Safety and Efficacy Study of Fluticasone Furoate/Vilanterol (FF/VI) Fixed Dose Combination (FDC) Compared to FF Alone in Subjects With Asthma

NCT ID: NCT03248128

Last Updated: 2025-06-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

906 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-20

Study Completion Date

2022-03-21

Brief Summary

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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.

Detailed Description

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Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects will be randomized to receive FDC of FF/VI inhalation powder compared to FF inhalation powder, once daily in cohort A and cohort B.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
This will be a double blind study. Subjects and investigator will be masked.

Study Groups

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Subjects receiving FF/VI in cohort A

Subjects will be randomized in 1:1 ratio to receive a FDC of FF/VI with a dose of 50/25 mcg administered once daily in the morning via ELLIPTA DPI.

Group Type EXPERIMENTAL

FF/VI via ELLIPTA DPI

Intervention Type DRUG

ELLIPTA DPI inhaler will contain two individual blister strips; the first strip will contain FF(50 or 100 mcg) and second strip will contain VI (25 mcg).

Subjects receiving FF in cohort A

Subjects will be randomized in 1:1 ratio to receive FF with a dose of 50 mcg administered once daily in the morning via ELLIPTA DPI.

Group Type ACTIVE_COMPARATOR

FF via ELLIPTA DPI

Intervention Type DRUG

ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).

Subjects receiving FF/VI in cohort B

Subjects will be randomized in 1:1 ratio to receive a FDC of FF/VI with a dose of 100/25 mcg administered once daily in the morning via ELLIPTA DPI.

Group Type EXPERIMENTAL

FF/VI via ELLIPTA DPI

Intervention Type DRUG

ELLIPTA DPI inhaler will contain two individual blister strips; the first strip will contain FF(50 or 100 mcg) and second strip will contain VI (25 mcg).

Subjects receiving FF in cohort B

Subjects will be randomized in 1:1 ratio to receive FF with a dose of 100 mcg administered once daily in the morning via ELLIPTA DPI.

Group Type ACTIVE_COMPARATOR

FF via ELLIPTA DPI

Intervention Type DRUG

ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).

Interventions

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FF/VI via ELLIPTA DPI

ELLIPTA DPI inhaler will contain two individual blister strips; the first strip will contain FF(50 or 100 mcg) and second strip will contain VI (25 mcg).

Intervention Type DRUG

FF via ELLIPTA DPI

ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

5 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Hoover, Alabama, United States

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Little Rock, Arkansas, United States

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Huntington Beach, California, United States

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Riverside, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Denver, Colorado, United States

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Aventura, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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Ocala, Florida, United States

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Orlando, Florida, United States

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Orlando, Florida, United States

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Gainesville, Georgia, United States

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Savannah, Georgia, United States

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Evanston, Illinois, United States

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Oak Park, Illinois, United States

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Evansville, Indiana, United States

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Owensboro, Kentucky, United States

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Baltimore, Maryland, United States

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White Marsh, Maryland, United States

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Ypsilanti, Michigan, United States

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Piscataway, New Jersey, United States

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Verona, New Jersey, United States

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Great Neck, New York, United States

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New Hartford, New York, United States

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Asheville, North Carolina, United States

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Charlotte, North Carolina, United States

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Raleigh, North Carolina, United States

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Grove City, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Medford, Oregon, United States

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Wexford, Pennsylvania, United States

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Greenville, South Carolina, United States

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Orangeburg, South Carolina, United States

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Spartanburg, South Carolina, United States

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Summerville, South Carolina, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Lewisville, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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Waco, Texas, United States

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Murray, Utah, United States

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Berazategui, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Florida, Buenos Aires, Argentina

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La Plata, Buenos Aires, Argentina

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Lanús, Buenos Aires, Argentina

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Lobos, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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Nueve de Julio, Buenos Aires, Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Mendoza, , Argentina

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Rosario, , Argentina

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Santa Fe, , Argentina

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Stara Zagora, , Bulgaria

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Brampton, Ontario, Canada

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Windsor, Ontario, Canada

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Québec, , Canada

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Panzhihua, Sichuan, China

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Taiyuan, , China

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Heidelberg, Baden-Wurttemberg, Germany

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Mannheim, Baden-Wurttemberg, Germany

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Rosenheim, Bavaria, Germany

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Geesthacht, Schleswig-Holstein, Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Szeged, , Hungary

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Parma, Emilia-Romagna, Italy

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Rome, Lazio, Italy

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Bergamo, Lombardy, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Palermo, Sicily, Italy

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Ancona, The Marches, Italy

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Perugia, Umbria, Italy

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Chiba, , Japan

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Fukui, , Japan

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Fukuoka, , Japan

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Fukuoka, , Japan

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Hiroshima, , Japan

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Hokkaido, , Japan

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Hokkaido, , Japan

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Hyōgo, , Japan

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Kanagawa, , Japan

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Osaka, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Vilnius, , Lithuania

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Guadalajara, Jalisco, Mexico

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Guadalajara, Jalisco, Mexico

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Zapopan, Jalisco, Mexico

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Monterrey, Nuevo León, Mexico

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Monterrey, Nuevo León, Mexico

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Villahermosa, Tabasco, Mexico

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Bialystok, , Poland

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Częstochowa, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Ostrowiec Świętokrzyski, , Poland

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Ostrów Wielkopolski, , Poland

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Poznan, , Poland

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Skierniewice, , Poland

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Strzelce Opolskie, , Poland

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Tarnów, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Zawadzkie, , Poland

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Brasov, , Romania

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Brasov, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Târgu Mureş, , Romania

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Krasnodar, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Omsk, , Russia

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Penza, , Russia

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Perm, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Saransk, , Russia

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Saratov, , Russia

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St'Petersburg, , Russia

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Tomsk, , Russia

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Ufa, , Russia

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Volgograd, , Russia

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Voronezh, , Russia

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Yaroslavl, , Russia

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Boksburg, Gauteng, South Africa

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Johannesburg, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Middelburg, Mpumalanga, South Africa

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Panorama, Western Province, South Africa

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Bellville, , South Africa

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Bloemfontein, , South Africa

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Cape Town, , South Africa

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Durban, , South Africa

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eMkhomazi, , South Africa

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Pretoria, , South Africa

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Somerset West, , South Africa

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Soweto, , South Africa

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Vosloorus Ext 2, , South Africa

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Badalona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Countries

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United States Argentina Bulgaria Canada China Germany Hungary Italy Japan Lithuania Mexico Poland Romania Russia South Africa Spain

References

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Bareille P, Forth R, Imber V, Bondarenko I, Michaud A, Majorek-Olechowska B. Once-daily fluticasone furoate/vilanterol vs once-daily fluticasone furoate in patients with asthma aged 5 to 17 years. Ann Allergy Asthma Immunol. 2024 Nov;133(5):537-544.e4. doi: 10.1016/j.anai.2024.06.024. Epub 2024 Jun 25.

Reference Type BACKGROUND
PMID: 38936466 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-004086-87

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

107116

Identifier Type: -

Identifier Source: org_study_id

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