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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03207243




Registration number
NCT03207243
Ethics application status
Date submitted
29/06/2017
Date registered
2/07/2017
Date last updated
2/03/2020

Titles & IDs
Public title
Efficacy and Safety Study of GSK3772847 in Subjects With Moderately Severe Asthma
Scientific title
A Randomized, Double-blind, Parallel Group, Multicenter, Stratified Study Evaluating the Efficacy and Safety of Repeat Doses of GSK3772847 Compared With Placebo in Participants With Moderately Severe Asthma
Secondary ID [1] 0 0
2017-001072-34
Secondary ID [2] 0 0
207597
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK3772847
Treatment: Drugs - Placebo
Treatment: Drugs - Fluticasone propionate/salmeterol
Treatment: Drugs - Fluticasone propionate

Experimental: Subjects receiving GSK3772847 - Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and dose of FP was reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation.

Placebo Comparator: Subjects receiving placebo drug - Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and dose of FP was reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation.


Treatment: Drugs: GSK3772847
GSK3772847 10 mg/kg will be administered as IV infusion once every 4 weeks to randomized subjects.

Treatment: Drugs: Placebo
Placebo sterile normal saline will be administered as IV infusion once every 4 weeks to randomized subjects.

Treatment: Drugs: Fluticasone propionate/salmeterol
FP/Sal 500/50 mcg will be administered via inhalation route twice daily to all subjects.

Treatment: Drugs: Fluticasone propionate
FP 500, 250, 100 or 50 mcg will be administered via inhalation route twice daily to all subjects.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Loss of Asthma Control Over Weeks 0-16 - Loss of asthma control is defined as: Asthma Control Questionnaire (ACQ-5) score increase from Baseline >=0.5 point or pre-bronchodilator forced expiratory volume in 1 second (FEV1) decrease from baseline >7.5 % or inability to titrate inhaled corticosteroid or a clinically significant asthma exacerbation (requiring oral corticosteroid [OCS] and/or hospitalization). The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Baseline is defined as Day1. Percentage of participants experiencing loss of asthma control up to Week 16 has been presented. Modified Intent-to-Treat (Loss of Control) (mITT_LoC) population consisted of all randomized participants who took at least 1 dose of study treatment and if participants experienced loss of asthma control, they were analyzed according to actual treatment at time of loss of control.
Timepoint [1] 0 0
Up to Week 16
Secondary outcome [1] 0 0
Percentage of Participants With >=0.5 Point Asthma Control Questionnaire (ACQ-5) Score Increase From Baseline - The ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. A change of >=0.5 in score suggests a clinically important change in score. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment
Timepoint [1] 0 0
Baseline and up to Week 16
Secondary outcome [2] 0 0
Percentage of Participants Who Have Pre-bronchodilator FEV1 Decrease From Baseline >7.5 % - Pulmonary function is measured by FEV1. FEV1 is the amount of air expired in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. Baseline is defined as the latest available pre-dose assessment (Day 1). Decrease from Baseline >7.5 % in score suggests worsening of condition.
Timepoint [2] 0 0
Baseline and up to Week 16
Secondary outcome [3] 0 0
Percentage of Participants With Inability to Titrate Inhaled Corticosteroids (ICS) - Corticosteroid titration allows overall clinical evaluation of the participant's asthma status taking into account both lung function and symptom control. Inability to titrate inhaled corticosteroids indicates loss of asthma control.
Timepoint [3] 0 0
Up to Week 16
Secondary outcome [4] 0 0
Percentage of Participants With Clinically Significant Asthma Exacerbation - A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization.
Timepoint [4] 0 0
Up to Week 16
Secondary outcome [5] 0 0
Percentage of Participants With Loss of Asthma Control Over Weeks 0-6 - Loss of asthma control is defined as: ACQ-5 score increase from Baseline >=0.5 point or pre-bronchodilator FEV1 decrease from Baseline >7.5 % or inability to titrate inhaled corticosteroid or a clinically significant asthma exacerbation (requiring oral OCS and/or hospitalization). The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Baseline is defined as Day1. Percentage of participants experiencing loss of asthma control up to Week 6 has been presented.
Timepoint [5] 0 0
Up to Week 6
Secondary outcome [6] 0 0
Time to Loss of Asthma Control - Time to loss of asthma control was analyzed using Kaplan-Meier analysis. In this analysis, participants were either be counted as an event or they were censored. An event is defined as participants who experience loss of asthma control during the study. Censoring is defined as participants who discontinued investigational product for reasons other than loss of asthma control. The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Participants who didn't experience loss of asthma control were also censored at day 113.
Timepoint [6] 0 0
Up to Week 16
Secondary outcome [7] 0 0
Percentage of Participants With Clinically Significant Asthma Exacerbation or Inability to Titrate - A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization. Participants with clinically significant asthma exacerbation or inability to titrate FP indicated loss of asthma control.
Timepoint [7] 0 0
Up to Week 16
Secondary outcome [8] 0 0
Number of Participants Experiencing Asthma Related Hospitalization During the Study Period - Hospitalization is defined as an inpatient stay or least an overnight stay at the hospital or emergency ward for observation or other equivalent facility. Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [8] 0 0
Up to Week 16
Secondary outcome [9] 0 0
Rate Per 1000 Person-years of Participants With Hospitalization - An event is defined as an on-treatment asthma-related hospitalization or emergency room visit and participants can contribute to more than one event. Rate is calculated as number of events * 1000 divided by (number of participants in treatment group * mean treatment exposure in years). Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [9] 0 0
Up to Week 16
Secondary outcome [10] 0 0
Number of Hospitalizations or Emergency Room Visits Per Participants - The number of hospitalization or emergency room visit made by per participant due to loss of asthma control have been presented in category titles. Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [10] 0 0
Up to Week 16
Secondary outcome [11] 0 0
Change From Baseline in Asthma Control Questionnaire (ACQ-5) Total Score - ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath & wheeze) enquire about the frequency &/or severity of symptoms over the previous week. The response options range from zero (no impairment/limitation) to six (total impairment/limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [11] 0 0
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 16
Secondary outcome [12] 0 0
Percentage of Participants With <=-0.5 Point ACQ-5 Score Decrease From Baseline (Responder) - ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath & wheeze) enquire about the frequency &/or severity of symptoms over the previous week. The response options range from zero (no impairment/limitation) to six (total impairment/limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. A responder is defined as participants with change from Baseline of <= -0.5 point at given time point. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [12] 0 0
Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 16
Secondary outcome [13] 0 0
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score - SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on Health-related quality of life (HRQoL) of participants with Chronic Obstructive Pulmonary Disease (COPD). It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is defined as the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [13] 0 0
Baseline and Weeks 4, 8, 12 and 16
Secondary outcome [14] 0 0
Percentage of Participants With at Least a 4 Units Improvement From Baseline of St. George's Respiratory Questionnaire (SGRQ) - SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is defined as the latest available assessment prior to first dose (Day 1). A responder is defined as a change from Baseline of <= -4 at the given time point. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [14] 0 0
Baseline and Weeks 4, 8, 12 and 16
Secondary outcome [15] 0 0
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) - Pre-bronchodilator FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline is defined as the latest available assessment prior to first dose (Day 1) and change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [15] 0 0
Baseline and Weeks 2, 4, 6, 8, 10, 12, 14 and 16
Secondary outcome [16] 0 0
Change From Baseline in Mean Morning Peak Expiratory Flow (PEF) and Mean Evening PEF - PEF is maximum speed of expiration measured, using spirometer. The device was distributed to participants at Visit 1, to measure PEF twice-daily (morning upon waking & in the evening just before going to bed). Participants were encouraged to perform morning & evening PEF measurements before the use of any long-acting beta-agonists (LABAs) or rescue medication. Highest of 3 values were recorded in eDairy.Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants with at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Mean PEF was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16).Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment
Timepoint [16] 0 0
Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16.
Secondary outcome [17] 0 0
Change From Baseline in Mean Daytime Asthma Symptom Score Over Each Four Weeks of the 16 Week Treatment Period - Asthma symptoms experienced by participants during the day was recorded in e-Diary every evening before going to bed in form of scores on a 5-point rating scale. Scores ranged from 0=no daytime asthma symptoms to 4=very severe daytime asthma symptoms. Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants with at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. The mean asthma symptom score was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16). Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [17] 0 0
Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16
Secondary outcome [18] 0 0
Change From Baseline in Mean Daily Rescue Medication Use (Albuterol/Salbutamol) - The mean number of inhalation of rescue medication (albuterol/salbutamol) used to relieve symptoms immediately during the day and night was recorded in eDiary from Baseline until Week 16. Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants with at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. The mean rescue medication use was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16). Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [18] 0 0
Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16
Secondary outcome [19] 0 0
Change From Baseline in Percent Night-time Awakenings Due to Asthma Symptoms Requiring Rescue Medication Use - Participant captured night-time awakenings (yes/no) and use of rescue medication during these awakenings (yes/no) was recorded in e-Diary each morning. Percentage of night-time awakenings is calculated by number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data available*100. Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants having at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Night-time awakenings due to asthma symptoms requiring rescue medication was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16). Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [19] 0 0
Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16
Secondary outcome [20] 0 0
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) - FeNO was assessed as a measure of airway inflammation using a handheld electronic device. The measurements recorded were according to standardized procedures by the American Thoracic Society and the European Respiratory Society Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide. FeNO measurements were obtained prior to FEV1 assessments. Participants did not use their rescue medication for at least 6 hours before each FeNO assessment, unless essential for clinical need. Baseline is defined as the latest available assessment prior to first dose (Day 1). Percent change from Baseline is calculated as ratio to Baseline minus one and multiplied by 100. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.
Timepoint [20] 0 0
Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14 and 16
Secondary outcome [21] 0 0
Number of Participants Reporting Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) - A non-SAE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment were categorized as SAE.
Timepoint [21] 0 0
Up to Week 16
Secondary outcome [22] 0 0
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) - DBP and SBP were measured in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data for change from Baseline for post dose values have been presented.
Timepoint [22] 0 0
Baseline and Week 0 (Post-dose), Week1, Week 2, Week 4 (Pre and Post dose), Week 6, Week 8 (Pre and Post dose), Week 10, Week 12 (Pre and Post dose), Week 14, Week 16, Week 20, Week 24 and Week 28
Secondary outcome [23] 0 0
Change From Baseline in Pulse Rate (PR) - Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data for change from Baseline for post dose values have been presented.
Timepoint [23] 0 0
Baseline and Week 0 (Post-dose), Week1, Week 2, Week 4 (Pre and Post dose), Week 6, Week 8 (Pre and Post dose), Week 10, Week 12 (Pre and Post dose), Week 14, Week 16, Week 20, Week 24 and Week 28
Secondary outcome [24] 0 0
Change From Baseline Between Post-dose and Pre-dose in DBP and SBP - DBP and SBP was measured pre-dose and post-dose in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [24] 0 0
Baseline and Weeks 0, 4, 8 and 12
Secondary outcome [25] 0 0
Change From Baseline Between Post-dose and Pre-dose in Pulse Rate - Pulse rate was measured pre-dose and post-dose in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [25] 0 0
Baseline and Weeks 0, 4, 8 and 12
Secondary outcome [26] 0 0
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia [QTcF] Interval and RR Interval - Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures PR interval, QRS duration, uncorrected QT interval, QTcF interval and RR interval. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [26] 0 0
Baseline and Week 0 (Post-dose), Week 4 (Pre and Post dose), Week 8 (Pre and Post dose), Week 12 (Pre and Post dose) and Week 16
Secondary outcome [27] 0 0
Change From Baseline in ECG Heart Rate - Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures heart rate. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [27] 0 0
Baseline and Week 0 (Post-dose), Week 4 (Pre and Post dose), Week 8 (Pre and Post dose), Week 12 (Pre and Post dose) and Week 16
Secondary outcome [28] 0 0
Change From Baseline in QRS Axis - Triplicate 12-lead ECGs were recorded with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures QRS axis. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [28] 0 0
Baseline and Week 4 (Pre and Post dose), Week 8 (Pre and Post dose), Week 12 (Pre and Post dose) and Week 16
Secondary outcome [29] 0 0
Change Between Pre-dose and Post-dose of PR Interval, QRS Duration, Uncorrected QT Interval, QTcF Interval and RR Interval - Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures PR interval, QRS duration, uncorrected QT interval, QTcF interval and RR interval. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [29] 0 0
Baseline and Weeks 0, 4, 8 and 12
Secondary outcome [30] 0 0
Change Between Pre-dose and Post-dose of Heart Rate - Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures heart rate. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [30] 0 0
Baseline and Weeks 0, 4, 8 and 12
Secondary outcome [31] 0 0
Change Between Pre-dose and Post-dose of QRS Axis - Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures QRS axis. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [31] 0 0
Baseline and Weeks 0, 4, 8 and 12
Secondary outcome [32] 0 0
Change From Baseline in Maximum, Minimum and Average Changes in Heart Rate - Using a Holter monitor, maximum, minimum and average changes in heart rate was recorded at Baseline, Weeks 0, 4 and 12 through 24 hours. Participants with analyzable time of at least 16 hours were evaluated. Baseline is the value from the screening visit assessment. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [32] 0 0
Baseline and Weeks 0, 4 and 12
Secondary outcome [33] 0 0
Change From Baseline in Supraventricular Couplets, Supraventricular Ectopics, Supraventricular Runs, Supraventricular Singles, Ventricular Couplets, Ventricular Ectopics, Ventricular Runs, Ventricular Singles - Using a Holter monitor, supraventricular couplets, supraventricular ectopics, supraventricular runs, supraventricular singles, ventricular couplets, ventricular ectopics, ventricular runs, ventricular singles were recorded at Baseline, Weeks 0, 4 and 12 through 24 hours. Participants with analyzable time of at least 16 hours were evaluated. Baseline is the value from the screening visit assessment. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [33] 0 0
Baseline and Weeks 0, 4 and 12
Secondary outcome [34] 0 0
Change From Baseline in Clinical Chemistry Parameter: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Gamma- Glutamyl Transferase (GGT) and Creatine Kinase (CK) - Blood samples were collected for the analysis of clinical chemistry parameters including AST, ALT, ALP, GGT and CK at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [34] 0 0
Baseline and Weeks 2, 4, 8, 12, 16 and 28
Secondary outcome [35] 0 0
Change From Baseline in Clinical Chemistry Parameters: Glucose, Potassium, Sodium, Calcium, Phosphate, Chloride, Urea and Carbon Dioxide (CO2) - Blood samples were collected at given time points to assess clinical chemistry parameters including glucose, potassium, sodium, calcium, Phosphate, chloride, urea and CO2 levels. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [35] 0 0
Baseline and Weeks 2, 4, 8, 12, 16 and 28
Secondary outcome [36] 0 0
Change From Baseline in Clinical Chemistry Parameters: Creatinine, Total Bilirubin and Direct Bilirubin - Blood samples were collected for the analysis of clinical chemistry parameters including total bilirubin, creatinine and direct bilirubin at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [36] 0 0
Baseline and Weeks 2, 4, 8, 12, 16 and 28
Secondary outcome [37] 0 0
Change From Baseline in Clinical Chemistry Parameters: Total Protein and Albumin - Blood samples were collected at given time points to assess clinical chemistry parameters including total protein and albumin levels. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [37] 0 0
Baseline and Weeks 2, 4, 8, 12, 16 and 28
Secondary outcome [38] 0 0
Change From Baseline in Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets - Blood samples were collected at given time points to assess hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, leutrophils, monocytes, and platelets . Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [38] 0 0
Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [39] 0 0
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume - Blood samples were collected for the analysis of erythrocyte mean corpuscular volume at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [39] 0 0
Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [40] 0 0
Change From Baseline in Hematology Parameter: Erythrocytes - Blood samples were collected for the analysis of erythrocytes at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [40] 0 0
Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [41] 0 0
Change From Baseline in Hematology Parameter: Hemoglobin - Blood samples were collected for the analysis of hemoglobin level at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [41] 0 0
Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [42] 0 0
Change From Baseline in Hematology Parameter: Hematocrit Level - Blood samples were collected for the analysis of hematocrit at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [42] 0 0
Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [43] 0 0
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin - Blood samples were collected for the analysis of mean corpuscular hemoglobin at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [43] 0 0
Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [44] 0 0
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin Concentration - Blood samples were collected for the analysis of mean corpuscular hemoglobin concentration at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [44] 0 0
Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [45] 0 0
Change From Baseline in Hematology Parameter: Erythrocytes Distribution Width (%) - Blood samples were collected for the analysis of Erythrocytes Distribution Width (%) at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [45] 0 0
Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [46] 0 0
Change From Baseline in Cardiac Marker: N-Terminal ProB-type Natriuretic Peptide - Blood samples were collected for the analysis of N-Terminal ProB-type Natriuretic Peptide at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [46] 0 0
Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [47] 0 0
Change From Baseline in Cardiac Marker: Cardiac Troponin I - Blood samples were collected for the analysis of Troponin I at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Timepoint [47] 0 0
Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
Secondary outcome [48] 0 0
Number of Participants With Incidence and Titres of Anti- GSK3772847 Antibodies - Blood samples were collected at given time points and the presence of anti-GSK3772847 antibodies were assessed using a a tiered approach including a screening assay, a confirmation assay and calculation of titer. Data for participants who showed positive results for confirmation assay has been presented
Timepoint [48] 0 0
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and 28
Secondary outcome [49] 0 0
Serum Concentrations of GSK3772847 - Blood samples were collected at given time points to evaluate pharmacokinetics (PK) of GSK3772847 in participants with moderately severe asthma.
Timepoint [49] 0 0
Weeks 2, 4 (Pre-dose), 8 (Pre-dose), 12 (Pre-dose and Post-dose), 16, 20, 24 and 28
Secondary outcome [50] 0 0
Percent Change From Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration - Blood samples were collected at given time points to measure free soluble ST2 concentration. Baseline is defined as the latest available assessment prior to first dose (Day 1). Analysis was performed using mixed model repeated measures. Percent change from Baseline is calculated as ratio to Baseline minus 1 and multiplied by 100.
Timepoint [50] 0 0
Baseline and Week 4 (Pre-dose), Week 8 (Pre-dose), Week 12 (Pre-dose) and Week 16
Secondary outcome [51] 0 0
Percent Change From Baseline in Total Soluble ST2 Concentration - Blood samples were collected at given time points to measure total soluble ST2 concentration. Baseline is defined as the latest available assessment prior to first dose (Day 1). Analysis was performed using mixed model repeated measures. Percent change from Baseline is calculated as ratio to Baseline minus 1 and multiplied by 100.
Timepoint [51] 0 0
Baseline and Week 4 (Pre-dose), Week 8 (Pre-dose), Week 12 (Pre-dose) and Week 16

Eligibility
Key inclusion criteria
- Age: At least 18 years of age at the time of signing the informed consent.

- Males and females: A female subject is eligible to participate if she is not pregnant,
not breastfeeding, and at least one of the following conditions applies: Not a woman
of childbearing potential (WOCBP) OR A WOCBP who agrees to follow highly effective
contraceptive methods from 4 weeks prior to the first dose of study medication and
until at least 16 weeks after the last dose of study medication and completion of the
follow-up visit.

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

- A subject with a documented diagnosis of moderate severe asthma based on Global
Initiative for Asthma (GINA) 2016 Guidelines, whose asthma has been managed with
regular treatment of high dose ICS defined as FP 500 mcg twice daily (i.e. 1000 mcg
total daily dose) or equivalent, and LABA for at least 4 months. Additional therapy
with a leukotriene receptor antagonist (LTRA) is permissible.

- Airway reversibility of at least 12 percent and 200 milliliter (mL) in FEV1 at
Screening (Visit 1), or documented reversibility prior to Screening (Visit 1), or
documented history of bronchial hyper reactivity (e.g. fall in FEV1 from baseline of
more than or equal to 20percent with standard doses of methacholine or histamine, or
more than or equal to 15 percent with standardized hyperventilation, hypertonic saline
or mannitol challenge) from a bronchoprovocation study [e.g. methacholine challenge
prior to Screening (Visit 1)].

- ACQ-5 score more than or equal to 1.0 and less than 4.0 at Screening (Visit 1).

- Had at least one asthma exacerbation within 12 months prior to screening that required
treatment with systemic corticosteroid and/or hospitalization.

- All subjects must be able to replace their current Short-Acting Beta2-Agonists (SABA)
treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed, per
product label, for the duration of the study.

Randomization inclusion criteria:

- ACQ-5 score more than or equal to 1.0 and less than 4.0 at Visit 2.

- Compliance with completion of the Daily eDiary reporting defined as completion of all
questions/assessments on more than or equal to 4 of the last 7 days during the run-in
period.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Current smokers or former smokers with a smoking history more than or equal to 10 pack
years.

- Presence of a known pre-existing, clinically important respiratory conditions (e.g.
pneumonia, pneumothorax, atelectasis segmental or larger, pulmonary fibrotic disease,
bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive
pulmonary disease, or other respiratory abnormalities) other than asthma.

- A pre-bronchodilator FEV1 less than 50 percent predicted of normal value at Screening
(Visit 1).

- Subjects with a diagnosis of malignancy or in the process of investigation for a
malignancy. Subjects with carcinoma that have not been in complete remission for at
least 5 years. Subjects 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 subject has been considered cured by treatment.

- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
result at Screening (Visit 1) or within 3 months prior to first dose of study
treatment.

- Site investigators will be provided with ECG over-read conducted by a centralized
independent cardiologist, to assist in evaluation of subject eligibility.

- Weight: less than 50 kilograms (kg) and more than 150 kg.

- Regular use of systemic corticosteroids for conditions including asthma within 3
months prior to Screening (Visit 1).

- Subjects with high parasympathetic tone (e.g. trained athletes with baseline
bradycardia) or chronic conditions associated with parasympathetic surges (e.g.
migraines).

- Other conditions that could lead to elevated eosinophils such as hypereosinophilic
syndromes. Subjects with a known, pre-existing parasitic infestation within 6 months
prior to Screening (Visit 1).

- Clinically significant organic heart disease [e.g. Coronary artery disease (CAD), New
York Heart Association (NYHA) Class III/IV heart failure].

- Ongoing infections (i.e. not resolved within 7 days prior to Screening [Visit 1]) or
recurrent infections (i.e. requiring treatment for an identical diagnosis within 3
months) requiring systemic antibiotics Known, pre-existing parasitic infestations
within 6 months prior to Screening.

- A subject must not have any clinically significant, uncontrolled condition, or disease
state that, in the opinion of the investigator, would put the safety of the subject at
risk through study participation or would confound the interpretation of the efficacy
results if the condition/disease exacerbated during the study.

- A known immunodeficiency such as human immunodeficiency virus infection.

- Subjects with allergy or intolerance to a monoclonal antibody or biologic or to any
components of the formulation used in this study.

- Subjects with a history (or suspected history) of alcohol misuse or substance abuse
within 2 years prior to Screening (Visit 1).

- Subjects who are unable to follow study instructions such as visit schedule, dosing
directions, study eDiary completion, or use of a standard metered dose inhaler.
Subjects who have known evidence of lack of adherence to controller medication and/or
ability to follow physician's recommendations. Any infirmity, disability, or
geographic location that would limit compliance for scheduled visits.

- Subjects who have previously participated in a study of GSK3772847.

- Use of the prohibited medications is not permitted within the defined time intervals
prior to Screening (Visit 1) and throughout the study. Potential subjects should not
be washed out of their medication solely for the purpose on enrolling in the trial.

- A subject will not be eligible for this study if he/she is an immediate family member
of the participating investigator, sub investigator, study coordinator, or employee of
the participating investigator.

- In the opinion of the investigator, any subject who is unable to read and/or would not
be able to complete a diary card/questionnaire.

- Subjects 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.

Randomization exclusion criteria:

- Evidence of clinically significant abnormal laboratory tests during screening 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.

- Evidence of clinically significant abnormal ECG findings at Visit 2.

- An abnormal and significant finding from 24-hour Holter monitoring at Screening (Visit
1). Investigators will be provided with Holter reviews conducted by an independent
cardiologist to assist in evaluation of subject eligibility.

- Liver function at screening (Visit 1): ALT more than 2 x upper limit of normal (ULN)
and bilirubin more than 1.5xULN (isolated bilirubin more than 1.5xULN is acceptable if
bilirubin is fractionated and direct bilirubin less than 35 percent); Current or
chronic history of liver disease, or known hepatic or biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones).

- Subjects with ongoing asthma exacerbation at the time of Visit 2.

- A pre-bronchodilator FEV1 less than 50 percent predicted of normal value at Visit 2.

- Positive pregnancy test at Visit 0, Screening (Visit 1) or Visit 2.

- Ongoing or recurrent infections requiring systemic antibiotics.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Woodville South
Recruitment hospital [2] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [3] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [4] 0 0
GSK Investigational Site - Parkville
Recruitment postcode(s) [1] 0 0
5011 - Woodville South
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Canada
State/province [22] 0 0
Québec
Country [23] 0 0
Mexico
State/province [23] 0 0
Jalisco
Country [24] 0 0
Mexico
State/province [24] 0 0
Morelos
Country [25] 0 0
Mexico
State/province [25] 0 0
Nuevo León
Country [26] 0 0
Mexico
State/province [26] 0 0
Tabasco
Country [27] 0 0
Mexico
State/province [27] 0 0
Yucatán
Country [28] 0 0
Mexico
State/province [28] 0 0
Mexico City
Country [29] 0 0
Mexico
State/province [29] 0 0
México DF
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Chelyabinsk
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Kemerovo
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Saint Petersburg
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Saint-Petersburg
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Samara
Country [35] 0 0
Russian Federation
State/province [35] 0 0
St. Petersburg
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Tomsk
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Ulyanovsk
Country [38] 0 0
Ukraine
State/province [38] 0 0
Kyiv

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
GSK3772847, an anti-interleukin (IL)33 receptor monoclonal antibody, is a novel treatment for
asthma. This is a phase 2a study which aims to evaluate efficacy, safety, tolerability,
pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 in subjects with
moderately severe asthma. The study will be conducted in 4 phases including screening, run-in
phase, treatment phase and follow-up. In treatment phase, eligible subjects will be
randomized to receive either GSK3772847 or placebo administered via intravenous (IV) route
every 4 weeks in addition to open-label background therapy of fluticasone propionate/
salmeterol (FP/Sal) 500/50 micrograms (mcg) twice daily. During the treatment phase, the
background therapy will be switched to FP 500 mcg for 2 weeks and the dose of FP will be
reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation. The
total duration of study will be approximately 33 weeks and approximately 165 subjects with
moderately severe asthma who are maintained on high-dose of inhaled corticosteroids/
Long-Acting Beta-2-Agonists (ICS/LABA) will be randomized.
Trial website
https://clinicaltrials.gov/show/NCT03207243
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications