used ICS/LABA combinations for asthma for at least 3 months and at stable medium or high dose of ICS/LABA for at least 1 month prior to Visit 1.

• Patients were required to be symptomatic at screening despite treatment with medium or high stable doses of ICS/LABA as defined by ACQ-7 score = 1.5 at visits 101 and 201 (randomization visit).

• Patients with history of at least one severe asthma exacerbation which required medical care from a physician, emergency room visit (or local equivalent structure) or hospitalization in the 12 months prior to Visit 1 and required systemic corticosteroid treatment for at least 3 days including physician guided self-management treatment with oral corticosteroids as part of written asthma action plan.

• Pre-bronchodilator FEV1 of < 85 % of the predicted normal value for the patient after withholding bronchodilators prior to spirometry at both Visit 101 and Visit 201.

• Patients who demonstrated an increase in FEV1 of = 12% and 200 ml.

Exclusion Criteria:

• Patients who had a smoking history of greater than 20 pack years.

• Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD).

• Patients who had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening).

• Patients treated with a LAMA for asthma within 3 months prior to Visit 1.

• Patients who had a respiratory tract infection or clinical significant asthma worsening as defined by Investigator within 4 weeks prior to Visit 1 or between Visit 1 and Visit 201.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• QVM149
Indacaterol acetate / glycopyrronium bromide / mometasone furoate
• Salmeterol/fluticasone plus tiotropium
Free triple arm of salmeterol / fluticasone plus tiotropium

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Bahia Blanca
Argentina	Novartis Investigative Site	Berazategui	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	Buenos Aires	Nueve De Julio
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	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As
Argentina	Novartis Investigative Site	Concepcion del Uruguay	Entre Rios
Argentina	Novartis Investigative Site	Florida	Buenos Aires
Argentina	Novartis Investigative Site	Lanus	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Nueve de Julio	Buenos Aires
Argentina	Novartis Investigative Site	Ranelagh, Partido De Berazate	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Salta
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Santa Rosa	La Pampa
Chile	Novartis Investigative Site	Curico	VII Region Del Maule
Chile	Novartis Investigative Site	Santiago	Region Metropolitana
Colombia	Novartis Investigative Site	Bogota	Cundinamarca
Colombia	Novartis Investigative Site	Bogota
Czechia	Novartis Investigative Site	Lovosice
Czechia	Novartis Investigative Site	Miroslav
Czechia	Novartis Investigative Site	Ostrava Poruba	Czech Republic
Czechia	Novartis Investigative Site	Prague	Czech Republic
Czechia	Novartis Investigative Site	Teplice	CZE
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	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	Boehlen
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Einbeck
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Furstenwalde
Germany	Novartis Investigative Site	Geesthacht	Schleswig Holstein
Germany	Novartis Investigative Site	Gelsenkirchen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Ludwigsburg
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Menden
Germany	Novartis Investigative Site	Mittweida
Germany	Novartis Investigative Site	Munchen
Germany	Novartis Investigative Site	Peine	Niedersachsen
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Rudersdorf
Germany	Novartis Investigative Site	Schleswig
Germany	Novartis Investigative Site	Witten
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
Greece	Novartis Investigative Site	Thessaloniki	GR
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Balassagyarmat
Hungary	Novartis Investigative Site	Godollo
Hungary	Novartis Investigative Site	Komlo
Hungary	Novartis Investigative Site	Puspokladany	HUN
Hungary	Novartis Investigative Site	Sellye
Hungary	Novartis Investigative Site	Siofok
Hungary	Novartis Investigative Site	Szarvas
Hungary	Novartis Investigative Site	Szeged
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Kozhikode	Kerala
India	Novartis Investigative Site	Mohali	Punjab
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Vellore	Tamil Nadu
India	Novartis Investigative Site	Vijayawada	Andhra Pradesh
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Rehovot
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Peru	Novartis Investigative Site	Cusco
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	San Martin de Porres	Lima
Peru	Novartis Investigative Site	Santiago de Surco	Lima
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Russian Federation	Novartis Investigative Site	Izhevsk
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Ulyanovsk
Russian Federation	Novartis Investigative Site	Yekaterinburg
Serbia	Novartis Investigative Site	Belgrade
Serbia	Novartis Investigative Site	Kragujevac
Serbia	Novartis Investigative Site	Nis
Serbia	Novartis Investigative Site	Sremska Kamenica
Slovakia	Novartis Investigative Site	Bojnice	Slovak Republic
Slovakia	Novartis Investigative Site	Humenne	Slovak Republic
Slovakia	Novartis Investigative Site	Liptovsky Hradok	Slovak Republic
Slovakia	Novartis Investigative Site	Liptovsky Mikulas
Slovakia	Novartis Investigative Site	Topolcany
Slovakia	Novartis Investigative Site	Zilina
South Africa	Novartis Investigative Site	Berea	Durban
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Chatsworth
South Africa	Novartis Investigative Site	Kempton Park
South Africa	Novartis Investigative Site	Pretoria
Spain	Novartis Investigative Site	Alzira	Comunidad Valenciana
Spain	Novartis Investigative Site	Benalmadena	Malaga
Spain	Novartis Investigative Site	Caceres	Extremadura
Spain	Novartis Investigative Site	Esparraguera	Barcelona
Spain	Novartis Investigative Site	Hostalets De Balenya	Cataluna
Taiwan	Novartis Investigative Site	Kaoshiung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Yenisehir/Izmir
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh
Vietnam	Novartis Investigative Site	Ho Chi Minh	VNM

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Chile,  Colombia,  Czechia,  Germany,  Greece,  Hungary,  India,  Israel,  Mexico,  Peru,  Poland,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Taiwan,  Turkey,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score	The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional funtion, and emotional stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life.	Baseline and Week 24
Secondary	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Trough FEV1 is the mean of two FEV1 values measures taken 15 minutes (min) and 45 min prior to evening dose.	Baseline, Week 8, Week 16 and Week 24
Secondary	Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score	The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. Higher score indicates worst symptoms. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.	Baseline, Week 16 and Week 24
Secondary	Change From Baseline in AQLQ Total Score	The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life.	Baseline and Week 16
Secondary	Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 = 0.5	The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. Higher score indicates worst symptoms. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. Decrease of ACQ-7 score of at least 0.5 from baseline was considered clinically meaningful.	Baseline and Week 24
Secondary	Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ = 0.5	The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life. An improvement of 0.5 points in AQLQ score is considered to be the minimally clinically important difference in asthma.	Baseline and Week 24
Secondary	Change From Baseline in Forced Vital Capacity (FVC)	FVC is the total volume of air exhaled during a expiratory maneuvre. It was assessed by performing a spirometry assessment.	Baseline, Week 8, Week 16 and Week 24
Secondary	Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75)	Forced expiratory flow during the mid (25 - 75%) portion of the FVC. It was assessed by performing spirometric assessment.	Baseline, Week 8, Week 16 and Week 24

External Links

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