AsthmaPhase 3ARGONNCT03158311
Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium
A Phase 3 study testing QVM149 and Salmeterol/fluticasone plus tiotropium in people with Asthma, run by Novartis Pharmaceuticals at 163 sites in 20 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- QVM149 and Salmeterol/fluticasone plus tiotropium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,426 participants
- Where
- 163 sitesin 20 countries
- Study dates
- 5 Feb 2018to 19 Jul 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
163 sites in 20 countries.
163 sites in 20 countries
Germany41 sites
Novartis Investigative Site
Berlin, 10119
Novartis Investigative Site
Berlin, 10625
Novartis Investigative Site
Berlin, 10717
Novartis Investigative Site
Berlin, 10969
Novartis Investigative Site
Berlin, 12157
Novartis Investigative Site
Berlin, 12159
Novartis Investigative Site
Berlin, 12203
Novartis Investigative Site
Berlin, 13086
Novartis Investigative Site
Berlin, 13156
Novartis Investigative Site
Berlin, 13187
Novartis Investigative Site
Berlin, 14050
Novartis Investigative Site
Böhlen, 04564
Novartis Investigative Site
Bonn, 53123
Novartis Investigative Site
Darmstadt, 64283
Novartis Investigative Site
Dortmund, 44263
Novartis Investigative Site
Einbeck, 37574
Novartis Investigative Site
Frankfurt, 60389
Novartis Investigative Site
Frankfurt, 60596
Novartis Investigative Site
Fürstenwalde, 15517
Novartis Investigative Site
Geesthacht, Schleswig-Holstein, 12502
Novartis Investigative Site
Gelsenkirchen, 45879
Novartis Investigative Site
Hamburg, 20354
Novartis Investigative Site
Hamburg, 22335
Novartis Investigative Site
Hanover, 30167
Novartis Investigative Site
Hanover, 30173
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Leipzig, 04157
Novartis Investigative Site
Leipzig, 04275
Novartis Investigative Site
Leipzig, 04357
Novartis Investigative Site
Lübeck, 23552
Novartis Investigative Site
Ludwigsburg, 71640
Novartis Investigative Site
Marburg, 35037
Novartis Investigative Site
Marburg, D-35037
Novartis Investigative Site
Menden, 58706
Novartis Investigative Site
Mittweida, 09648
Novartis Investigative Site
München, 81241
Novartis Investigative Site
Peine, Lower Saxony, 31224
Novartis Investigative Site
Potsdam, 14467
Novartis Investigative Site
Rüdersdorf, 15562
Novartis Investigative Site
Schleswig, 24837
Novartis Investigative Site
Witten, 58452
Argentina28 sites
Novartis Investigative Site
Bahía Blanca, B8000JRB
Novartis Investigative Site
Berazategui, Buenos Aires, 1888
Novartis Investigative Site
Buenos Aires, Nueve De Julio, B6500BWQ
Novartis Investigative Site
Buenos Aires, 1900
Novartis Investigative Site
Buenos Aires, B1646EBJ
Novartis Investigative Site
Buenos Aires, C1125ABE
Novartis Investigative Site
Buenos Aires, C1425FVH
Novartis Investigative Site
Caba, Buenos Aires, C1280AEB
Novartis Investigative Site
CABA, Buenos Aires, C1122AAK
Novartis Investigative Site
CABA, Buenos Aires, C1414AIF
Novartis Investigative Site
CABA, Buenos Aires, C1424BSF
Novartis Investigative Site
CABA, Buenos Aires, C1425BEN
Novartis Investigative Site
Ciudad Autonoma de Bs As, C1128AAF
Novartis Investigative Site
Concepción del Uruguay, Entre Ríos Province, 3260
Novartis Investigative Site
Florida, Buenos Aires, B1602DQD
Novartis Investigative Site
Lanus, Buenos Aires, B8000XAV
Novartis Investigative Site
Mar del Plata, Buenos Aires, 7600
Novartis Investigative Site
Mendoza, 5500
Novartis Investigative Site
Mendoza, 5501
Novartis Investigative Site
Mendoza, M5500CBA
Novartis Investigative Site
Nueve de Julio, Buenos Aires, B6500EZL
Novartis Investigative Site
Ranelagh, Partido de Berazate, Buenos Aires, 1884
Novartis Investigative Site
Rosario, Santa Fe Province, S2000AII
Novartis Investigative Site
Rosario, Santa Fe Province, S2000BRH
Novartis Investigative Site
Salta, 4400
Novartis Investigative Site
San Miguel de Tucumán, Tucumán Province, 4000
Novartis Investigative Site
Santa Fe, S3000FIL
Novartis Investigative Site
Santa Rosa, La Pampa Province, 6300
Russia18 sites
Novartis Investigative Site
Izhevsk, 426061
Novartis Investigative Site
Kemerovo, 650002
Novartis Investigative Site
Moscow, 105275
Novartis Investigative Site
Moscow, 109544
Novartis Investigative Site
Moscow, 123423
Novartis Investigative Site
Nizhny Novgorod, 603018
Novartis Investigative Site
Novosibirsk, 630102
Novartis Investigative Site
Saint Petersburg, 107022
Novartis Investigative Site
Saint Petersburg, 191186
Novartis Investigative Site
Saint Petersburg, 193312
Novartis Investigative Site
Saint Petersburg, 194354
Novartis Investigative Site
Saint Petersburg, 195271
Novartis Investigative Site
Saint Petersburg, 196143
Novartis Investigative Site
Saint Petersburg, 197022
Novartis Investigative Site
Saratov, 410028
Novartis Investigative Site
Saratov, 410054
Novartis Investigative Site
Ulyanovsk, 432063
Novartis Investigative Site
Yekaterinburg, 620109
India9 sites
Novartis Investigative Site
Coimbatore, Tamil Nadu, 641 045
Novartis Investigative Site
Hyderabad, Telangana, 500 038
Novartis Investigative Site
Kolkata, West Bengal, 700 107
Novartis Investigative Site
Kozhikode, Kerala, 673008
Novartis Investigative Site
Mohali, Punjab, 160 062
Novartis Investigative Site
Nagpur, Maharashtra, 440019
Novartis Investigative Site
Pune, Maharashtra, 411014
Novartis Investigative Site
Vellore, Tamil Nadu, 632004
Novartis Investigative Site
Vijayawada, Andhra Pradesh, 520008
Hungary8 sites
Novartis Investigative Site
Balassagyarmat, 2660
Novartis Investigative Site
Gödöllő, 2100
Novartis Investigative Site
Komló, 7300
Novartis Investigative Site
Püspökladány, HUN, 4150
Novartis Investigative Site
Sellye, 7960
Novartis Investigative Site
Siófok, 8600
Novartis Investigative Site
Szarvas, 5540
Novartis Investigative Site
Szeged, 6722
Slovakia6 sites
Novartis Investigative Site
Bojnice, Slovak Republic, 972 01
Novartis Investigative Site
Humenné, Slovak Republic, 066 01
Novartis Investigative Site
Liptovský Hrádok, Slovak Republic, 033 01
Novartis Investigative Site
Liptovský Mikuláš, 031 23
Novartis Investigative Site
Topoľčany, 95501
Novartis Investigative Site
Žilina, 01001
South Africa6 sites
Novartis Investigative Site
Berea, Durban, 4001
Novartis Investigative Site
Cape Town, 7530
Novartis Investigative Site
Cape Town, 7700
Novartis Investigative Site
Chatsworth, 4092
Novartis Investigative Site
Kempton Park, 1619
Novartis Investigative Site
Pretoria, 0183
Czechia5 sites
Novartis Investigative Site
Lovosice, 41002
Novartis Investigative Site
Miroslav, 67172
Novartis Investigative Site
Ostrava Poruba, Czech Republic, 708 68
Novartis Investigative Site
Prague, Czech Republic, 169 00
Novartis Investigative Site
Teplice, CZE, 415 01
Greece5 sites
Novartis Investigative Site
Athens, GR, 115 27
Novartis Investigative Site
Athens, 12462
Novartis Investigative Site
Thessaloniki, GR, 546 03
Novartis Investigative Site
Thessaloniki, GR, 564 29
Novartis Investigative Site
Thessaloniki, GR, 570 10
Spain5 sites
Novartis Investigative Site
Alzira, Valencia, 46600
Novartis Investigative Site
Benalmádena, Malaga, 29639
Novartis Investigative Site
Cáceres, Extremadura, 10003
Novartis Investigative Site
Esparraguera, Barcelona, 08292
Novartis Investigative Site
Hostalets de Balenya, Catalonia, 08550
Israel4 sites
Novartis Investigative Site
Jerusalem, 91031
Novartis Investigative Site
Jerusalem, 91120
Novartis Investigative Site
Ramat Gan, 5266202
Novartis Investigative Site
Rehovot, 76100
Peru4 sites
Novartis Investigative Site
Cusco, 84
Novartis Investigative Site
Lima, 1
Novartis Investigative Site
San Martín de Porres, Lima region, 31
Novartis Investigative Site
Santiago de Surco, Lima region, 33
Poland4 sites
Novartis Investigative Site
Katowice, 40-648
Novartis Investigative Site
Poznan, 60 823
Novartis Investigative Site
Poznan, 60-214
Novartis Investigative Site
Poznan, 60-693
Serbia4 sites
Novartis Investigative Site
Belgrade, 11000
Novartis Investigative Site
Kamenitz, 21204
Novartis Investigative Site
Kragujevac, 34000
Novartis Investigative Site
Niš, 18000
Mexico3 sites
Novartis Investigative Site
Guadalajara, Jalisco, 44100
Novartis Investigative Site
Guadalajara, Jalisco, 44160
Novartis Investigative Site
Mexico City, Mexico City, 14050
Taiwan3 sites
Novartis Investigative Site
Kaoshiung, Taiwan, 80756
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taipei, 10449
Turkey (Türkiye)3 sites
Novartis Investigative Site
Izmir, 35040
Novartis Investigative Site
Mersin, 33343
Novartis Investigative Site
Yenisehir/Izmir, 35110
Vietnam3 sites
Novartis Investigative Site
Hanoi, 100000
Novartis Investigative Site
Ho Chi Minh City, VNM, 700000
Novartis Investigative Site
Ho Chi Minh City, 700000
Chile2 sites
Novartis Investigative Site
Curicó, Maule Region, 3341643
Novartis Investigative Site
Santiago, Santiago Metropolitan, 7500692
Colombia2 sites
Novartis Investigative Site
Bogota, Cundinamarca, 110911
Novartis Investigative Site
Bogotá, 110221
About this study
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
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.
Read the detailed 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.
- Conditions
- Asthma
- Being tested
- QVM149, Salmeterol/fluticasone plus tiotropium
- Keywords
- QVM149, Asthma, Moderate Asthma, Severe Asthma, ICS/LABA/LAMA, ICS/LABA, LAMA, Adult
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QVM149Drug
Indacaterol acetate / glycopyrronium bromide / mometasone furoate
Salmeterol/fluticasone plus tiotropiumDrug
Free triple arm of salmeterol / fluticasone plus tiotropium
| Study group | Role | What they receive |
|---|---|---|
| QVM149 150/50/80 μg | Experimental | QVM149 150/50/80 μg o.d. delivered via Concept1 Receives: Drug: QVM149 |
| QVM149 150/50/160 μg | Experimental | QVM149 150/50/160 μg o.d. delivered via Concept1 Receives: Drug: QVM149 |
| Salmeterol/fluticasone 50/500 μg plus tiotropium 5 μg | Active comparator | Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat® Receives: Drug: Salmeterol/fluticasone plus tiotropium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 24
Secondary outcomes (7)
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.
Measured: Baseline, Week 8, Week 16 and Week 24
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.
Measured: Baseline, Week 16 and Week 24
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.
Measured: Baseline and Week 16
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.
Measured: Baseline and Week 24
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.
Measured: Baseline and Week 24
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.
Measured: Baseline, Week 8, Week 16 and Week 24
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.
Measured: Baseline, Week 8, Week 16 and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2017
- Study start5 Feb 2018
- Primary completion12 Jul 2019
- Study completion19 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,426 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03158311
- Sponsor's protocol ID
- CQVM149B2306
- Other IDs
- 2017-000136-34, 2017
- Acronym
- ARGON
- Status last verified
- Oct 2021
- First submitted
- 16 May 2017
- Last updated
- 8 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.
PubMed 36472162
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03158311
- Acronym / sponsor ID
- ARGON / CQVM149B2306
- Conditions
- Asthma
- Keywords
- QVM149, Asthma, Moderate Asthma, Severe Asthma, ICS/LABA/LAMA, ICS/LABA, LAMA, Adult
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,426 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 5 Feb 2018 (actual)
- Primary completion
- 12 Jul 2019 (actual)
- Study completion
- 19 Jul 2019 (actual)
- First posted
- 18 May 2017 (actual)
- Results
- Posted 14 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| QVM149 150/50/80 μg | Experimental | Drug: QVM149QVM149 150/50/80 μg o.d. delivered via Concept1 |
| QVM149 150/50/160 μg | Experimental | Drug: QVM149QVM149 150/50/160 μg o.d. delivered via Concept1 |
| Salmeterol/fluticasone 50/500 μg plus tiotropium 5 μg | Active comparator | Drug: Salmeterol/fluticasone plus tiotropiumSalmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat® |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QVM149Indacaterol acetate / glycopyrronium bromide / mometasone furoate | Drug | QVM149 150/50/160 μg, QVM149 150/50/80 μg |
| Salmeterol/fluticasone plus tiotropiumFree triple arm of salmeterol / fluticasone plus tiotropium | Drug | Salmeterol/fluticasone 50/500 μg plus tiotropium 5 μg |
Primary outcome
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score
Time frame: Baseline and Week 24
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.
7 secondary outcomes
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline, Week 8, Week 16 and Week 24
Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score
Time frame: Baseline, Week 16 and Week 24
Change From Baseline in AQLQ Total Score
Time frame: Baseline and Week 16
Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5
Time frame: Baseline and Week 24
Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5
Time frame: Baseline and Week 24
Change From Baseline in Forced Vital Capacity (FVC)
Time frame: Baseline, Week 8, Week 16 and Week 24
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75)
Time frame: Baseline, Week 8, Week 16 and Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36472162Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
163 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing QVM149 and Salmeterol/fluticasone plus tiotropium in people with Asthma, run by Novartis Pharmaceuticals at 163 sites in 20 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 163 sites in Germany, Argentina, Russia, India, Hungary and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score (time frame: Baseline and Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03158311, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.