Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON)
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| ClinicalTrials.gov Identifier: NCT03158311 |
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Recruitment Status :
Completed
First Posted : May 18, 2017
Results First Posted : October 14, 2020
Last Update Posted : October 8, 2021
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Asthma | Drug: QVM149 Drug: Salmeterol/fluticasone plus tiotropium | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1426 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Masking Description: | The free triple combination of salmeterol/fluticasone + tiotropium was open label, for which investigators and patients had full knowledge that the patient had been assigned free triple combination comparator treatment. Within the two QVM149 treatment arms patients, investigator staff, and persons performing the assessments, remained blind to the identity of the actual QVM149 treatment dose but had full knowledge that the patient had been assigned QVM149 as study treatment. The data analysts and sponsor team were blinded to Case Report Forms that reveal the treatment arm. Randomization data and treatment codes were kept strictly confidential until the time of unblinding, and was not accessible by anyone else involved in the study. |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | February 5, 2018 |
| Actual Primary Completion Date : | July 12, 2019 |
| Actual Study Completion Date : | July 19, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: QVM149 150/50/80 μg
QVM149 150/50/80 μg o.d. delivered via Concept1
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Drug: QVM149
Indacaterol acetate / glycopyrronium bromide / mometasone furoate |
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Experimental: QVM149 150/50/160 μg
QVM149 150/50/160 μg o.d. delivered via Concept1
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Drug: QVM149
Indacaterol acetate / glycopyrronium bromide / mometasone furoate |
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Active Comparator: Salmeterol/fluticasone 50/500 μg plus tiotropium 5 μg
Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
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Drug: Salmeterol/fluticasone plus tiotropium
Free triple arm of salmeterol / fluticasone plus tiotropium |
- 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.
- Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline, Week 8, Week 16 and Week 24 ]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.
- Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score [ Time Frame: Baseline, Week 16 and Week 24 ]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.
- Change From Baseline in AQLQ Total Score [ Time Frame: Baseline and Week 16 ]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.
- Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5 [ Time Frame: Baseline and Week 24 ]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.
- Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5 [ 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 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.
- Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline, Week 8, Week 16 and Week 24 ]FVC is the total volume of air exhaled during a expiratory maneuvre. It was assessed by performing a spirometry assessment.
- 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 ]Forced expiratory flow during the mid (25 - 75%) portion of the FVC. It was assessed by performing spirometric assessment.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03158311
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| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Documents provided by Novartis ( Novartis Pharmaceuticals ):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03158311 |
| Other Study ID Numbers: |
CQVM149B2306 2017-000136-34 ( EudraCT Number ) |
| First Posted: | May 18, 2017 Key Record Dates |
| Results First Posted: | October 14, 2020 |
| Last Update Posted: | October 8, 2021 |
| Last Verified: | October 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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QVM149 Asthma Moderate Asthma Severe Asthma |
ICS/LABA/LAMA ICS/LABA LAMA Adult |
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Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Fluticasone Tiotropium Bromide Salmeterol Xinafoate Anti-Inflammatory Agents Bronchodilator Agents Autonomic Agents |
Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Dermatologic Agents Anti-Allergic Agents Parasympatholytics Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents |