A Multicenter Randomized 52 Week Treatment Double-blind, Triple Dummy Parallel Group Study to Assess the Efficacy and Safety of QMF149 Compared to Mometasone Furoate in Participants With Asthma

Novartis

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Drug: Mometasone furoate; Drug: Salmeterol xinafoate/fluticasone propionate; Drug: Indacaterol acetate/Mometasone furoate

Study type: Interventional

Funder types: Industry

Identifiers

NCT02554786

2015-002529-21 (EudraCT Number)

CQVM149B2301

Details and patient eligibility

About

The purpose of the trial is to evaluate the efficacy and safety of two different doses of QMF149 (QMF149 150/160 µg and QMF149 150/320 µg via Concept1) over two respective MF doses (MF 400 µg and MF 800 µg via Twisthaler® (total daily dose)) in poorly controlled asthmatic participants as determined by pulmonary function testing, and effects on asthma control

Enrollment: 2,216 patients

Sex: All

Ages: 12 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with a diagnosis of asthma, for a period of at least 1 year prior to Visit 1 (Screening)
• Participants who have used medium or high dose inhaled corticosteroids (ICS) or low dose of long acting beta-2 agonist (LABA)/ICS combinations for asthma for at least 3 months and at stable doses for at least 1 month prior to Visit 1
• Participants must have ACQ-7 score ≥ 1.5 at Visit 101 and at Visit 102 (prior to double-blind treatment) and qualify for treatment with medium or high dose LABA/ICS
• Pre-bronchodilator ≥ 50% Forced expiratory volume in 1 second (FEV1) of < 85 % of the predicted normal value for the participants after withholding bronchodilators at both Visit 101 and 102, according to American Thoracic Society/European Respiratory Society (ATS/ERS) criteria.
• Withholding period of bronchodilators prior to spirometry: short acting beta-2 agonist (SABA) for ≥ 6 hours and FDC or free combinations of ICS/LABA for ≥ 48 hours, short acting anticholinergics (SAMA) for ≥ 8 hours, xanthines >=07 days
• A one-time repeat/re-testing of percent predicted FEV1 (prebronchodilator FEV1) is allowed at Visit 101 and at Visit 102.

Spacer devices are permitted for reversibility testing only.

-Participants who demonstrate an increase in FEV1 of 12% and 200 mL within 30 minutes after administration of 400 µg salbutamol/360 µg albuterol (or equivalent dose) at Visit 101 All participants must perform a reversibility test at Visit 101

If reversibility is not demonstrated at Visit 101:

• Reversibility should be repeated once-
• Participants may be permitted to enter the study with historical evidence of reversibility that was performed according to ATS/ERS guidelines within 2 years prior to Visit 1
• Alternatively, participants may be permitted to enter the study with a historical positive bronchoprovocation test that was performed within 2 years prior to Visit 1.

Exclusion criteria

• Participants who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years. This includes use of nicotine inhalers such as e-cigarettes at the time of Visit 1
• Participants who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening)
• Participants who have ever required intubation for a severe asthma attack/exacerbation.
• Participants who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator's medical judgment at risk participating in the study).
• Participants who have had a respiratory tract infection or asthma worsening as determined by the investigator within 4 weeks prior to Visit 1 (Screening) or between Visit 1 and Visit 102. Participants may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
• Participants with a history of chronic lung diseases other than asthma, including (but not limited to) Chronic Obstructive Pulmonary Disease (COPD), sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
• Participants with severe narcolepsy and/or insomnia.
• Participants who have a clinically significant electrocardiogram (ECG) abnormality at Visit 101 (Start of Run- In epoch) and at any time between Visit 101 and Visit 102 (including unscheduled ECG). ECG evidence of myocardial infarction at Visit 101 (via central reader) should be clinically assessed by the investigator with supportivedocumentation
• Participants with a history of hypersensitivity to lactose, any of the study drugs or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof
• Participants who have not achieved an acceptable spirometry results at Visit 101 in accordance with ATS/ERS criteria for acceptability and repeatability (rescreening allowed only once).

Repeat spirometry may be allowed once in an ad-hoc visit if the spirometry did not qualify due to ATS/ERS criteria. If the participant fails the repeat assessment, the participant may be rescreened once

• Participants on Maintenance Immunotherapy (desensitization) for allergies or less than 3 months prior to Visit 101 or participants on Maintenance Immunotherapy for more than 3 months prior to Visit 101 but expected to change throughout the course of the study.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and for 30 days after stopping of study treatment.
• Long acting muscarinic antagonist (LAMA) use within 3 months prior to Visit 101

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,216 participants in 5 patient groups

QMF149 150/160 µg

Experimental group

Description:

QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 μg was delivered once daily (o.d) via Concept1 inhaler in the evening.

Treatment:

Drug: Indacaterol acetate/Mometasone furoate

QMF149 150/320 µg

Experimental group

Description:

QMF149 (Indacaterol acetate/Mometasone furoate) 150/320 μg was delivered o.d via Concept1 inhaler in the evening.

Treatment:

Drug: Indacaterol acetate/Mometasone furoate

MF 400 µg

Active Comparator group

Description:

Mometasone furoate (MF) 400 μg was delivered o.d via Twisthaler® in the evening

Treatment:

Drug: Mometasone furoate

Salmeterol /fluticasone 50/500 μg

Active Comparator group

Description:

Salmeterol xinafoate/fluticasone propionate 50/500 μg was delivered twice daily (in the morning and in the evening) via Accuhaler®.

Treatment:

Drug: Salmeterol xinafoate/fluticasone propionate

MF 800 μg

Active Comparator group

Description:

MF 800 μg of total daily dose (400 μg twice daily, in the morning and in the evening) was delivered via Twisthaler®.

Treatment:

Drug: Mometasone furoate