Last updated: 06/04/2025 19:40:07
Safety and efficacy study of fluticasone furoate/vilanterol (FF/VI) fixed dose combination (FDC) compared to FF alone in subjects with asthma
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A randomised, double-blind, parallel group, multicentre, stratified, study evaluating the efficacy and safety of once daily fluticasone furoate/vilanterol inhalation powder compared to once daily fluticasone furoate inhalation powder in the treatment of asthma in participants aged 5 to 17 years old (inclusive) currently uncontrolled on inhaled corticosteroids
Trial description: The goal of asthma treatment is to achieve and maintain asthma control and to reduce the future risk of exacerbations. Inhaled corticosteroids (ICS) are considered as the most effective anti- inflammatory treatment for all severities of persistent asthma. For children >=5 years of age and adolescents whose asthma is uncontrolled, low-dose ICS plus adjunctive therapy with long-acting beta agonist (LABA) is considered as effective. Thus, this study is designed to evaluate the efficacy and safety of FF (ICS component)/VI (LABA component) compared to FF alone for the treatment of asthma, in subjects aged 5 to 17 years old currently uncontrolled on ICS. The study will be conducted over a total duration of approximately 29 weeks: 4 week run-in period, 24-week double-blind treatment period and 1-week follow-up period. Subjects will be randomized to receive FDC of FF/VI or FF administered via ELLIPTA® dry powder inhaler (DPI). The dose of both FF/VI and FF alone will be selected based on the age of subjects. Subjects will receive a short acting beta 2 agonist (SABA) (albuterol /salbutamol) as a rescue medication throughout the study. A total of 870 subjects will be randomized in the study. Of this, 652 subjects will be aged 5 to 11 years (cohort A), and 218 will be aged 12 to 17 years inclusive (cohort B). ELLIPTA is a registered trademark of GlaxoSmithKline (GSK) group of companies.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Absolute weighted mean of forced expiratory volume in 1 second (FEV1) (0-4 hours) at week 12 in 5-17 year old population
Timeframe: Week 12
Change from baseline in mean pre-dose morning peak expiratory flow (AM PEF) in 5-11 year old population
Timeframe: Baseline and Week 1-12
Secondary outcomes:
Change from baseline in mean pre-dose AM PEF period in 5-17 year old population
Timeframe: Baseline and Week 1-12
Absolute weighted mean of FEV1 (0-4 hours) at week 12 in 5-11 year old population
Timeframe: Week 12
Change from baseline in the percentage of rescue-free 24-hour periods over weeks 1-12 of the treatment period in 5-17 year old population
Timeframe: Baseline and Week 1-12
Change from baseline in the percentage of symptom-free 24-hour periods over weeks 1-12 of the treatment period in 5-17 year old population
Timeframe: Baseline and Week 1-12
Change from baseline in morning (AM) FEV1 at week 12 in 5-17 year old population
Timeframe: Baseline and Week 12
Change from Baseline in asthma control questionnaire (ACQ-5) Score at week 24 in 5-17 year old population
Timeframe: Baseline and Week 24
Change from baseline in the percentage of rescue-free 24-hour periods over weeks 1-12 of the treatment period in 5-11 year old population
Timeframe: Baseline and Week 1-12
Change from baseline in the percentage of symptom-free 24-hour periods over weeks 1-12 of the treatment period in 5-11 year old population
Timeframe: Baseline and Week 1-12
Change from baseline in morning (AM) FEV1 at week 12 in 5-11 year old population
Timeframe: Baseline and Week 12
Change from baseline ACQ-5 Score at week 24 in 5-11 year old population
Timeframe: Baseline and Week 24
Number of participants with adverse events (AEs) and serious adverse events (SAEs) in 5-17 year old population
Timeframe: Up to week 25
Number of participants with abnormal electrocardiogram (ECG) findings in 5-17 year old population
Timeframe: Week 24
Change from baseline in fasting glucose in 5-17 year old population
Timeframe: Baseline and Week 24
Number of participants with any incidence of asthma exacerbation over the 24-week treatment period in 5-17 year old population
Timeframe: Up to week 24
Number of participants with AEs and SAEs in 5-11 year old population
Timeframe: Up to week 25
Number of participants with abnormal ECG findings in 5-11 year old population
Timeframe: Week 24
Change from baseline in fasting glucose in 5-11 year old population
Timeframe: Baseline and Week 24
Number of participants with any incidence of asthma exacerbation over the 24-week treatment period in 5-11 year old population
Timeframe: Up to week 24
Interventions:
Drug: FF/VI via ELLIPTA DPI
Drug: FF via ELLIPTA DPI
Enrollment:
906
Observational study model:
Not applicable
Primary completion date:
2022-21-03
Time perspective:
Not applicable
Clinical publications:
Philippe Bareille, Richard Forth, Varsha Imber, Irina Bondarenko, Arthur Michaud, Bernadetta Majorek-Olechowska. Once-daily fluticasone furoate/vilanterol vs once-daily fluticasone furoate in patients with asthma aged 5 to 17 years. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2024-Jun-25; doi:10.1016/j.anai.2024.06.024 http://dx.doi.org/S1081-1206(24)00376-410.1016/j.anai.2024.06.024
PMID: 38936466
DOI: 10.1016/j.anai.2024.06.024
Medical condition
Asthma
Product
fluticasone furoate, fluticasone furoate/vilanterol, vilanterol
Collaborators
Not applicable
Study date(s)
October 2017 to March 2022
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
5 - 17 years
Accepts healthy volunteers
No
- For all subjects: Between 5 and 17 years of age inclusive, at the time of signing the informed consent.
- A history of symptoms consistent with a diagnosis of asthma for at least 6 months.
- For all subjects: History of life threatening asthma defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
- 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 hospitalization within 6 months of Visit 1.
Inclusion and exclusion criteria
Inclusion criteria:
- For all subjects: Between 5 and 17 years of age inclusive, at the time of signing the informed consent.
- A history of symptoms consistent with a diagnosis of asthma for at least 6 months.
- Pre-bronchodilator FEV1 >50 percent to <=90 percent predicted normal. A minimum of 2 efforts that are considered acceptable (not necessarily repeatable) are required to be eligible.
- Lung function reversibility defined as an increase of >=12 percent in FEV1 within 10 to 40 minutes following 2 to 4 inhalations of salbutamol inhalation aerosol (or 1 nebulized treatment with albuterol/salbutamol solution). Use of a spacer is permitted.
- Uncontrolled asthma, with a childhood asthma control test (cACT)/ACT score <=19.
- Receiving stable asthma therapy (SABA inhaler plus ICS [total daily dose <=FP 250 micrograms (mcg) or equivalent]) for at least 4 weeks prior to Visit 1 (i.e. screening).
- 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 subject throughout the study.
- Male or female subjects will be included. 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) 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 subjects understand how to properly use these methods of contraception.
- Written informed consent from at least 1 parent/care giver (legal guardian) and accompanying informed assent from the subject (where the subject is able to provide assent) prior to admission to the study. If applicable, subject 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 independent ethics committee (IEC); subject and their legal guardian(s) understand that the study requires them to be treated on an outpatient basis; subject 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.
- For subjects eligible for randomization; asthma control: uncontrolled asthma, with a cACT/ACT score <=19.
- A technically acceptable pre-bronchodilator FEV1 >50 percent to <=90 percent predicted normal at Visit 2. A minimum of 2 efforts that are considered acceptable and repeatable following the over read are required to be eligible.
- Symptoms and rescue use: demonstrated and reported in a daily diary symptoms of asthma (a score of >=1 on the day-time or night-time asthma symptom scores) and/or daily albuterol/salbutamol on at least 3 of the last 7 consecutive days of the run-in period (not including the date of randomization).
- Compliance with run-in medication: compliance is defined as use of run-in medication on at least 4 of the last 7 consecutive days of the run-in period (not including the date of randomization) recorded in the electronic subject diary.
- Compliance with completion of the daily diary reporting: defined as completion of all questions on 4 out of the last 7 days during the run-in period (not including the date of randomization).
Exclusion criteria:
- For all subjects: History of life threatening asthma defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
- 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 hospitalization within 6 months of Visit 1.
- 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 subject’s asthma status or the subject’s ability to participate in the study.
- Clinical visual evidence of oropharyngeal candidiasis.
- Fasting blood glucose at screening >100 milligrams/deciliter (mg/dL) (5.6 moles per liter [mol/L]).
- Obesity (Body Mass Index [BMI] above the 97th centile based on the centers for disease control and prevention [CDC] charts).
- 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 subject or that may interfere with the conduct and/or outcome of the study.
- QTc >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block or any other clinically significant abnormality in the screening 12-lead ECG.
- Use of any prohibited medications.
- Present use of any tobacco products.
- 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).
- Milk Protein Allergy: history of severe milk protein allergy.
- 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).
- Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
- 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.
- The parent or guardian has a history of psychiatric disease, intellectual deficiency, substance abuse or other condition (example, inability to read, comprehend or write) which may affect: validity of consent to participate in the study; adequate supervision of the subject during the study; compliance of subject with study medication and study procedures (example, completion of daily diary, attending scheduled clinic visits); subject safety and well-being.
- Children in care: children who are wards of the government or state are not eligible for participation in this study.
- For subjects eligible for randomization; Changes in asthma medication that occur after screening.
- Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that led to a change in asthma management or, in the opinion of the investigator, is expected to affect the subject’s asthma status or the subject’s ability to participate in the study.
- Evidence of an exacerbation, defined as a: deterioration of asthma requiring the use of oral corticosteroids for at least 3 days, or a depot corticosteroid injection, or an in-patient hospitalization due to asthma that required systemic corticosteroids between screening and randomization.
- Clinical visual evidence of oropharyngeal candidiasis at the randomization Visit.
- Unable to use the ELLIPTA inhaler correctly.
Trial location(s)
Location
GSK Investigational Site
Asheville, North Carolina, United States, 28801
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21236
Status
Study Complete
Location
GSK Investigational Site
Berazategui, Buenos Aires, Argentina, 1837
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, C1121ABE
Status
Study Complete
Location
GSK Investigational Site
CABA, Buenos Aires, Argentina, C1028AAP
Status
Study Complete
Location
GSK Investigational Site
Charlotte, North Carolina, United States, 28277
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1122AAK
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1121ABE
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80206
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32827
Status
Study Complete
Location
GSK Investigational Site
Evanston, Illinois, United States, 60201
Status
Study Complete
Location
GSK Investigational Site
Evansville, Indiana, United States, 47715
Status
Study Complete
Location
GSK Investigational Site
Florida, Buenos Aires, Argentina, 1602
Status
Study Complete
Location
GSK Investigational Site
Gainesville, Georgia, United States, 30501
Status
Study Complete
Location
GSK Investigational Site
Geesthacht, Schleswig-Holstein, Germany, 21502
Status
Study Complete
Location
GSK Investigational Site
Great Neck, New York, United States, 11021
Status
Study Complete
Location
GSK Investigational Site
Grove City, Ohio, United States, 43123
Status
Study Complete
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69126
Status
Study Complete
Location
GSK Investigational Site
Huntington Beach, California, United States, 92648
Status
Study Complete
Location
GSK Investigational Site
Johannesburg, Gauteng, South Africa, 1818
Status
Study Complete
Location
GSK Investigational Site
La Plata, Buenos Aires, Argentina, 1900
Status
Study Complete
Location
GSK Investigational Site
Lanús, Buenos Aires, Argentina, B1824KAJ
Status
Study Complete
Location
GSK Investigational Site
Lewisville, Texas, United States, 75067
Status
Study Complete
Location
GSK Investigational Site
Little Rock, Arkansas, United States, 72205
Status
Study Complete
Location
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68161
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, 7600
Status
Study Complete
Location
GSK Investigational Site
Miami Lakes, Florida, United States, 33014
Status
Study Complete
Location
GSK Investigational Site
Middelburg, Mpumalanga, South Africa, 1055
Status
Study Complete
Location
GSK Investigational Site
Nueve de Julio, Buenos Aires, Argentina, B6500BWQ
Status
Study Complete
Location
GSK Investigational Site
Orangeburg, South Carolina, United States, 29118-2040
Status
Study Complete
Location
GSK Investigational Site
Ostrowiec Swietokrzyski, Poland, 27-400
Status
Study Complete
Location
GSK Investigational Site
Owensboro, Kentucky, United States, 42301
Status
Study Complete
Location
GSK Investigational Site
Panorama, Western Province, South Africa, 7500
Status
Study Complete
Location
GSK Investigational Site
Piscataway, New Jersey, United States, 08854
Status
Study Complete
Location
GSK Investigational Site
Raleigh, North Carolina, United States, 27607
Status
Study Complete
Location
GSK Investigational Site
Riverside, California, United States, 92506
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78207
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78215
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78249
Status
Study Complete
Location
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Status
Study Complete
Location
GSK Investigational Site
Summerville, South Carolina, United States, 29485
Status
Study Complete
Location
GSK Investigational Site
Verona, New Jersey, United States, 07044
Status
Study Complete
Location
GSK Investigational Site
Wexford, Pennsylvania, United States, 15090
Status
Study Complete
Location
GSK Investigational Site
White Marsh, Maryland, United States, 21162
Status
Study Complete
Location
GSK Investigational Site
Ypsilanti, Michigan, United States, 48197
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80230
Status
Study Complete
Location
GSK Investigational Site
Oak Park, Illinois, United States, 60301
Status
Study Complete
Location
GSK Investigational Site
OKLAHOMA CITY, Oklahoma, United States, 73120
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32806
Status
Study Complete
Location
GSK Investigational Site
Savannah, Georgia, United States, 31406
Status
Study Complete
Location
GSK Investigational Site
Dallas, Texas, United States, 75231-4307
Status
Study Complete
Location
GSK Investigational Site
Greenville, South Carolina, United States, 29607
Status
Study Complete
Location
GSK Investigational Site
Colorado Springs, Colorado, United States, 80907
Status
Study Complete
Location
GSK Investigational Site
NEW HARTFORD, New York, United States, 13413
Status
Study Complete
Location
GSK Investigational Site
Aventura, Florida, United States, 33180
Status
Study Complete
Location
GSK Investigational Site
Belleville, New Jersey, United States, 07109
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bologna, Emilia-Romagna, Italy, 40138
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Brick, New Jersey, United States, 08724
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ciudad de México, Ciudad de Mexico, Mexico, 06100
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Corunna, Ontario, Canada, N0N 1G0
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Edison, New Jersey, United States, 08820
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Guadalajara, Jalisco, Mexico, 44130
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30173
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hialeah, Florida, United States, 33016
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Homestead, Florida, United States, 33030
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Krugersdorp, Gauteng, South Africa, 1752
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Madison, Wisconsin, United States, 53792
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Majadahonda (Madrid), Spain, 28222
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55402
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Diego, California, United States, 92123
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Miguel de Tucumán, Tucumán, Argentina, T4000IHE
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Santiago de Compostela, Spain, 15706
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Warrensburg, Missouri, United States, 64093
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Winter Park, Florida, United States, 32789
Status
Terminated/Withdrawn
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2022-21-03
Actual study completion date
2022-21-03
Plain language summaries
Summary of results in plain language
Available language(s): English, Afrikaans, Bulgarian, French (Canadian), German, Hungarian, Italian, Lithuanian, Polish, Romanian, Russian, Spanish (Argentina), Spanish (Mexico), Spanish, Spanish (United States), Japanese
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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