A Double-dummy, Double-blind, Randomized, Parallel-group, Active Controlled Study to Evaluate the Efficacy and Safety of QVM149 (Indacaterol Acetate / Glycopyrronium Bromide / Mometasone Furoate) Compared to Salmeterol Xinafoate/Fluticasone Propionate in Children From 12 Years to Less Than 18 Years of Age With Asthma.
Overview
- Phase
- Phase 3
- Intervention
- QVM149
- Conditions
- Asthma
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 304
- Primary Endpoint
- Change from Baseline in Trough FEV1 at Week 26.
- Status
- Not Yet Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
A double-dummy, double-blind, randomized, parallel-group, active controlled study to evaluate the efficacy and safety of QVM149 (indacaterol acetate / glycopyrronium bromide / mometasone furoate) compared to salmeterol xinafoate/fluticasone propionate in children from 12 years to less than 18 years of age with asthma.
Detailed Description
This is a double-dummy, double-blind, randomized, parallel-group, 52 weeks, active controlled study to evaluate the efficacy and safety of indacaterol acetate 150 µg / glycopyrronium bromide 50 µg / mometasone furoate 160 µg (QVM149 150/50/160 µg) od in children from 12 to less than 18 years of age with asthma with pre-bronchodilator FEV1 ≥ 60 % and \< 90 % of the predicted normal value for the participant. The study duration of 60 weeks includes: * a screening period of up to 15 days * a run-in period of 14 days (run-in medication: salmeterol xinafoate/fluticasone propionate 50/250 µg bid) * a treatment period of 52 weeks (either QVM149 150/50/160 µg od and placebo to salmeterol xinafoate/fluticasone propionate 50/500 µg bid, or salmeterol xinafoate/fluticasone propionate 50/500 µg bid and placebo to QVM149 150/50/160 µg od * a safety follow up period of 30 days during which the participant will be back on standard of care treatment as appropriate.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants eligible for inclusion in this study must meet all of the following criteria:
- •Male and female adolescent subjects aged from equal to or greater than 12 years old to less than 18 years old at Screening visit.
- •Written and signed informed consent by parent(s)/legal guardian(s) for the pediatric participant and assent by the pediatric participant (depending on local requirements) must be obtained before any study-specific assessment is performed.
- •Patients with a documented diagnosis of persistent asthma (according to GINA 2022) for a period of at least 1 year prior to Screening.
- •Subjects who have used high dose ICS with LABA in combination for asthma for at least 3 months and at stable doses for at least 1 month prior to Screening.
- •Subjects must be symptomatic / inadequately controlled according to the investigator's opinion despite treatment with high stable doses of ICS with LABA in combination before Screening.
- •A history of one or more documented severe asthma exacerbations within the 12 months prior to Screening that required either:
- •Treatment with systemic corticosteroids (tablets, suspension or injection). OR
- •Hospitalization (defined as an in subject stay or greater than 24-hour stay in an observation area in the emergency room of other equivalent facility). NOTES: Investigators must use appropriate means to ensure the accuracy of the subject's exacerbation history (subject history at Screening documented in source notes, pharmacy records, hospital records, or chart records are acceptable).
- •Subjects must have ACQ-5 score equal to or greater than 1.5 at end of run-in visit prior to randomization (prior to double-blind treatment) and qualify for treatment with high dose LABA/ICS/LAMA.
Exclusion Criteria
- •Participants meeting any of the following criteria are not eligible for inclusion in this study.
- •Subjects who have smoked or inhaled tobacco products within the 6 months period prior to Screening, or who have a smoking history of greater than 10 pack years (Note:1 pack is equivalent to 20 cigarettes. 10 pack years = 1 pack /day x 10 yrs., or ½ pack/day x 20 yrs.) or use of nicotine inhalers such as e-cigarettes at the time of Screening.
- •Subjects who have had an asthma attack/exacerbation requiring systemic steroids OR hospitalization (\> 24 hours) OR emergency room visit (≤ 24 hours) within 6 weeks of Screening. If subjects experience an asthma attack/exacerbation requiring systemic steroids or emergency room visit between Screening and end of Run-in they may be rescreened 6 weeks after recovery from the exacerbation.
- •Subjects who have ever required intubation for a severe asthma attack/exacerbation.
- •Subjects 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.
- •Subjects who have had a respiratory tract infection or asthma worsening as determined by investigator within 4 weeks prior to Screening or between Screening and end of Run-in.
- •Subjects may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
- •Subjects with evidence upon visual inspection (laboratory culture is not required) of clinically significant (in the opinion of investigator) oropharyngeal candidiasis at End of Run-in or earlier, with or without treatment. Subjects may be re-screened once their candidiasis has been treated and has resolved.
- •Subjects with any chronic conditions affecting the upper respiratory tract (eg. Chronic sinusitis) which in the opinion of the investigator may interfere with the study evaluation or optimal participation in the study.
- •Subjects with a history of chronic lung diseases other than asthma, including (but not limited to) sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.
Arms & Interventions
QVM149
QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler® and Placebo to Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler®
Intervention: QVM149
QVM149
QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler® and Placebo to Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler®
Intervention: Placebo to Salmeterol Xinafoate / Fluticasone Propionate
Salmeterol Xinafoate / Fluticasone Propionate Arm
Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler® and Placebo to QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler®.
Intervention: Placebo to QVM149
QVM149
QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler® and Placebo to Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler®
Intervention: Run-In Medication
QVM149
QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler® and Placebo to Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler®
Intervention: Rescue Medication
QVM149
QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler® and Placebo to Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler®
Intervention: Concept 1 Device
QVM149
QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler® and Placebo to Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler®
Intervention: Girohaler
Salmeterol Xinafoate / Fluticasone Propionate Arm
Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler® and Placebo to QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler®.
Intervention: Salmeterol Xinafoate / Fluticasone Propionate
Salmeterol Xinafoate / Fluticasone Propionate Arm
Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler® and Placebo to QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler®.
Intervention: Run-In Medication
Salmeterol Xinafoate / Fluticasone Propionate Arm
Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler® and Placebo to QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler®.
Intervention: Rescue Medication
Salmeterol Xinafoate / Fluticasone Propionate Arm
Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler® and Placebo to QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler®.
Intervention: Concept 1 Device
Salmeterol Xinafoate / Fluticasone Propionate Arm
Salmeterol Xinafoate 50 μg / Fluticasone Propionate 500 μg bid delivered via Girohaler® and Placebo to QVM149 (Indacaterol as acetate 150 µg / glycopyrronium as bromide 50 µg / mometasone furoate 160 µg ) od delivered via Breezhaler®.
Intervention: Girohaler
Outcomes
Primary Outcomes
Change from Baseline in Trough FEV1 at Week 26.
Time Frame: Baseline, Week 26
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.
Secondary Outcomes
- Change from Baseline in Trough FEV1 at Week 52(Baseline, Week 52)
- Change from Baseline in Asthma Control Questionnaire (ACQ-5) score at Week 26 and Week 52(Baseline, Week 26, Week 52)
- Change from Baseline in average Morning and Evening PEFR over 26 weeks and over 52 weeks treatment periods(Baseline, Week 26, Week 52)
- Change from Baseline in average Rescue medication use (daily, daytime, and nighttime) over 26 and 52 week treatment periods(Baseline, Week 26, Week 52)
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose up to 30 days after last dose (up to 56 weeks))
- Change from Baseline in Asthma Quality of Life Questionnaire (AQLQ(S)-12) total score at Week 26 and Week 52(Baseline, Week 26, Week 52)