Respiratory
Conditions
Interventions
Salmeterol xinafoate or Fluticasone propionate
Placebo to salmeterol xinafoate fluticasone propionate
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 5.1 Inclusion criteria Participants eligible for inclusion in this study must meet all of the following criteria: 1. Male and female adolescent subjects 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 2022) for a period of at least 1 year prior to screening. 4. 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. 5. 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. 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 subject stay or >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). 7. Subjects 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 = 60 % and < 90 % of the predicted normal value for the subject 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 = 48 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) is allowed at run-in as well as before randomization. Repeat of run-in spirometry can be done later on the same day/visit (only to retest FEV1 criteria, not for reversibility, and before any salbutamol/albuterol inhalation) or in an ad-hoc visit to be scheduled on a later date (within 5 days of original run-in) that would provide sufficient time to receive confirmation from the spirometry data central reviewer of the validity of the assessment before randomization. Run-in medication can be dispensed at run-in visit however the dispensed medication should only be started by the patient if reversibility is met as per ATS/ERS criteria and if all other eligibility criteria as per protocol are met. • A one-time re-screen is allowed in case the subjects fail to meet the criteria at the repeat, provided the subjects return to t
Exclusion criteria
Exclusion criteria: 5.2 Exclusion criteria Participants meeting any of the following criteria are not eligible for inclusion in this study. 1. 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. 2. 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 re- screened 6 weeks after recovery from the exacerbation. 3. Subjects who have ever required intubation for a severe asthma attack/exacerbation. 4. 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 with narrow- angle glaucoma, bladder-neck obstruction or severe renal impairment or urinary retention. 5. 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. 6. 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. 7. Subjects with any chronic conditions affecting the upper respiratory tract (eg.7. 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. 8. 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. 9. Subjects with type I diabetes or uncontrolled type II diabetes. 10. Subjects who have a clinically significant laboratory abnormality before the end of run-in. 11. Use of other investigational drugs within 30 days or 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer. 12. Subjects who, either in the judgment of the investigator or the responsible Novartis personnel, have a clinically significant condition such as (but not limited to) unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure arrhythmia, uncontrolled hypertension, cerebrovascular disease, psychiatric disease, neuro-degenerative diseases or other neurological diseases, uncontrolled hypo- and hyper-thyroidism and other autoimmune diseases, hypokalemia, hyperadrenergic state, or ophthalmologic disorder or subjects with a medical condition that might compromise subject safety or compliance, interfere with evaluat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary estimand is described by the following attributes: 1. Population: Male and female adolescents from 12 years to less than 18 years of age with asthma inadequately controlled on medium or high dose ICS and LABA and a history of at least one severe asthma exacerbation in the previous year. 2. Variable: change from baseline in trough FEV1 at Week12 of each treatment period. 3. Summary measure: mean difference between treatment groups (QVM149 150/50/160 µg o.d. compared with salmeterol/fluticasone 50/500 µg b.i.d.). 4. Treatments of interest: randomized treatment (QVM149 150/50/160 µg o.d. and salmeterol/fluticasone 50/500 µg b.i.d.). | — |
Secondary
| Measure | Time frame |
|---|---|
| o 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 ;To evaluate the safety of QVM149 150/50/160 µg o.d. delivered via Breezhaler | — |
Countries
South Africa
Contacts
Public ContactMichelle Botha
Manager Global Site Activation
Outcome results
None listed