A double-dummy, double-blind, randomized, active controlled, two-way cross-over study with 12-week treatment duration per period, 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

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-06-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2022-502365-26-00

WHO UTN

U1111-1330-7400

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

The primary objective of this study is to demonstrate the superiority of QVM149 150/50/160 µg o.d. delivered via Breezhaler® compared to salmeterol/fluticasone 50/500 µg b.i.d. in trough FEV1 at Week 12 of each treatment period.

Secondary objectives 2

1. To evaluate the efficacy of QVM149 150/50/160 µg o.d. delivered via Breezhaler® compared to salmeterol/fluticasone 50/500 µg b.i.d. in terms of: ● Asthma Control Questionnaire (ACQ-5) score at Week 12 of each treatment period ● Pediatric Asthma Quality of Life Questionnaire (PAQLQ) at Week 12 of each treatment period ● Rescue medication use over 12 weeks of each treatment period ● Asthma exacerbations over 12 weeks of each treatment period
2. To evaluate the safety of QVM149 150/50/160 µg o.d. delivered via Breezhaler®

Conditions and MedDRA coding

Asthma

Regulatory references

Scientific advice from competent authorities

European Medicines Registration Consultancy Limited

EMA paediatric investigation plan (PIP)

EMEA-001812-PIP01-15

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male and female adolescent participants aged from ≥ 12 years old to less than 18 years old at screening visit.
2. Signed informed consent must be obtained prior to participation in the study. 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.
3. Patients with a documented diagnosis of persistent asthma (according to GINA 2024) for a period of at least 1 year prior to screening.
4. Participants who have used medium or high dose ICS with LABA in combination (GINA 2024) for asthma for at least 3 months and at stable doses for at least 1 month prior to screening.
5. Participants must be symptomatic / inadequately controlled according to the investigator’s opinion despite treatment with medium or high stable doses of ICS with LABA in combination (GINA 2024) before screening.
6. 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 participant stay or >24-hour stay in an observation area in the emergency room of other equivalent facility). NOTE: Investigators must use appropriate means to ensure the accuracy of the participant’s exacerbation history (participant history at screening documented in source notes, pharmacy records, hospital records, or chart records are acceptable).
7. Participants must have ACQ-5 score ≥ 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.
8. Pre-bronchodilator FEV1 ≥ 50% of the predicted normal value for the participant according to ATS/ERS 2019 criteria after withholding bronchodilators (see Table 6-7) at both run-in and before randomization. Withholding/washout period of bronchodilators prior to spirometry: • SABA for ≥ 6 hours • FDC or free combinations of ICS/LABA for ≥ 24 hours • Short acting anticholinergics (SAMA) for ≥ 8 hours • Xanthines ≥ 7 days NOTES: • In case of combination ICS/LABA at screening, ICS alone should be continued until run-in visit. • Wash-out period of each drug should be adhered to as above and should not be longer. If wash-out period is considered to be longer please contact the Novartis Medical Monitor. • A one-time repeat of percent predicted FEV1 (pre-bronchodilator FEV1) within 5 days of the initial visit is allowed at run-in as well as before randomization. That would provide sufficient time to receive confirmation from the spirometry data central reviewer of the validity of the assessment. At Run-in visit, the run-in medication should be dispensed only once the repeat spirometry was qualified, and if all inclusion criteria at Run-in visit are successfully met. • A one-time re-screen is allowed in case the participants fail to meet the criteria at the repeat, provided the participants return to their previous treatment until re-screening. In this circumstance, participants are not required to go back on prior medication for 1 full month duration as outlined in inclusion criterion 4.
9. Participants who demonstrate an increase in FEV1 of ≥ 12% within 15 to 30 minutes after administration of 200-400 μg salbutamol/180-360 μg albuterol (or equivalent dose) at runin visit. All participants must perform a reversibility test at run-in visit that will be evaluated by central overread. If reversibility is not demonstrated at run-in visit, or the assessment was evaluated as unacceptable by the central overread then: • Spirometry assessment to demonstrate reversibility should be repeated once in an adhoc visit to be scheduled preferably within 5 days. The reversibility test cannot be repeated on the same day because of the wash-out period of salbutamol/albuterol. • 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 screening. • Alternatively, participants may be permitted to enter the study with a historical positive broncho-provocation test that was performed within 2 years prior to screening. If reversibility is not demonstrated at run-in visit (or after repeated assessment at ad-hoc visit within 5 days) with acceptable spirometry quality as per overread and historical evidence of reversibility/broncho-provocation is not available (or was not performed according to ATS/ERS guidelines) participants must be screen failed. Spacer devices are permitted during reversibility testing only. The Investigator or delegate may decide whether to use spacer or not for the reversibility testing.
10. Participants must meet all the following criteria at end of run-in visit prior to randomization: • Participants must demonstrate acceptable inhaler devices (as per investigator judgement), peak flow meter, and spirometry techniques during the run-in period (from beginning to end of run-in). • Participants must demonstrate ≥ 70% compliance with the asthma controller ICS/LABA during the run-in period based on their inhaler use count. 70% compliance is defined as medication taken in 70% of the days in that period. • Participants must demonstrate ≥ 70% compliance with required use of the eDiary during the run-in period. 70% compliance is defined as completing the daily eDiary for 70% of the days (either morning or evening, including at least 7 morning and 7 evening eDiaries) during the run-in period.

Exclusion criteria 10

1. Participants 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
2. Participants who have had a severe asthma attack/exacerbation requiring systemic steroids OR hospitalization (> 24 hours) OR emergency room visit (≤ 24 hours) within 6 weeks of screening. If participants 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.
3. Participants who have ever required intubation for a severe asthma attack/exacerbation.
4. 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.
5. Participants 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. Participants may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
6. Participants 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. Participants may be re-screened once their candidiasis has been treated and has resolved.
7. Participants 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.
8. Participants 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.
9. Participants with type I diabetes or uncontrolled type II diabetes.
10. Participants who have a clinically significant laboratory abnormality as per investigator judgement before the end of run-in.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ● Change from baseline in trough FEV1 at Week 12 of each treatment period.

Secondary endpoints 2

1. ● Change from baseline in (ACQ-5) score at Week 12 of each treatment period ● Change from baseline in (PAQLQ) total score at Week 12 of each treatment period ● Change from baseline in average rescue medication use (daily, daytime, and night-time) over 12 weeks of each treatment period ● Number and severity of reported asthma exacerbations over 12 weeks of each treatment period
2. Safety assessments including incidence of adverse events, serum cortisol, blood glucose, serum potassium, electrocardiography, local side effects of ICS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 5

Locations

4 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 56 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications