Randomized crossover trial of QVM149 (indacaterol acetate/glycopyrronium bromide/mometasone furoate) versus salmeterol/fluticasone in 12‑17‑year‑olds with asthma

The primary objective is to demonstrate the superiority of QVM149 150/50/160 µg once daily versus salmeterol 50 µg/fluticasone 500 µg twice daily in trough FEV1 measured at Week 12 of each treatment period in adolescents with asthma. Secondary objectives address efficacy and safety. Efficacy endpoints include:

• change in Asthma Control Questionnaire (ACQ‑5) score at Week 12,
• change in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) score at Week 12,
• total rescue medication use over the 12‑week treatment period,
• rate of asthma exacerbations during the 12‑week period.

Forty adolescents (both male and female) aged 12 to < 18 years with a documented diagnosis of persistent asthma for at least one year were enrolled. Participants were required to have been on a stable medium‑ or high‑dose inhaled corticosteroid/long‑acting β‑agonist (ICS/LABA) regimen for a minimum of three months, with stable dosing for at least one month prior to screening. Eligibility required symptomatic or inadequately controlled disease despite current therapy, an ACQ‑5 score of ≥ 1.5, and a pre‑bronchodilator FEV1 of ≥ 50 % predicted. A history of at least one severe exacerbation requiring systemic corticosteroids or hospitalization within the previous 12 months was mandatory. Subjects demonstrated ≥ 70 % adherence to both inhaler use and electronic diary completion during a run‑in period, and acceptable inhaler technique and spirometry performance were confirmed. Reversibility of ≥ 12 % in FEV1 after short‑acting bronchodilator administration was required. Selection was based on screening visits, run‑in assessments, and verification of the inclusion criteria; individuals not meeting these criteria were excluded.

The study is a double‑dummy, double‑blind, randomized, active‑controlled, two‑way crossover trial evaluating QVM149 (indacaterol acetate / glycopyrronium bromide / mometasone furoate) versus salmeterol / fluticasone in adolescents aged 12 to < 18 years with asthma. After an initial screening visit, eligible participants enter a run‑in period during which inhaler technique, compliance, and baseline spirometry are confirmed. At the end of run‑in, participants are randomized 1:1 to receive either QVM149 with placebo comparator or the comparator inhaler with placebo QVM149 for a 12‑week treatment period; the double‑dummy design maintains blinding. Study visits are scheduled at baseline (randomization), weeks 4, 8, and 12 for efficacy (trough FEV₁) and safety assessments, followed by a wash‑out phase before crossing over to the alternate treatment for another 12‑week period with identical visit timing. The end‑of‑study visit occurs after the second treatment period and includes final pulmonary function tests, questionnaire assessments, and safety evaluations. Participant involvement therefore spans approximately 24 weeks of active treatment plus the run‑in and wash‑out intervals. Early termination may occur due to non‑compliance (< 70 % medication or eDiary use), serious adverse events, protocol violations, or withdrawal of consent, and participants discontinuing for any of these reasons will complete an early‑termination visit to collect remaining safety data.

QVM149 is an investigational fixed‑dose combination inhalation powder containing mometasone furoate, glycopyrronium bromide, and indacaterol acetate. The product is supplied in hard capsules for use with a Breezhaler® device. The intended dose is 150 µg indacaterol acetate, 50 µg glycopyrronium bromide, and 160 µg mometasone furoate administered once daily by inhalation. Administration is performed by inhaling the capsule contents as a single dose; the dosing schedule is maintained throughout each 12‑week treatment period. Compliance is assessed by capsule count and electronic inhaler monitoring.

Placebo to QVM149 is an inert inhalation powder formulated to match the appearance and handling characteristics of QVM149. It is administered by inhalation using the same Breezhaler® device, once daily, in parallel with the active comparator arm to preserve blinding. Compliance monitoring follows the same procedures as for the active inhalation product.

AirFluSal Forspiro is the active comparator inhalation powder containing fluticasone propionate 50 µg and salmeterol 500 µg per actuation. The product is pre‑dispensed and delivered via a dry‑powder inhaler. The prescribed regimen is 200 µg total (two actuations) administered twice daily (b.i.d.) for the 12‑week period. Dosing is recorded in patient diaries and inhaler dose counters are reviewed at each visit.

Placebo for Salmeterol xinafoate/fluticasone propionate provides a matching inert powder for the comparator inhaler. It is inhaled twice daily using the same device as the active comparator, ensuring double‑blind conditions. Adherence is evaluated by dose‑counter checks and electronic monitoring.

Seretide Accuhaler is provided as background therapy and contains fluticasone propionate 50 µg and salmeterol 250 µg per inhalation. It is a pre‑dispensed dry‑powder inhaler used according to the standard dosing schedule for the study population (typically one inhalation twice daily). Use of this medication is recorded at each study visit.

Ventolin Evohaler supplies salbutamol 100 µg per puff in a pressurised suspension inhaler and is permitted as rescue medication. Participants may use up to the maximum allowed number of puffs per day, with each use documented in a rescue medication diary. Monitoring of rescue medication frequency contributes to safety assessments.

The primary efficacy endpoint is the change from baseline in trough FEV1 measured at Week 12 of each 12‑week treatment period. Spirometric assessments are performed using standardized forced expiratory volume testing, with values recorded at screening, baseline, and at the Week 12 visit for each crossover period.

Key secondary efficacy parameters include the change from baseline in ACQ‑5 score, the change from baseline in PAQLQ total score, the average use of rescue medication (daily, daytime, and night‑time) over the 12‑week treatment, and the number and severity of asthma exacerbations occurring during each period. The ACQ‑5 and PAQLQ are administered as validated patient‑reported outcome instruments at baseline and Week 12. Rescue medication use is captured through patient diaries throughout the treatment interval, and exacerbations are identified based on predefined clinical criteria and recorded continuously. All efficacy data are analyzed as change from baseline for each parameter, with comparisons between QVM149 and the active comparator performed at the end of each treatment period.