Efficacy study of QVM149 in uncontrolled asthma patients

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2017-000136-34-GR
• Date of registration: 16/02/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: Efficacy study of QVM149 in uncontrolled asthma patients
• Scientific 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
• Date of first enrolment: 16/03/2018
• Target sample size: 1251
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000136-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Partially blind with double blind for QVM149 arms and open-label for comparator arm.; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Chile, China, Colombia, Czech Republic, Egypt, Germany, Greece, Hungary, India, Israel, Italy, Mexico, Peru, Poland, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Taiwan, Turkey, United Kingdom, Vietnam

Contacts

• Name: Veronique Schaaf
• Affiliation: Novartis (Hellas) S.A.C.I.

• Name: Veronique Schaaf
• Affiliation: Novartis (Hellas) S.A.C.I.

Key inclusion & exclusion 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 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 951
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Asthma
MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Indacaterol acetate/Glycopyrronium bromide/mometasone furoate
Product Code: QVM149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: INDACATEROL ACETATE
Other descriptive name: INDACATEROL ACETATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: MOMETASONE FUROATE
Other descriptive name: MOMETASONE FUROATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 80-
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Indacaterol acetate/Glycopyrronium bromide/Mometasone furoate
Product Code: QVM149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: INDACATEROL ACETATE
Other descriptive name: INDACATEROL ACETATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: MOMETASONE FUROATE
Other descriptive name: MOMETASONE FUROATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 160-
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Seretide Accuhaler® (also known as Diskus®)
Product Name: Salmeterol xinofoate/Fluticasone propionate
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: SALMETEROL XINAFOATE
CAS Number: 94749-08-3
Other descriptive name: SALMETEROL XINAFOATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: FLUTICASONE PROPIONATE
CAS Number: 80474-14-2
Other descriptive name: FLUTICASONE PROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Spiriva Respimat®
Product Name: Spiriva Respimat®
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: TIOTRO

Primary Outcome(s)

Main Objective: 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.

Primary end point(s): Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score

Secondary Objective: - To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of Trough FEV1 after 24 weeks of treatment.
- To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of Asthma Quality of Life Questionnaire over 24 weeks of treatment.
- To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of Asthma Control Questionnaire over 24 weeks of treatment.
- To evaluate efficacy of QVM149 high-dose and QVM149 medium-dose compared to salmeterol/ fluticasone + tiotropium in terms of lung function over 24 weeks of treatment.

Timepoint(s) of evaluation of this end point: 24 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - 8 weeks, 16 weeks, 24 weeks
- 16 weeks, 24 weeks
- 16 weeks
- 16 weeks, 24 weeks
- 16 weeks, 24 weeks
- 8 weeks, 16 weeks, 24 weeks
- 8 weeks, 16 weeks, 24 weeks

Secondary end point(s): - Change from baseline in Trough FEV1
- Change from baseline in Asthma Control Questionnaire (ACQ-7) total score
- Change from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score
- Percentage of patients achieving the minimal important difference (MCID) change from baseline ACQ-7 = 0.5 decrease
- Percentage of patients achieving the minimal important difference (MCID) change from baseline AQLQ = 0.5 increase
- Change from baseline in Forced Vital Capacity (FVC)
- Change from baseline in Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity (FEF25-75)

Secondary ID(s)

CQVM149B2306

2017-000136-34-CZ

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date:
Contact: