Open-label, Prospective, Crossover, Proof-of-concept Study to Evaluate the Effect of Triple Therapy With Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrrolate (BDP/FF/G) Via pMDI Compared With Non-extrafine Fluticasone Furoate/Umeclidinium/Vilanterol (FluF/UMEC/VI) Via DPI on Lung Ventilation and Clinical Outcomes in Subjects With Moderate to Severe Asthma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Evaluate the effect of extrafine beclomethasone dipropionate/formoterol fumarate /glycopyrrolate compared with non-extrafine fluticasone furoate/ umeclidinium/vilanterol on ventilation defect percentage utilizing 129Xenon MRI.
研究概览
简要总结
The purpose of the study is to enroll participants with uncontrolled asthma to evaluate the large and small airways and drug delivery utilizing two study drugs:
- Beclometasone dipropionate/Formoterol fumarate dihydrate/Glycopyrronium bromide (BDP/FF/G) or Trimbow
- Fluticasone furoate/Umeclidinium/Vilanterol (FluF/UMEC/VI ) or Trelegy Ellipta
详细描述
The study will comprise of 5 visits. A screening visit (V1, Week -2), with baseline assessment. At the randomization visit (V2, Week 0), patients will be randomized in a 1:1 ratio to receive one of the following treatments for 8 weeks:
- BDP/FF/G 100/6/12.5 mcg pMDI, two inhalations twice-daily
- FluF/UMEC/VI 100/62.5/25 mcg DPI, one inhalation once-daily
A subsequent visit will be performed at 8 weeks (V3), where participants will undergo spirometry, oscillometry, and imaging. Participants will then stop the assigned treatment and undergo a washout period of 4 weeks using an unrelated maintenance ICS/LABA combination inhaler.
Following the washout period, at the next visit (V4, Week 12) participants will then be crossed over to the other treatment they did not receive at randomization.
At the final visit (V5, Week 20), patients will once again undergo spirometry, oscillometry, and imaging. In the event of premature study discontinuation, an early termination (ET) visit will be conducted and the Investigator must fill in the "Study Termination" page in the eCRF, reporting the main reason for withdrawal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject's written informed consent obtained prior to any study-related procedure.
- •Patients aged ≥ 18 and ≤ 75 years
- •Confirmed diagnosis of asthma (patients must have a documented history of asthma for at least 1 year with diagnosis before the age of 40 and/or pre-bronchodilator FEV1 between 50-80% of their predicted normal value, after appropriate washout from bronchodilators)
- •Symptomatic on ICS/LABA treatment with ACT <20
- •No exacerbations in the past 3 months requiring treatment with systemic corticosteroids or emergency department visit/ in-patient hospitalization
- •The ability to be trained and correctly use a pressurized Meter Dose Inhaler (pMDI) and Dry Powder Inhaler (DPI)
- •To have a cooperative attitude and the ability to perform the required outcomes measurements (e.g. spirometry maneuvers in sitting and supine position) and the ability to understand the risks involved
- •WOCBP fulfilling one of the following criteria:
- •WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or
- •WOCBP with physician confirmed non-fertile male partners (contraception is not required in this case).
- •Female patients of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile, e.g. amenorrheic for ≥12 consecutive months without alternative medical cause). Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges).
排除标准
- •Pregnant or lactating female
- •Patients who had an exacerbation, defined as a sustained and acute deterioration of subject's symptoms and signs (dyspnea, cough and/or sputum production/purulence) that was either moderate, i.e. require treatment with systemic (oral/IV/IM) corticosteroids and/or antibiotics, or severe, i.e. require hospitalization, if their associated treatment/hospitalization occurred within 3 months prior to V1
- •Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake
- •History of near fatal asthma or of a past hospitalization for asthma in intensive care unit which, in the judgement of the Investigator, may have placed the patient at undue risk
- •Patients using systemic corticosteroid medication in the 4 weeks or slow-release corticosteroids in the 12 weeks, prior to screening
- •Patients who suffer from COPD as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) document
- •History of a diagnosis of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which may have interfered with study evaluations
- •Current smokers or current use of electronic cigarettes or ex-smokers with total cumulative exposure equal or more than 10 pack-years or having stopped smoking one year or less prior to screening visit
- •Patients who had clinically significant cardiovascular condition according to investigator's judgement, such as but not limited to: congestive heart failure (NYHA class >2), acute ischemic heart disease in the last year prior to study screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained meant lasting more than 30 seconds or ending only with external action, or led to hemodynamic collapse; non-sustained meant >3 beats <30 seconds, and or ending spontaneously, and or asymptomatic), high degree impulse conduction blocks (>2nd degree atrioventricular block type 2). Similarly, patients affected by persistent, long standing or paroxysmal AF were not considered for enrollment
- •Patients who are unable to undergo imaging procedures for CT scans or MRI or demonstrate intolerance to Xenon gas
- •Patients who have participated in a recent therapeutic trial (within past 6 months)
- •Patients who have a milk protein allergy
研究组 & 干预措施
Randomized beclomethasone dipropionate/formoterol fumarate /glycopyrrolate
For this randomized arm, Trimbow pMDI (BDP/FF/G 100/6/12.5 mcg), will be administered as two inhalations twice-daily 8 weeks following randomization.
干预措施: Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrrolate pMDI (Drug)
Randomized fluticasone furoate/ umeclidinium/vilanterol
For this randomized arm, Trelegy DPI (FluF/UMEC/VI 100/62.5/25 mcg), will be administered as one inhalation once daily for 8 weeks following randomization. .
干预措施: Fluticasone Furoate/Umeclidinium/Vilanterol 100 MCG/1 ACTUATION-62.5 MCG/1 ACTUATION-25 MCG/1 ACTUATION Inhalation Powder (Drug)
Cross-Over beclomethasone dipropionate/formoterol fumarate /glycopyrrolate
Following the washout period, participants that were randomized to receive Trelegy DPI (FluF/UMEC/VI 100/62.5/25 mcg) will be crossed over to receive Trimbow pMDI ( BDP/FF/G 100/6/12.5 mcg) for 8 weeks.
干预措施: Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrrolate pMDI (Drug)
Cross-Over fluticasone furoate/ umeclidinium/vilanterol
Following the washout period, participants that were randomized to receive Trimbow pMDI( BDP/FF/G 100/6/12.5 mcg) will be crossed over to receive Trelegy DPI (FluF/UMEC/VI 100/62.5/25 mcg) for 8 weeks.
干预措施: Fluticasone Furoate/Umeclidinium/Vilanterol 100 MCG/1 ACTUATION-62.5 MCG/1 ACTUATION-25 MCG/1 ACTUATION Inhalation Powder (Drug)
Wash-Out
Following the 8-week treatment period, participants will be placed on an ICS/LABA therapy unrelated to study medications during a 4-week wash-out period prior to cross-over.
结局指标
主要结局
Evaluate the effect of extrafine beclomethasone dipropionate/formoterol fumarate /glycopyrrolate compared with non-extrafine fluticasone furoate/ umeclidinium/vilanterol on ventilation defect percentage utilizing 129Xenon MRI.
时间窗: 8 weeks
Assess pre-post intervention ventilation defect percentage
次要结局
- Investigating the association of small airways deposition on lung function(8 weeks)
- Understanding the impact on asthma control using the Asthma Control Test(8 Weeks)
研究者
Surya P Bhatt
MD, MSPH
University of Alabama at Birmingham