E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of once daily fluticasone FF/VI with once daily FF in participants with asthma. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of FF/VI in participants with asthma. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants must be between 5 and 17 years of age inclusive, at the time of signing the informed consent.
2. A history of symptoms consistent with a diagnosis of asthma for at least 6 months.
3. Pre-bronchodilator FEV1 >50% to ≤90% predicted normal. A minimum of 2 efforts that are considered acceptable (not necessarily repeatable) are required to be eligible (see Section 9.1.1).
NOTE: Participants who are unable to perform the pre-bronchodilator FEV1 manoeuvre at Visit 1 can, at the discretion of the investigator, attend the clinic once more on the day after Visit 1 to attempt to perform the pre-bronchodilator and post-bronchodilator FEV1 manoeuvres. These FEV1 measurements must be acceptable and must meet the FEV1 inclusion limits and the reversibility requirements (below) to be eligible for the study. Participants who do provide a pre-bronchodilator FEV1 on Visit 1 cannot make another attempt on the day after.
4. Lung function reversibility defined as an increase of ≥12% in FEV1 within 10 to 40 minutes following 2 to 4 inhalations of salbutamol inhalation aerosol (or 1 nebulised treatment with albuterol/salbutamol solution). Use of a spacer is permitted.
5. Uncontrolled asthma, with a cACT/ACT score ≤19.
6. Receiving stable asthma therapy (SABA inhaler plus ICS [total daily dose ≤FP 250 mcg or equivalent]) for at least 4 weeks prior to Visit 1 (ie, screening).
7. Able to replace their current SABA treatment with salbutamol aerosol inhaler at Visit 1 for use as needed for the duration of the study. Salbutamol metered dose inhaler (MDI) will be administered with or without a spacer, to be used as determined by the investigator. The use or non-use of the spacer should be consistent for an individual participant throughout the study.
8. Male or female participants. Females of reproductive potential must agree to follow 1 of the options listed (which include abstinence) in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (see Section 12.4) from 30 days prior to the first dose of study medication and until at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer after the last dose of study medication and completion of the follow-up call. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.
9. Written informed consent from at least 1 parent/care giver (legal guardian) and accompanying informed assent from the participant (where the participant is able to provide assent) prior to admission to the study.
• If applicable, participant must be able and willing to give assent to take part in the study according to the local requirement. The study investigator is accountable for determining a child's capacity to assent to participation in a research study, taking into consideration any standards set by the responsible IEC.
• Participant and their legal guardian(s) understand that the study requires them to be treated on an outpatient basis.
• Participant and their legal guardian(s) understand that they must comply with study medication and study assessments including recording of PEF and rescue SABA use, attending scheduled study visits, and being accessible by a telephone call. |
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E.4 | Principal exclusion criteria |
1. A history of life threatening asthma defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
2. Any asthma exacerbation requiring the use of oral steroids within 6 weeks of Visit 1, systemic or depot corticosteroids within 12 weeks of Visit 1, OR ER attendance within 3 months of Visit 1 OR hospitalisation within 6 months of Visit 1.
3. A culture documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that has not resolved within 4 weeks of Visit 1 and which led to a change in asthma management or, in the opinion of the investigator, is expected to affect the participant’s asthma status or the participant’s ability to participate in the study.
4. Clinical visual evidence of oropharyngeal candidiasis.
5. Fasting blood glucose at screening >100 mg/dl (5.6mol/L). NOTE: Participants who have a value that is above >100 mg/dl can have a repeat test before Visit 2.
6. Obesity (BMI above the 97th centile based on the CDC charts).
7. Any significant abnormality or medical condition identified at the screening medical assessment (including serious psychological disorder) that in the investigator’s opinion, preclude entry into the study due to risk to the participant or that may interfere with the conduct and/or outcome of the study.
8. QTc >450 msec or QTc >480 msec in participants with bundle branch block or any other clinically significant abnormality in the Screening 12-lead ECG.
Notes:
• The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or manually over-read.
• The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial.
• For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
Prior/Concomitant Therapy
9. Use of any prohibited medications listed in Section 7.7.1. of Protocol.
10. Present use of any tobacco products.
11. Drug allergies: any adverse reaction including immediate or delayed hypersensitivity to any beta 2-agonists, sympathomimetic drug or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the ELLIPTA Inhaler (i.e. lactose or magnesium stearate).
12. Milk Protein Allergy: history of severe milk protein allergy.
13. Participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, five half-lives or twice the duration of the biological effect of the study treatment (whichever is longer).
14. Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
15. An affiliation with the investigator site: the parents/guardians or child is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
16. The parent or guardian has a history of psychiatric disease, intellectual deficiency, substance abuse or other condition (e.g. inability to read, comprehend or write) which may affect:
• validity of consent to participate in the study
• adequate supervision of the participant during the study
• compliance of participant with study medication and study procedures (e.g. completion of daily diary, attending scheduled clinic visits)
• participant safety and well-being
17. Children in care: children who are wards of the government or state are not eligible for participation in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
For 5-11 years population:
• Change from baseline, averaged over weeks 1-12 of the treatment period, in pre-dose (i.e. trough) morning peak expiratory flow (PEF), captured daily via electronic patient diary.
For 5-17 years population:
• Weighted mean FEV1 (0-4 hours) at week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
For 5-11 years population:
• Weighted mean FEV1 (0-4 hours) at week 12.
For 5-17 years population:
• Change from baseline, averaged over weeks 1-12 of the treatment period, in pre-dose (i.e. trough) morning peak expiratory flow (PEF), captured daily via electronic patient diary.
Common for 5-11 and 5-17 years population:
• Change from baseline in the percentage of rescue-free 24-hour periods over weeks 1-12 of the treatment period (powered secondary endpoint for 5-11 years population) captured daily via electronic patient diary.
• Change from baseline in the percentage of symptom-free 24-hour periods over weeks 1-12 of the treatment period, captured daily via electronic patient diary.
• Change from baseline in morning (AM) forced expiratory flow in 1 second (FEV1) in participants who can perform the manoeuvre at week 12.
• Change from baseline in ACQ-5 at week 24.
• Incidence of exacerbations over the 24 week treatment period.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Canada |
China |
Japan |
Mexico |
South Africa |
United States |
Poland |
Romania |
Spain |
Germany |
Italy |
Russian Federation |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the last visit of the last participant in the study or last scheduled procedure shown in the SOA. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |