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

• ClinicalTrials.gov Identifier: NCT03158311
• Recruitment Status: Completed
• First Posted: May 18, 2017
• Last Update Posted: September 20, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: QVM149; Drug: Salmeterol/fluticasone plus tiotropium	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1436 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 is open label for which investigators and patients will have full knowledge the patient has been assigned free triple combination comparator treatment. Within the two QVM149 treatment arms patients, investigator staff, and persons performing the assessments, will remain blind to the identity of the actual QVM149 treatment dose but will have full knowledge that the patient has been assigned QVM149 as study treatment. The data analysts and sponsor team will be blinded to Case Report Forms that reveal the treatment arm. Randomization data and treatment codes are kept strictly confidential until the time of unblinding, and will not be 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

Arms and Interventions

Arm	Intervention/treatment
Experimental: QVM149 arm 1; QVM149 150/50/80 μg o.d. delivered via Concept1	Drug: QVM149; Indacaterol acetate / Glycopyrronium bromide / Mometasone furoate
Experimental: QVM149 arm 2; QVM149 150/50/160 μg o.d. delivered via Concept1	Drug: QVM149; Indacaterol acetate / Glycopyrronium bromide / Mometasone furoate
Active Comparator: Salmeterol/fluticasone plus tiotropium arm; Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®	Drug: Salmeterol/fluticasone plus tiotropium; free triple arm of Salmeterol/fluticasone plus tiotropium

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score [ Time Frame: 24 weeks ]
   The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma.

Secondary Outcome Measures :

1. Change from baseline in Trough FEV1 [ Time Frame: 8 weeks, 16 weeks, 24 weeks ]
   Forced Expiratory Volume in 1 second (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.
2. Change from baseline in Asthma Control Questionnaire (ACQ-7) total score [ Time Frame: 16 weeks, 24 weeks ]
   ACQ is the Asthma Control Questionnaire (scoring 5 symptoms, FEV1 entered by the investigator and the rescue medication use entered by the patient) validated to evaluate different levels of asthma control
3. Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score [ Time Frame: 16 weeks ]
   The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma.
4. Percentage of patients achieving the minimal important difference (MCID) change from baseline ACQ-7 ≥ 0.5 decrease [ Time Frame: 16 weeks, 24 weeks ]
   Responder rate; MCID for ACQ-7 is 0.5 decrease.
5. Percentage of patients achieving the minimal important difference (MCID) change from baseline AQLQ ≥ 0.5 increase [ Time Frame: 16 weeks, 24 weeks ]
   Responder rate; MCID for AQLQ is 0.5 increase.
6. Change from baseline in Forced Vital Capacity (FVC) [ Time Frame: 8 weeks, 16 weeks, 24 weeks ]
   FVC is the total amount of air exhaled during the FEV test.
7. Change from baseline in Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity (FEF25-75) [ Time Frame: 8 weeks, 16 weeks, 24 weeks ]
   Forced expiratory flow during the mid (25 - 75%) portion of the FVC.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 have 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 must 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 (see section 6.4.5) which required medical care from a physician, ER 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 demonstrate an increase in FEV1 of ≥ 12% and 200 mL.

Exclusion Criteria:

• Patients who have a smoking history of greater than 20 pack years.
• Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
• Patients who have 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 have 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.

Contacts and Locations

  Show 180 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03158311 History of Changes
• Other Study ID Numbers: CQVM149B2306
• First Posted: May 18, 2017
• Last Update Posted: September 20, 2019
• Last Verified: September 2019

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

QVM149; asthma; adult

Additional relevant MeSH terms:

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