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

ID: NCT03248128
Status: Recruiting
Phase: Phase 3
Start Date: October 20, 2017
First Submitted: August 09, 2017
Last Updated: February 22, 2018
Results: N/A
Organization: GlaxoSmithKline
Sponsors & Collaborators: GlaxoSmithKline
Location: Canada, Germany, Italy, Spain, United States
Conditions: Asthma
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Study Description

Brief Summary

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

Condition or disease Intervention/treatment Phase

Asthma

Drug: FF/VI via ELLIPTA DPI
Other Names
Drug: FF via ELLIPTA DPI
Other Names
Phase 3

Tracking Information

First Submitted DateAugust 09, 2017
Last Update Posted DateFebruary 22, 2018
Actual Start DateOctober 20, 2017
Anticipated Completion DateOctober 31, 2020
Actual Primary Completion DateOctober 31, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Cohort A and B: Weighted mean forced expiratory volume in 1 second (FEV1) (0-4 hours) at Week 12 [Time Frame: Week 12]

    Pulmonary function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 will be measured using a standardized calibrated spirometer prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use.

  • Cohort A: Change from Baseline, in pre-dose (i.e. trough) morning peak expiratory flow (PEF) averaged over weeks 1-12 of the treatment period [Time Frame: Baseline and up to Week 12]

    PEF is defined as the maximum speed of expiration of a person. PEF will be measured using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three measurements will be recorded in the daily diary.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Cohort A: Weighted mean of FEV1 (0-4 hours) at Week 12 [Time Frame: Week 12]

    Pulmonary function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 will be measured using a standardized calibrated spirometer prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use.

  • Cohort A and B: Change from Baseline, in pre-dose (i.e. trough) morning PEF averaged over weeks 1-12 of the treatment period [Time Frame: Baseline and up to Week 12]

    PEF is defined as the maximum speed of expiration of a person. PEF will be measured using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three measurements will be recorded in the daily diary.

  • Cohort A and B: Change from Baseline in the percentage of rescue-free 24-hour periods over weeks 1-12 of the treatment period [Time Frame: Baseline and up to Week 12]

    The number of inhalations of rescue albuterol/salbutamol aerosol used during the day and night will be recorded in a daily electronic diary. A 24-hour period in which the response of subjects to both the morning and evening assessments indicated no use of rescue medication will be considered as 'rescue free'.

  • Cohort A and B: Change from Baseline in the percentage of symptom-free 24-hour periods over weeks 1-12 of the treatment period [Time Frame: Baseline and up to Week 12]

    The symptom-free days will be recorded in a daily electronic diary every day in the morning and evening before taking any rescue or study medication and before the PEF measurement. A 24-hour period in which the response of subjects to both the morning and evening assessments indicated no symptoms will be considered as 'symptom free'.

  • Cohort A and B: Change from Baseline in morning (ante meridiem [AM]) FEV1 at Week 12 [Time Frame: Baseline and at Week 12]

    Pulmonary function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Morning FEV1 will be measured using a standardized calibrated spirometer prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use.

  • Cohort A and B: Change from Baseline in asthma control questionnaire (ACQ-5) at Week 24 [Time Frame: Baseline and at Week 24]

    The ACQ-5 is a five-item questionnaire, which includes five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze). The questions will enquire about the frequency and/or severity of symptoms over the previous week and will be self-completed by the subjects. The response options for all these questions will consist of a scale ranging from 0 (no impairment/limitation) to 6 (total impairment/ limitation). A score of <0.75 indicates well-controlled asthma and a score >=1.5 indicates poorly controlled asthma. A change of >=0.5 in score suggests a clinically important change in score.

  • Cohort A and B: Number of subjects with incidence of exacerbations over the 24-Week treatment period [Time Frame: Up to Week 24]

    An exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or a single depot corticosteroid injection or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Information regarding asthma exacerbations will be collected and recorded over the specified period.

  • Cohort A and B: Number of subjects with adverse events (AEs), serious adverse events (SAEs) [Time Frame: Up to Week 25]

    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

  • Cohort A and B: Number of subjects with abnormal electrocardiogram (ECG) findings [Time Frame: Up to Week 24]

    A single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected (QTc).

  • Cohort A and B:Number of subjects with abnormal fasting blood glucose levels [Time Frame: Up to Week 24]

    Blood samples will be collected for evaluation of fasting blood glucose pre- and post-treatment.

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleSafety and Efficacy Study of Fluticasone Furoate/Vilanterol (FF/VI) Fixed Dose Combination (FDC) Compared to FF Alone in Subjects With Asthma
Official TitleA 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
Brief Summary

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

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
870
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Asthma
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: 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).

Other Names
Drug: FF via ELLIPTA DPI

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

Other Names
Study Groups/Cohorts
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.

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.

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.

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.

Study Arms
Active Comparator 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.
Drug : FF via ELLIPTA DPI
ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).

Active Comparator 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.
Drug : FF via ELLIPTA DPI
ELLIPTA DPI inhaler will contain a single blister strip of FF (50 or 100 mcg).

Experimental 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.
Drug : 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).

Experimental 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.
Drug : 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).

Arm Intervention/Treatment
Active Comparator 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.
Drug : FF via ELLIPTA DPI
Active Comparator 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.
Drug : FF via ELLIPTA DPI
Experimental 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.
Drug : FF/VI via ELLIPTA DPI
Experimental 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.
Drug : FF/VI via ELLIPTA DPI

Recruitment Information

Recruitment Status:Recruiting
Enrollment870
Completion DateOctober 31, 2020
Eligibility 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.
GenderAll
Age5 Years to 17 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Canada
Germany
Italy
Spain
United States

Administrative Information

NCT Number:NCT03248128
Other Study ID Numbers
107116
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
GlaxoSmithKline
Collaborators
Not Available
Investigators
Study Director
GSK Clinical Trials
GlaxoSmithKline