Clinical trial NCT02889809: Effects of a Orally Inhaled Fluticasone Furoate on Growth Velocity in Prepubertal, Paediatric Subjects With Asthma Over a Year
Official title: Study HZA114971, A Multicentre Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effects of a One-Year Regimen of Orally Inhaled Fluticasone Furoate 50 mcg Once Daily on Growth Velocity in Prepubertal, Paediatric Subjects With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Growth Velocity
Prepubertal
Asthma
Paediatric
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-09-07
Enrollment: 477
Sex: ALL
Minimum age (years): 5
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is a regulatory requirement to evaluate the extent of reduction (if any) of growth velocity associated with inhaled corticosteroid (ICS) containing products that are to be administered to children, and to this end there is Food and Drug Administration (FDA) regulatory guidance. This is a randomised, single-blind (run-in period)/double-blind (treatment period), parallel group, placebo controlled, multicentre study to assess the effect of once daily (OD) inhaled fluticasone furoate (FF) 50 microgram (mcg) on growth velocity in prepubertal asthmatic children on a background therapy of open-label montelukast. This study will be conducted over a total duration of approximately 76 weeks: 16-week run-in period (single-blind placebo inhaler), 52-week double-blind treatment period (inhaled FF 50 mcg /placebo administered OD in the morning for 52 weeks) and 8-week follow-up period. The purpose of the study is to evaluate the magnitude of effect (with a level of precision) on growth velocity of prepubertal asthmatic paediatric subjects (aged 5 to \<9 years) following administration of OD inhaled FF 50 mcg for one year. This study fulfills European Union (EU) and United States (US) regulatory requirements for the evaluation of potential growth suppression in children.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects.
* Age: Males between 5 and \<9 years old; Females between 5 and \<8 years old.
* Subjects must be pre-pubertal (Tanner Stage 1).
* Height centile between 3% and 97% based on local growth charts.
* Subjects with body weight and body mass index that is between 3rd and 97th centile based on the United State (US) Centres for Disease Control and Prevention (CDC) standard statistics or any local standards outside the US.
* A documented history of symptoms consistent with a diagnosis of asthma for at least 6 months prior to Visit 1.
* A pre-bronchodilatory forced expiratory flow in 1 second (FEV1) at Visit 1 (Screening) of between \>=60% to \<=95% predicted. There should be no short acting beta 2 agonist (SABA) use within 4 hours of this measurement.
* Able to replace their current SABA treatment with study supplied rescue albuterol/salbutamol provided at Visit 1 for use as needed for the duration of the study.
* A childhood asthma control test (cACT) score of \>19.
* Subjects should have required at least one course of corticosteroid for their asthma (inhaled or oral) in the past year.
* There must be no ICS use within 6 weeks of Visit 1 (Screening).
* There must be no oral corticosteroids use within 12 weeks of Visit 1 (Screening).
* Using one or more of the following asthma therapies prior to entry into the study:

Short acting beta-agonist (SABA) inhaler alone (example given \[e.g.\] salbutamol) on an as needed basis and/or regular non-ICS controller medications for asthma (e.g. cromones or leukotriene receptor antagonists).

- Written informed consent from at least one 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 local requirement. The study investigator is accountable for determining a child's capacity to assent for 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 they must comply with study medication administration regimens and study assessments including recording of symptom scores and rescue albuterol/salbutamol use, attending all study visits, and being accessible by telephone.

Exclusion Criteria:

* Growth Criteria: Any previous or current condition that affects growth, including sleep disorders, endocrine disorders, skeletal dysplasia, Turner and Noonan syndromes, Marfan, Beckwith-Wiedeman and Sotos syndromes, Klinefelter's syndrome, coeliac disease, inflammatory bowel diseases and renal failure or any significant abnormality or medical condition that is identified at the screening medical assessment (including serious psychological disorder) that is likely to interfere with the conduct of the study.
* Subjects with premature adrenarche.
* A child who is unable to stand, or who finds standing difficult due to illness or physical disabilities should be excluded.
* Disease Criteria: Subjects with a history of asthma exacerbation requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or use of a depot corticosteroid injection within 3 months or those requiring hospitalisation for asthma (within 6 months) prior to screening.
* Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and 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 candidiasis at Visit 1 (Screening).
* Any significant abnormality or medical condition identified at the screening medical assessment that in the Investigator's opinion, preclude entry into the study due to risk to the subject or that may interfere with the outcome of the study.
* General: Prior use of any medication or treatment that might affect growth including, but not limited to: amphetamines, anticonvulsants, biphosphonates, calcitonin, calcitriol, erythropoietin, growth hormone, methylphenidate, phosphate binders, antithyroid drugs (e.g., Methimazole) or thyroid hormone.
* Use of any of the prohibited medications listed in the study protocol.
* Hypersensitivity: Known hypersensitivity to corticosteroids, leukotrienes, or any excipients in the ELLIPTA (ELLIPTA is a Glaxosmithkline owned trademark for dry powder inhaler) inhaler and study tablets.
* Milk Protein Allergy: History of severe milk protein allergy.
* The subject has 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, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
* Children who are 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 known or suspected 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 subject during the study; compliance of subject with study medication and study procedures (e.g. 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.

Primary outcomes:
measure: Growth Velocity (Centimeter Per Year) Over the Double-blind Treatment Period, as Determined by Stadiometry
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Percentage of Participants Below the Third Percentile of Growth Velocity During Double-blind Treatment Period
timeFrame: Up to 52 weeks
measure: Percentage of Participants With Change in Growth Velocity Quartiles From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 28[Visit 12] up to and including Week 52 [Visit 18])
measure: Growth Velocity Over the First 12 Weeks of Double-blind Treatment Period
timeFrame: Up to 12 weeks (Visit 8) of double-blind treatment period
measure: Change in Height Standard Deviation Scores (SDS) From Baseline to Endpoint
timeFrame: Baseline (Week 0 [Visit 5]) and up to Endpoint (Week 52 [Visit 18])
measure: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 76 weeks
measure: Number of Participants With On-treatment Asthma Exacerbations Over Double-blind Treatment Period
timeFrame: Up to 52 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Homestead
country: United States
facility: GSK Investigational Site
state: Florida
city: Loxahatchee Groves
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Saint Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Gainesville
country: United States
facility: GSK Investigational Site
state: Georgia
city: Ypsilanti
country: United States
facility: GSK Investigational Site
state: Michigan
city: Bellevue
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Waco
country: United States
facility: GSK Investigational Site
state: Texas
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Lanús
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdansk-Wrzeszcz
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Skarzysko-Kamienna
country: Poland
facility: GSK Investigational Site
city: Szczecin
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: ClujNapoca
country: Romania
facility: GSK Investigational Site
city: Sangiorgiu De Mures
country: Romania
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St.Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Middelburg
country: South Africa
facility: GSK Investigational Site
state: Mpumalanga
city: Bellville
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bareille P, Imber V, Crawford J, Majorek-Olechowska B, Karam-Absi Z, Stone S, Birk R. A multicenter randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effects of a 1-year regimen of orally inhaled fluticasone furoate 50 microg once daily on growth velocity in prepubertal, pediatric participants with well-controlled asthma. Pediatr Pulmonol. 2023 Dec;58(12):3487-3497. doi: 10.1002/ppul.26679. Epub 2023 Sep 20.