Efficacy and Safety of Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) in Chinese Participants With Inadequately Controlled Asthma

Asthma Clinical Trial

Official title:

A Phase III, 12 Week, Randomized, Double-blind, 4 Arm Parallel Group Bridging Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Combination FF/UMEC/VI Once-daily Via a Dry Powder Inhaler With Dual Combination of FF/VI, Administered in Chinese Participants With Inadequately Controlled Asthma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04937387
• Other study ID #: 214263
• Status: Recruiting
• Phase: Phase 3
• Start date: July 29, 2021
• Est. completion date: September 30, 2024

Study information

• Verified date: October 2022
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to evaluate the efficacy, safety and tolerability of FF/UMEC/VI compared with FF/VI via ELLIPTA® inhaler in Chinese participants with inadequately controlled asthma. ELLIPTA is a registered trademark of GlaxoSmithKline group of companies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 356
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Participant must be 18 years or older at the time of signing the informed consent.

• Documented history asthma diagnosis as defined by the Global Initiative for Asthma (GINA) at least one year prior to Visit 0.

• Participants with inadequately controlled asthma (ACQ-6 score >=1.5) despite Inhaled Corticosteroids/Long-Acting Beta-2-Agonists (ICS/LABA) maintenance therapy at Visit 1.

• Participants who require daily ICS/LABA for at least 12 weeks prior to Visit 0 with no changes to maintenance asthma medications during the 6 weeks immediately prior to Visit 0 (including no changes to a stable total dose of ICS of greater than [>]250 micrograms (mcg) per day fluticasone propionate [FP, or equivalent]).

• A best pre-bronchodilator morning (AM) FEV1 >=30 percent (%) and less than (<) 85% of the predicted normal value at Visit 1. Predicted values will be based upon the European Respiratory Society (ERS) Global Lung Function Initiative.

• Airway reversibility defined as >=12% and >=200 milliliters (mL) increase in FEV1 between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol at Visit 1.

• All participants must be able to replace their current Short-Acting Beta-2-Agonists (SABA) inhaler with albuterol/salbutamol aerosol inhaler at Visit 1 as needed for the duration of the study. Participants must be judged capable of withholding albuterol/salbutamol for at least 6 hours prior to study visits.

• Male or female participants following contraceptive/barrier requirements and it should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) or a woman of childbearing potential (WOCBP) who agrees to follow the contraceptive guidance during the study.

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

• Chest X-ray documented pneumonia in the 6 weeks prior to Visit 1.

• Any asthma exacerbation requiring a change in maintenance asthma therapy in the 6 weeks prior to Visit 1.

• Participants with the diagnosis of chronic obstructive pulmonary disease, as per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, including all of the following:

1. History of exposure to risk factors (especially tobacco smoke, occupational dusts and chemicals, smoke from home cooking and heating fuels).

2. A post-albuterol/salbutamol FEV1/Forced Vital Capacity (FVC) ratio of <0.70 and a post-albuterol/salbutamol FEV1 of less than or equal to (<=)70% of predicted normal values.

3. Onset of disease >=40 years of age.

• Participants with current evidence of pneumonia, active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases or abnormalities other than asthma.

• Immune suppression (e.g., Human Immunodeficiency virus [HIV], Lupus) or other risk factors for pneumonia (e.g., neurological disorders affecting control of the upper airway, such as Parkinson's Disease, Myasthenia Gravis). Participants at potentially high risk (e.g., very low Body Mass Index [BMI], severely malnourished, or very low FEV1) will only be included at the discretion of the Investigator.

• Participants with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.

• Unstable liver disease as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Clinically significant Electrocardiogram (ECG) abnormality: Evidence of a clinically significant abnormality in the 12-lead ECG performed during screening. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the participant's medical history and exclude participants who would be at undue risk by participating in the trial. An abnormal and clinically significant finding is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following:

1. Atrial Fibrillation with rapid ventricular rate >120 beats per minute (bpm).

2. Sustained or non-sustained ventricular tachycardia.

3. Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted).

4. QT interval corrected for heart rate by Fridericia's formula (QTcF) >=500 milliseconds (msec) in participants with QRS <120 msec and QTcF >=530 msec in participants with QRS >=120 msec.

• Participants with any of the following at Screening (Visit 1):

1. Myocardial infarction or unstable angina in the last 6 months.

2. Unstable or life-threatening cardiac arrhythmia requiring intervention in the last 3 months.

3. New York Heart Association (NYHA) Class IV Heart failure [American Heart Association, 2016].

• Participants with a medical condition such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy or bladder neck obstruction should only be included if in the opinion of the Investigator the benefit outweighs the risk and that the condition would not contraindicate study participation.

• Participants with carcinoma that has not been in complete remission for at least 5 years. Participants who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the participant has been considered cured by treatment.

• Participants with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.

• Participants who are medically unable to withhold their albuterol/salbutamol for the 6-hour period required prior to spirometry testing at each study visit.

• Participants who are:

1. Current smokers (defined as participants who have used inhaled tobacco products within the 12 months prior to Visit 1, e.g. cigarettes, electronic-cigarettes/vaping, cigars or pipe tobacco).

2. Former smokers with a smoking history of >=10 pack years (e.g. >=20 cigarettes per day for 10 years).

• Participants with a known or suspected history of alcohol or drug abuse within the last 2 years.

• A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate.

• Participants at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

• Study Investigators, sub-Investigators, study coordinators, employees of a participating Investigator or study site, or immediate family members of the aforementioned that is involved with this study.

• In the opinion of the Investigator, any participant who is unable to read and/or would not be able to complete study related materials.

Inclusion criteria for randomization:

• Participants with inadequately controlled asthma (ACQ-6 score >=1.5) at Visit 2.

• A best pre-bronchodilator morning (AM) FEV1 >=30% and <90% of the predicted normal value at Visit 2. Predicted values will be based upon the ERS Global Lung Function Initiative (Quanjer).

• Liver function tests at Visit 1:

1. Alanine aminotransferase (ALT) <2 times upper limit of normal (ULN).

2. Alkaline phosphatase <=1.5 times ULN.

3. Bilirubin <=1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Compliance with completion of the Electronic diary reporting defined as completion of all questions/assessment on >=4 of the last 7 days during the run-in period.

Exclusion criteria for randomization:

• 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 participant's asthma status or the participant's ability to participate in the study.

• Evidence of a severe exacerbation during screening or the run-in period, defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.

• Changes in asthma medication (excluding run-in medication and albuterol/salbutamol inhalation aerosol provided at Visit 1).

• Evidence of clinically significant abnormal laboratory tests during screening or run-in which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• FF/VI
FF/VI will be administered.
• FF/UMEC/VI
FF/UMEC/VI will be administered.

Device:
• ELLIPTA
FF/UMEC/VI and FF/VI will be administered via ELLIPTA inhaler.

Locations

Country	Name	City	State
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Fuzhou
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guilin	Guangxi
China	GSK Investigational Site	Haikou	Hainan
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hohhot	Inner Mongolia
China	GSK Investigational Site	Huhhot	Inner Mongolia
China	GSK Investigational Site	Jiangmen	Guangdong
China	GSK Investigational Site	Jinan	Shandong
China	GSK Investigational Site	Kunming
China	GSK Investigational Site	Lanzhou	Gansu
China	GSK Investigational Site	Nanchang
China	GSK Investigational Site	Qingdao	Shandong
China	GSK Investigational Site	Qingyuan	Guangdong
China	GSK Investigational Site	Qinhuangdao	Hebei
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shen Zhen	Guangdong
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenzhen	Guangdong
China	GSK Investigational Site	Shijiazhuang	Hebei
China	GSK Investigational Site	Taiyuan	Shanxi
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Urumqi	Xinjiang
China	GSK Investigational Site	Wenzhou	Zhejiang
China	GSK Investigational Site	Wuxi	Jiangsu
China	GSK Investigational Site	Xiamen	Fujian
China	GSK Investigational Site	Xian	Shaanxi
China	GSK Investigational Site	Yinchuan	Ningxia
China	GSK Investigational Site	Zhanjiang	Guangdong
China	GSK Investigational Site	Zhanjiang	Guangdong
China	GSK Investigational Site	Zhengzhou
China	GSK Investigational Site	Zhongshan	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohorts 1 and 2: Change from Baseline in trough Forced expiratory volume in 1 second (FEV1) (Liters)	FEV1 will be measured using spirometry.	Baseline and at Week 12
Secondary	Cohort 3 and 4: Change from Baseline in trough FEV1 (Liters)	FEV1 will be measured using spirometry.	Baseline and at Week 12
Secondary	Cohorts 1, 2 , 3 and 4: Change from Baseline in Asthma Control Questionnaire (7 items) (ACQ-7) (Scores on a scale)	ACQ-7 is a questionnaire used to assess the asthma control. Six attributes are measured with a participant-completed questionnaire assessing nocturnal awakening, waking in the morning, activity limitation, shortness of breath, wheeze and rescue medication use and the seventh attribute measures lung function. A score of less than or equal to (<=)0.75 indicates well-controlled asthma and a score greater than or equal to (>=)1.5 indicates poorly controlled asthma. A change of 0.5 in score suggests a clinically important change in score. Higher score indicates poor asthma control and lower score indicates well-controlled asthma.	Baseline and at Week 12