Double-blind, randomized, active-controlled, two-way cross-over study, with 12-week treatment duration per period, to evaluate the efficacy and safety of QMF149 (indacaterol acetate / mometasone furoate) compared to budesonide in children from 6 to less than 12 years of age with asthma

The primary objective of this study is to demonstrate that **indacaterol acetate/mometasone furoate** (QMF149) is superior to budesonide in enhancing lung function, specifically measured by forced expiratory volume in one second (FEV1), at Week 12 of each treatment period in children aged 6 to less than 12 years with **asthma**. This is clinically relevant as improved lung function is a critical indicator of effective asthma management, potentially leading to better overall respiratory health and quality of life in pediatric patients.

Secondary objectives include:

• Assessing pediatric asthma symptoms using the Asthma Control Questionnaire for Infants and Young Children (ACQ-IA), measuring peak expiratory flow rate (PEFR), and recording the number of asthma exacerbations over 12 weeks of each treatment period to evaluate if QMF149 is more effective than budesonide.
• Measuring and comparing the use of rescue medication (salbutamol/albuterol) over 12 weeks with each treatment through e-diary recordings of rescue usage, including daily, night-time, and daytime use.
• Documenting any medical problems, termed "adverse events," that occur during the trial, which may or may not be attributed to the trial drug.

The clinical trial involves a total of **100 participants** diagnosed with **asthma**. The study population consists of both male and female children aged between 6 to less than 12 years. Participants have had asthma for at least one year prior to enrollment and were inadequately controlled on low-dose inhaled steroids or previously controlled on a combination therapy but showed inadequate control during the trial's run-in period. The trial population was selected based on these criteria to ensure the inclusion of children who qualify for treatment with low-dose inhaled corticosteroids plus a long-acting beta agonist. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, as it involves children, but no additional details on health status or habits are provided.

The clinical trial is designed as a **randomized**, **double-blind**, active-controlled, two-way cross-over study to evaluate the efficacy and safety of QMF149, which contains **indacaterol acetate** and **mometasone furoate**, compared to **budesonide** in children aged 6 to less than 12 years with **asthma**. The trial consists of two treatment periods, each lasting 12 weeks, with a total estimated trial duration extending until August 31, 2026. Participants will be involved in the study for a maximum of 24 weeks, including the treatment periods and any necessary follow-up visits.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is assessed based on criteria such as age, asthma diagnosis, and current treatment regimen. Following successful screening, participants enter a run-in period where they receive a low-dose inhaled steroid, **fluticasone propionate**, to establish baseline asthma control. The primary endpoint is the change from baseline in lung function, specifically **FEV1**, at Week 12 of each treatment period. Secondary endpoints include changes in pediatric asthma symptoms, peak expiratory flow rate, and the frequency of asthma exacerbations, as well as the use of rescue medication.

Participants will attend regular follow-up visits throughout the trial to monitor safety and efficacy outcomes. These visits will include clinical assessments, laboratory tests, and electrocardiograms (ECGs) to evaluate any untoward effects. The end-of-study visit will occur after the completion of the second treatment period, where final assessments will be conducted. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant or their guardian.

The clinical trial involves several treatments, including both experimental and non-experimental medications. The **experimental medication** is QMF149, which is an **inhalation powder** in a hard capsule form. It contains the active substances **mometasone furoate** and **indacaterol acetate**. This medication is administered via inhalation using a unit-dose dry powder inhalation device known as the Breezhaler. The device is designed to ensure proper aerosolization of the medication and prevent capsule ingestion. The maximum daily dose is one dosage form, with a total treatment period of up to 12 weeks.

The **comparator treatment** in the study is Miflonide Breezhaler, which is also an **inhalation powder** in a hard capsule form containing the active substance **budesonide**. This medication is administered using a similar Breezhaler device, ensuring consistency in the method of administration. The maximum daily dose for Miflonide Breezhaler is 200 micrograms, with a total treatment period of up to 12 weeks.

The study also includes a **placebo** treatment, which is a generic placebo hard non-gelatin capsule for inhalation. The placebo is designed to match the active dosage form used in the trial and contains inactive excipients such as magnesium stearate and lactose monohydrate. This ensures blinding in the study, as the placebo capsules are visually identical to those used for the active drug product.

Additional non-experimental treatments include **fluticasone propionate** and **salbutamol**, both administered as **inhalation powders**. Fluticasone propionate has a maximum daily dose of 125 micrograms and a treatment period of up to 6 weeks. Salbutamol, on the other hand, has a maximum daily dose of 800 micrograms and a treatment period of up to 190 days. These medications are used as auxiliary treatments to manage asthma symptoms in the study participants.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the treatment protocols. The study is designed to evaluate the efficacy and safety of QMF149 compared to budesonide in improving lung function in children with asthma over a 12-week treatment period.

Efficacy in this clinical trial will be assessed primarily through the change from baseline in lung function, specifically the forced expiratory volume in one second (**FEV1**), at Week 12 of each treatment period. This primary endpoint aims to demonstrate the superiority of the combination of indacaterol acetate and mometasone furoate (QMF149) over budesonide in improving lung function in children aged 6 to less than 12 years with asthma.

Secondary endpoints include the change from baseline in pediatric asthma symptoms as measured by the Asthma Control Questionnaire for Infants and Young Children (ACQ-IA), peak expiratory flow rate (PEFR) scores, and the frequency of asthma flare-ups at Week 12. Additionally, the use of rescue medication will be monitored, with changes in daytime, nighttime, and daily usage recorded over the 12-week treatment period. Safety assessments will also be conducted, evaluating all adverse effects through clinical assessments, laboratory tests, electrocardiograms (ECGs), and patient history.