A Phase 2 interventional study of GSK3772847 and Placebo in Asthma, sponsored by GlaxoSmithKline. Completed at 64 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-02.
Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment
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.
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This study's enrollment of 165 is above the median of 83 across 2,752 interventional studies indexed under Asthma.
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Randomization inclusion criteria:
Exclusion Criteria:
Randomization exclusion criteria:
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.
Drug: GSK3772847 · Drug: Fluticasone propionate/salmeterol · Drug: Fluticasone propionate
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.
Drug: Placebo · Drug: Fluticasone propionate/salmeterol · Drug: Fluticasone propionate
GSK3772847 10 mg/kg will be administered as IV infusion once every 4 weeks to randomized subjects.
Placebo sterile normal saline will be administered as IV infusion once every 4 weeks to randomized subjects.
FP/Sal 500/50 mcg will be administered via inhalation route twice daily to all subjects.
FP 500, 250, 100 or 50 mcg will be administered via inhalation route twice daily to all subjects.
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.
Time frame: Up to Week 16
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
Time frame: Baseline and up to Week 16
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.
Time frame: Baseline and up to Week 16
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.
Time frame: Up to Week 16
Percentage of Participants With Clinically Significant Asthma Exacerbation
A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization.
Time frame: Up to Week 16
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.
Time frame: Up to Week 6
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.
Time frame: Up to Week 16
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.
Time frame: Up to Week 16
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.
Time frame: Up to Week 16
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.
Time frame: Up to Week 16
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.
Time frame: Up to Week 16
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.
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 16
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.
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 16
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.
Time frame: Baseline and Weeks 4, 8, 12 and 16
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.
Time frame: Baseline and Weeks 4, 8, 12 and 16
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.
Time frame: Baseline and Weeks 2, 4, 6, 8, 10, 12, 14 and 16
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
Time frame: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16.
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.
Time frame: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16
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.
Time frame: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16
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.
Time frame: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14 and 16
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.
Time frame: Up to Week 16
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Baseline and Weeks 0, 4, 8 and 12
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.
Time frame: Baseline and Weeks 0, 4, 8 and 12
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Baseline and Week 4 (Pre and Post dose), Week 8 (Pre and Post dose), Week 12 (Pre and Post dose) and Week 16
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.
Time frame: Baseline and Weeks 0, 4, 8 and 12
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.
Time frame: Baseline and Weeks 0, 4, 8 and 12
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.
Time frame: Baseline and Weeks 0, 4, 8 and 12
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.
Time frame: Baseline and Weeks 0, 4 and 12
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.
Time frame: Baseline and Weeks 0, 4 and 12
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.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16 and 28
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.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16 and 28
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.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16 and 28
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.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16 and 28
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.
Time frame: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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.
Time frame: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28
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
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and 28
Serum Concentrations of GSK3772847
Blood samples were collected at given time points to evaluate pharmacokinetics (PK) of GSK3772847 in participants with moderately severe asthma.
Time frame: Weeks 2, 4 (Pre-dose), 8 (Pre-dose), 12 (Pre-dose and Post-dose), 16, 20, 24 and 28
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.
Time frame: Baseline and Week 4 (Pre-dose), Week 8 (Pre-dose), Week 12 (Pre-dose) and Week 16
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.
Time frame: Baseline and Week 4 (Pre-dose), Week 8 (Pre-dose), Week 12 (Pre-dose) and Week 16
This was a randomized, double-blind, placebo-controlled, parallel-group multicenter study to assess the efficacy, safety and tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 in participants with moderately severe asthma.
| Milestone | Placebo | GSK3772847 |
|---|---|---|
| Started | 82 | 83 |
| Completed | 23 | 39 |
| Not completed | 59 | 44 |
| Withdrew: Adverse event | 2 | 2 |
| Withdrew: Loss of asthma control | 47 | 31 |
| Withdrew: Withdrawal by subject | 2 | 4 |
| Withdrew: Physician decision | 1 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Protocol specified withdrawal criteria | 7 | 2 |
| Withdrew: Protocol violation | 0 | 3 |
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.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Percentage of Participants With Loss of Asthma Control Over Weeks 0-16 | 81 | 67 |
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
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Percentage of Participants With >=0.5 Point Asthma Control Questionnaire (ACQ-5) Score Increase From Baseline | 39 | 30 |
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.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Percentage of Participants Who Have Pre-bronchodilator FEV1 Decrease From Baseline >7.5 % | 63 | 68 |
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.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Percentage of Participants With Inability to Titrate Inhaled Corticosteroids (ICS) | 23 | 30 |
A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Percentage of Participants With Clinically Significant Asthma Exacerbation | 7 | 13 |
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.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Percentage of Participants With Loss of Asthma Control Over Weeks 0-6 | 50 | 36 |
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.
| Days | Placebo | GSK3772847 |
|---|---|---|
| Time to Loss of Asthma Control | 50 (29 to NA) | 96 (31 to NA) |
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.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Percentage of Participants With Clinically Significant Asthma Exacerbation or Inability to Titrate | 25 | 40 |
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.
| Participants | Placebo | GSK3772847 |
|---|---|---|
| Number of Participants Experiencing Asthma Related Hospitalization During the Study Period | 1 | 0 |
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.
| Events per person-year | Placebo | GSK3772847 |
|---|---|---|
| Rate Per 1000 Person-years of Participants With Hospitalization | 70.5 | 0 |
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.
| Participants | Placebo | GSK3772847 |
|---|---|---|
| 0 | 77 | 78 |
| 1 | 1 | 0 |
| 2 | 0 | 0 |
| >=3 | 0 | 0 |
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.
| Scores on a scale | Placebo | GSK3772847 |
|---|---|---|
| Week1; n=72, 73 | -0.36 ± 0.713 | -0.48 ± 0.685 |
| Week2; n=67, 68 | -0.53 ± 0.666 | -0.74 ± 0.732 |
| Week3; n=61, 61 | -0.59 ± 0.722 | -0.78 ± 0.663 |
| Week4; n=54, 59 | -0.69 ± 0.733 | -0.79 ± 0.695 |
| Week5; n= 42, 52 | -0.80 ± 0.839 | -0.78 ± 0.804 |
| Week6; n=40, 48 | -0.80 ± 0.907 | -0.93 ± 0.692 |
| Week7; n=34, 46 | -0.92 ± 0.710 | -0.93 ± 0.785 |
| Week8; n=33, 44 | -0.95 ± 0.769 | -1.00 ± 0.755 |
| Week9; n=30, 42 | -0.93 ± 0.713 | -0.97 ± 0.817 |
| Week10; n=29, 41 | -0.97 ± 0.820 | -0.99 ± 0.729 |
| Week11; n=22, 38 | -1.05 ± 0.907 | -1.07 ± 0.770 |
| Week12; n=23, 38 | -0.88 ± 1.134 | -1.16 ± 0.795 |
| Week13; n=17,32 | -1.40 ± 0.860 | -1.06 ± 0.773 |
| Week14; n=17, 31 | -1.33 ± 0.943 | -1.14 ± 0.820 |
| Week15; n=17, 27 | -1.22 ± 0.874 | -1.21 ± 0.814 |
| Week16; n=12, 21 | -1.15 ± 1.102 | -1.17 ± 0.738 |
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.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Week1; n=72, 73 | 38 | 41 |
| Week2; n=67, 68 | 46 | 56 |
| Week3; n=61, 61 | 49 | 56 |
| Week4; n=54, 59 | 59 | 61 |
| Week5; n= 42, 52 | 62 | 65 |
| Week6; n=40, 48 | 63 | 69 |
| Week7; n=34, 46 | 74 | 65 |
| Week8; n=33, 44 | 70 | 73 |
| Week9; n=30, 42 | 70 | 71 |
| Week10; n=29, 41 | 69 | 76 |
| Week11; n=22, 38 | 64 | 79 |
| Week12; n=23, 38 | 57 | 79 |
| Week13; n=17,32 | 82 | 75 |
| Week14; n=17, 31 | 71 | 74 |
| Week15; n=17, 27 | 76 | 74 |
| Week16; n=12, 21 | 67 | 81 |
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.
| Scores on a scale | Placebo | GSK3772847 |
|---|---|---|
| Week4; n=43, 52 | -10.0 ± 14.98 | -7.0 ± 11.41 |
| Week8; n=31, 42 | -10.7 ± 15.32 | -7.2 ± 17.08 |
| Week12; n=23, 35 | -15.8 ± 21.42 | -12.9 ± 14.91 |
| Week16; n=16, 26 | -12.4 ± 20.75 | -16.5 ± 18.51 |
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.
| Percentage of participants | Placebo | GSK3772847 |
|---|---|---|
| Week4; n=43, 52 | 60 | 58 |
| Week8; n=31, 42 | 61 | 67 |
| Week12; n=23, 35 | 70 | 74 |
| Week16; n=16, 26 | 69 | 88 |
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.
| Liters | Placebo | GSK3772847 |
|---|---|---|
| Week2; n=64, 66 | 0.094 ± 0.2359 | 0.089 ± 0.2443 |
| Week4; n=48, 56 | 0.074 ± 0.3077 | 0.086 ± 0.2325 |
| Week6; n=38, 50 | 0.078 ± 0.2610 | 0.135 ± 0.3758 |
| Week8; n=33, 45 | 0.049 ± 0.2888 | 0.089 ± 0.2236 |
| Week10; n=33, 43 | 0.047 ± 0.2563 | 0.066 ± 0.2372 |
| Week12; n=23, 36 | 0.061 ± 0.2759 | 0.037 ± 0.2637 |
| Week14; n=21, 36 | 0.079 ± 0.2824 | 0.047 ± 0.3200 |
| Week16; n=15, 26 | 0.063 ± 0.3383 | 0.025 ± 0.3008 |
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
| Liters/minute | Placebo | GSK3772847 |
|---|---|---|
| Morning PEF: Weeks 1-4,n=76, 76 | 4.13 ± 35.492 | 4.32 ± 43.773 |
| Morning PEF: Weeks 5-8,n=50, 56 | -1.84 ± 65.222 | -3.82 ± 46.621 |
| Morning PEF: Weeks 9-12,n=31, 43 | -4.15 ± 46.588 | -1.69 ± 45.192 |
| Morning PEF: Weeks 13-16,n=20, 38 | -7.88 ± 47.190 | -1.83 ± 69.866 |
| Evening PEF: Weeks 1-4,n=76, 77 | 0.43 ± 36.087 | 2.45 ± 37.712 |
| Evening PEF: Weeks 5-8,n=52, 58 | -6.96 ± 61.987 | -4.38 ± 49.076 |
| Evening PEF: Weeks 9-12,n=33, 44 | -0.77 ± 54.768 | -0.58 ± 39.929 |
| Evening PEF: Weeks 13-16,n=21, 38 | -10.81 ± 51.566 | -1.16 ± 63.383 |
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.
| Scores on a scale | Placebo | GSK3772847 |
|---|---|---|
| Weeks 1-4, n=77, 78 | -0.09 ± 0.472 | -0.02 ± 0.337 |
| Weeks 5-8, n=52, 59 | -0.18 ± 0.610 | -0.09 ± 0.460 |
| Weeks 9-12 ,n=33,34 | -0.29 ± 0.631 | -0.08 ± 0.473 |
| Weeks 13-16, n=21, 38 | -0.29 ± 0.692 | -0.17 ± 0.458 |
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.
| Inhalations per day | Placebo | GSK3772847 |
|---|---|---|
| Weeks 1-4, n=78, 75 | -0.52 ± 2.554 | -1.09 ± 4.687 |
| Weeks 5-8, n=56, 57 | -0.52 ± 1.740 | -1.24 ± 5.180 |
| Weeks 9-12, n=32, 42 | -0.17 ± 0.945 | -1.59 ± 5.934 |
| Weeks 13-16, n=24, 37 | 0.01 ± 2.005 | -1.90 ± 6.624 |
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.
| Percentage of nights with awakenings | Placebo | GSK3772847 |
|---|---|---|
| Weeks 1-4, n=77, 76 | -3.80 ± 25.712 | -7.42 ± 23.847 |
| Weeks 5-8,n=50, 56 | -7.85 ± 26.325 | -10.49 ± 31.081 |
| Weeks 9-12,n=31, 43 | -5.67 ± 24.669 | -13.43 ± 26.962 |
| Weeks 13-16,n=20, 38 | -2.31 ± 30.355 | -14.91 ± 33.544 |
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.
| Percent Change | Placebo | GSK3772847 |
|---|---|---|
| Week1; n=60, 63 | -3.6 (-46 to 126) | -4.9 (-57 to 281) |
| Week2; n=58, 59 | 15.4 (-57 to 481) | 0.0 (-66 to 206) |
| Week4; n=41, 50 | 15.2 (-64 to 302) | 3.3 (-69 to 546) |
| Week6; n=34, 46 | 5.0 (-71 to 537) | 0.0 (-62 to 221) |
| Week8; n=29, 38 | 15.9 (-60 to 548) | -2.9 (-40 to 148) |
| Week10; n=29, 37 | 13.8 (-54 to 483) | 0.0 (-52 to 252) |
| Week12; n=19, 31 | 31.4 (-40 to 422) | 8.8 (-47 to 413) |
| Week14; n=19, 30 | 28.1 (-43 to 483) | 1.7 (-48 to 457) |
| Week16; n=13, 22 | 85.9 (-33 to 635) | 12.7 (-51 to 695) |
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.
| Participants | Placebo | GSK3772847 |
|---|---|---|
| non-SAE | 20 | 19 |
| SAE | 1 | 2 |
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.
| Millimeters of Mercury (mmHg) | Placebo | GSK3772847 |
|---|---|---|
| SBP: Post-dose: Week0; n=82, 83 | -2.0 ± 8.05 | 1.3 ± 7.19 |
| SBP: Week1; n=79, 75 | -0.9 ± 9.61 | 0.4 ± 9.67 |
| SBP: Week2; n=73, 75 | -1.3 ± 10.73 | -1.3 ± 10.58 |
| SBP: Pre-dose: Week4; n=49, 59 | -2.0 ± 8.88 | -0.1 ± 8.84 |
| SBP: Post-dose: Week4; n=48, 59 | -2.0 ± 9.46 | 2.2 ± 10.72 |
| SBP:Week6; n=45, 57 | -1.7 ± 9.33 | 0.9 ± 9.38 |
| SBP: Pre-Dose:Week8; n=34, 47 | -1.9 ± 7.85 | 0.4 ± 7.91 |
| SBP: Post-DoseWeek8; n=34, 47 | -2.7 ± 9.81 | 2.3 ± 9.46 |
| SBP: Week10; n=34, 46 | -2.5 ± 10.20 | 0.7 ± 11.74 |
| SBP: Pre-dose: Week12; n=24, 39 | 0.3 ± 8.34 | 1.5 ± 10.19 |
| SBP: Post-dose: Week12; n=24, 39 | -0.7 ± 6.34 | 3.3 ± 11.23 |
| SBP: Week14; n=24, 39 | -1.6 ± 9.17 | 2.1 ± 10.47 |
| SBP: Week16; n=24, 39 | -2.8 ± 9.16 | 1.5 ± 10.37 |
| SBP: Week20; n=76, 78 | -1.0 ± 10.72 | 1.7 ± 10.32 |
| SBP: Week24; n=75, 76 | -2.4 ± 10.78 | 1.7 ± 10.46 |
| SBP: Week28; n=74, 77 | -1.3 ± 9.95 | 1.0 ± 9.77 |
| DBP: Post-dose: Week0; n=82,83 | -0.7 ± 6.58 | -0.3 ± 5.67 |
| DBP: Week1; n=79, 75 | 0.3 ± 6.96 | 0.7 ± 8.29 |
| DBP: Week2; n=73, 75 | -0.7 ± 8.61 | -0.8 ± 7.04 |
| DBP: Pre-dose: Week4; n=49, 59 | -1.1 ± 8.26 | 0.4 ± 7.72 |
| DBP: Post-dose: Week4; n=48, 59 | -0.4 ± 7.93 | 0.3 ± 7.79 |
| DBP:Week6; n=45, 57 | 0.6 ± 7.72 | -1.0 ± 7.32 |
| DBP: Pre-Dose:Week8; n=34, 47 | -0.4 ± 7.66 | -2.0 ± 7.79 |
| DBP: Post-DoseWeek8; n=34, 47 | -0.1 ± 7.54 | -1.2 ± 7.21 |
| DBP: Week10; n=34, 46 | -0.1 ± 9.36 | -0.2 ± 7.94 |
| DBP: Pre-dose: Week12; n=24, 39 | 0.3 ± 7.27 | 0.6 ± 6.52 |
| DBP: Post-dose: Week12; n=24, 39 | 0.0 ± 8.08 | -0.5 ± 6.79 |
| DBP: Week14; n=24, 39 | 0.0 ± 5.28 | 0.5 ± 6.84 |
| DBP: Week16; n=24, 39 | -0.3 ± 8.37 | -0.5 ± 5.59 |
| DBP: Week20; n=76, 78 | -0.4 ± 8.61 | 0.7 ± 6.60 |
| DBP: Week24; n=75, 76 | 0.1 ± 8.15 | 0.3 ± 7.06 |
| DBP: Week28; n=74, 77 | -0.3 ± 9.74 | -0.4 ± 7.62 |
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.
| Beats per minute | Placebo | GSK3772847 |
|---|---|---|
| Post-dose: Week0; n=82, 83 | -2.2 ± 7.20 | -0.1 ± 6.54 |
| Week1; n=79, 75 | 0.8 ± 6.12 | 3.1 ± 7.95 |
| Week2; n=73, 75 | 2.9 ± 7.31 | 1.7 ± 7.86 |
| Pre-dose:Week4; n=49, 59 | -0.3 ± 9.73 | 0.1 ± 9.72 |
| Post-dose:Week4; n=48, 59 | -2.0 ± 10.00 | -1.0 ± 10.93 |
| Week6; n=45, 57 | 3.3 ± 11.85 | 2.8 ± 9.26 |
| Pre-dose: Week8; n=34, 47 | -0.3 ± 9.11 | 1.0 ± 7.62 |
| Post-dose: Week8; n=34, 47 | -0.9 ± 10.39 | -0.6 ± 9.71 |
| Week10; n=34, 46 | 2.6 ± 8.86 | 2.4 ± 6.72 |
| Pre-dose: Week12; n=24, 39 | 2.8 ± 8.04 | 1.7 ± 7.53 |
| Post-dose: Week12; n=24, 39 | 0.9 ± 8.84 | -1.2 ± 10.57 |
| Week14; n=24, 39 | 3.1 ± 9.81 | 3.6 ± 6.62 |
| Week16; n=24, 39 | 3.5 ± 9.14 | 2.6 ± 8.30 |
| Week20; n=76, 78 | 2.1 ± 8.34 | 3.6 ± 9.48 |
| Week24; n=75, 76 | 2.3 ± 8.00 | 2.5 ± 7.98 |
| Week28; n=74, 77 | 2.5 ± 8.50 | 2.3 ± 7.98 |
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.
| mmHg | Placebo | GSK3772847 |
|---|---|---|
| SBP: Week0; n=82, 83 | -2.0 ± 8.05 | 1.3 ± 7.19 |
| SBP: Week4; n=48, 59 | -0.4 ± 5.70 | 2.4 ± 9.32 |
| SBP: Week8; n=34, 47 | -0.8 ± 6.03 | 1.9 ± 6.58 |
| SBP: Week12; n=24, 39 | -0.9 ± 7.51 | 1.8 ± 8.72 |
| DBP: Week0; n=82, 83 | -0.7 ± 6.58 | -0.3 ± 5.67 |
| DBP: Week4; n=48, 59 | 0.4 ± 4.95 | -0.1 ± 6.76 |
| DBP: Week8; n=34, 47 | 0.2 ± 4.38 | 0.8 ± 5.55 |
| DBP: Week12; n=24, 39 | -0.3 ± 4.70 | -1.1 ± 6.08 |
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.
| Beats per minute | Placebo | GSK3772847 |
|---|---|---|
| Week0; n=82, 83 | -2.2 ± 7.20 | -0.1 ± 6.54 |
| Week4; n=48, 59 | -1.6 ± 5.75 | -1.1 ± 6.85 |
| Week8; n=34, 47 | -0.5 ± 7.21 | -1.6 ± 6.02 |
| Week12; n=24, 39 | -2.0 ± 5.97 | -2.9 ± 9.05 |
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.
| milliseconds | Placebo | GSK3772847 |
|---|---|---|
| PR: Post-dose: Week0; n=80, 80 | 1.8 ± 9.77 | 3.1 ± 9.28 |
| PR: Pre-dose: Week4; n=49, 59 | -0.4 ± 7.91 | 1.3 ± 10.93 |
| PR: Post-dose: Week4; n=48, 59 | 1.2 ± 9.74 | 1.9 ± 11.76 |
| PR: Pre-dose: Week8; n=34, 47 | 0.0 ± 8.69 | 1.4 ± 11.70 |
| PR:Post-dose: Week8; n=33, 47 | 0.5 ± 11.47 | 1.5 ± 11.30 |
| PR: Pre-dose:Week12; n=24, 39 | -1.3 ± 9.51 | -0.5 ± 13.17 |
| PR: Post-dose Week12; n=24, 39 | 1.3 ± 10.85 | 2.2 ± 12.59 |
| PR: Week16; n=24, 39 | -0.6 ± 10.22 | -0.7 ± 12.91 |
| QRS:Post-dose Week0; n=80, 80 | 0.0 ± 5.75 | 0.2 ± 5.60 |
| QRS:Pre-dose Week4; n=49, 59 | -0.5 ± 5.69 | 0.7 ± 5.72 |
| QRS: Post-dose:Week4; n=48, 59 | -0.2 ± 6.10 | 0.1 ± 6.14 |
| QRS:Pre-dose:Week8; n=34, 47 | 0.2 ± 5.86 | -0.1 ± 4.90 |
| QRS:Post-dose:Week8; n=33, 47 | 0.5 ± 7.02 | 0.1 ± 4.87 |
| QRS:Pre-dose: Week12; n=24, 39 | -1.3 ± 4.83 | -1.1 ± 7.13 |
| QRS:Post-dose: Week12; n=24, 39 | -0.7 ± 6.03 | -1.8 ± 6.21 |
| QRS:Week16; n=24, 39 | -1.6 ± 6.19 | -2.0 ± 6.25 |
| QT:Post-dose: Week0; n=80, 80 | 7.4 ± 19.67 | 3.5 ± 16.69 |
| QT:Pre-dose: Week4; n=49, 59 | -1.7 ± 21.48 | -1.8 ± 17.93 |
| QT:Post-dose: Week4; n=48, 59 | 8.9 ± 23.09 | 5.1 ± 18.78 |
| QT:Pre-dose: Week8; n=34, 47 | 3.5 ± 23.67 | -4.7 ± 20.53 |
| QT:Pre-dose: Week8; n=33, 47 | 6.7 ± 30.69 | 7.0 ± 23.49 |
| QT Pre-dose:Week12; n=24, 39 | 1.5 ± 22.31 | -3.1 ± 23.54 |
| QT:Post-dose:Week12; n=24, 39 | 3.3 ± 24.38 | 2.4 ± 23.16 |
| QT:Week16; n=24,39 | -2.2 ± 21.15 | -7.3 ± 20.68 |
| QTcF:Post-dose:Week0; n=80, 80 | 4.2 ± 12.56 | 3.8 ± 11.21 |
| QTcF:Pre-dose:Week4; n=49, 59 | -1.4 ± 11.35 | -1.0 ± 12.10 |
| QTcF:Post-dose:Week4; n=48, 59 | 4.0 ± 13.57 | 2.0 ± 12.46 |
| QTcF:Pre-dose:Week8; n=34, 47 | 6.4 ± 13.00 | -0.9 ± 14.54 |
| QTcF:Post-dose:Week8; n=33, 47 | 5.5 ± 12.86 | 5.8 ± 16.08 |
| QTcF:Pre-dose:Week12; n=24, 39 | 3.3 ± 13.45 | 0.4 ± 17.56 |
| QTcF:Post-dose: Week12; n=24, 39 | 4.4 ± 13.91 | 2.9 ± 14.33 |
| QTcF: Week16; n=24, 39 | -0.5 ± 11.87 | -2.2 ± 14.83 |
| RR:Post-dose: Week0; n=80, 80 | 24.0 ± 104.42 | -0.2 ± 89.38 |
| RR:Pre-dose: Week4; n=49, 59 | -1.3 ± 114.81 | -2.0 ± 96.20 |
| RR:Post-dose: Week4; n=48, 59 | 36.2 ± 118.51 | 26.7 ± 110.84 |
| RR:Pre-dose:Week8; n=34, 47 | -17.4 ± 135.17 | -24.2 ± 92.65 |
| RR:Post-dose:Week8; n=33, 47 | 10.8 ± 176.36 | 10.7 ± 97.02 |
| RR:Pre-dose:Week12; n=24, 39 | -12.6 ± 107.36 | -21.6 ± 100.97 |
| RR:Post-dose:Week12; n=24, 39 | -4.8 ± 148.89 | 1.3 ± 118.83 |
| RR:Week16; n=24, 39 | -14.4 ± 113.07 | -33.9 ± 102.02 |
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.
| Beats per minute | Placebo | GSK3772847 |
|---|---|---|
| Post-dose: Week0; n=82, 83 | -1.6 ± 7.57 | 0.2 ± 6.93 |
| Pre-dose: Week4; n=49, 59 | 0.4 ± 9.06 | 0.7 ± 7.94 |
| Post-dose: Week4; n=48, 59 | -2.4 ± 9.09 | -1.0 ± 8.48 |
| Pre-dose: Week8; n=34, 47 | 1.5 ± 11.81 | 1.9 ± 6.98 |
| Post-dose: Week8; n=33, 47 | -0.3 ± 15.59 | -0.4 ± 7.57 |
| Pre-dose:Week12; n=24, 39 | 0.6 ± 8.98 | 1.6 ± 7.56 |
| Post-dose Week12; n=24, 39 | 0.4 ± 12.44 | 0.5 ± 9.28 |
| Week16; n=24, 39 | 0.5 ± 10.04 | 3.1 ± 8.12 |
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.
| Degrees | Placebo | GSK3772847 |
|---|---|---|
| Post-dose: Week0; n=80, 80 | -0.8 ± 10.76 | 1.9 ± 6.75 |
| Pre-dose: Week4; n=49, 59 | 0.7 ± 14.30 | 2.3 ± 13.77 |
| Post-dose: Week4; n=48, 59 | -0.1 ± 16.72 | 1.4 ± 11.95 |
| Pre-dose: Week8; n=34, 47 | -0.2 ± 10.56 | -1.0 ± 9.34 |
| Post-dose: Week8; n=33, 47 | 1.0 ± 9.88 | -1.2 ± 8.37 |
| Pre-dose:Week12; n=24, 39 | 0.2 ± 8.59 | 2.0 ± 31.39 |
| Post-dose Week12; n=24, 39 | -1.3 ± 9.49 | -1.2 ± 15.73 |
| Week16; n=24, 39 | 2.3 ± 11.35 | -1.4 ± 10.88 |
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.
| milliseconds | Placebo | GSK3772847 |
|---|---|---|
| PR:Week0; n=80, 80 | 1.8 ± 9.77 | 3.1 ± 9.28 |
| PR: Week4; n=48, 59 | 1.7 ± 8.04 | 0.5 ± 9.77 |
| PR: Week8; n=33, 47 | 0.3 ± 8.70 | -0.1 ± 9.96 |
| PR: Week12; n=24, 39 | 2.2 ± 10.00 | 3.0 ± 9.86 |
| QRS:Week0; n=80, 80 | 0.0 ± 5.75 | 0.2 ± 5.60 |
| QRS: Week4; n=48, 59 | 0.1 ± 4.35 | -0.8 ± 5.58 |
| QRS:Week8; n=33, 47 | 0.3 ± 7.03 | 0.4 ± 4.86 |
| QRS:Week12; n=24, 39 | 0.7 ± 5.36 | -0.9 ± 4.60 |
| QT:Week0; n=80, 80 | 7.4 ± 19.67 | 3.5 ± 16.69 |
| QT:Week4; n=48, 59 | 10.8 ± 13.32 | 6.9 ± 15.63 |
| QT:Week8; n=33, 47 | 3.4 ± 19.22 | 11.5 ± 17.57 |
| QT:Week12; n=24, 39 | 1.9 ± 17.17 | 4.6 ± 18.77 |
| QTcFWeek0; n=80, 80 | 4.2 ± 12.56 | 3.8 ± 11.21 |
| QTcF:Week4; n=48, 59 | 5.4 ± 9.51 | 2.9 ± 10.88 |
| QTcF:Week8; n=33, 47 | -0.7 ± 10.17 | 6.6 ± 10.65 |
| QTcF:Week12; n=24, 39 | 1.1 ± 13.28 | 2.0 ± 13.48 |
| RR:Week0; n=80, 80 | 24.0 ± 104.42 | -0.2 ± 89.38 |
| RR:Week4; n=48, 59 | 37.6 ± 83.83 | 29.5 ± 88.38 |
| RR:Week8; n=33, 47 | 29.3 ± 97.67 | 34.4 ± 95.05 |
| RR:Week12; n=24, 39 | 8.8 ± 83.16 | 20.7 ± 104.02 |
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.
| Beats per minute | Placebo | GSK3772847 |
|---|---|---|
| Week0; n=80, 80 | -1.6 ± 7.57 | 0.2 ± 6.93 |
| Week4; n=48, 59 | -2.9 ± 5.79 | -1.7 ± 6.15 |
| Week8; n=33, 47 | -1.8 ± 8.74 | -2.3 ± 6.83 |
| Week12; n=24, 39 | -0.2 ± 6.69 | -0.9 ± 7.75 |
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.
| Degrees | Placebo | GSK3772847 |
|---|---|---|
| Week0; n=80, 80 | -0.8 ± 10.76 | 1.9 ± 6.75 |
| Week4; n=48, 59 | -0.3 ± 9.20 | -0.9 ± 16.22 |
| Week8; n=33, 47 | 1.2 ± 10.01 | -0.2 ± 9.30 |
| Week12; n=24, 39 | -1.6 ± 6.44 | 2.8 ± 14.25 |
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.
| Beats per minute | Placebo | GSK3772847 |
|---|---|---|
| Mean Heart Rate: Week0; n=81, 80 | -1.1 ± 6.56 | -2.0 ± 6.00 |
| Mean Heart Rate: Week4; n=49, 58 | 76.8 ± 10.60 | 80.0 ± 10.80 |
| Mean Heart Rate: Week12; n=24, 37 | 78.8 ± 11.12 | 79.9 ± 10.08 |
| Maximum Heart Rate: Week0; n=81, 80 | -0.3 ± 13.13 | -5.0 ± 14.55 |
| Maximum Heart Rate: Week4; n=49, 58 | 128.3 ± 13.03 | 130.3 ± 16.41 |
| Maximum Heart Rate: Week12; n=24, 37 | 128.5 ± 15.21 | 132.1 ± 15.80 |
| Minimum Heart Rate: Week0; n=81, 80 | -0.8 ± 5.08 | -0.8 ± 4.55 |
| Minimum Heart Rate: Week4; n=49, 58 | 50.6 ± 7.49 | 53.8 ± 8.15 |
| Minimum Heart Rate: Week12; n=24, 37 | 53.6 ± 7.49 | 53.4 ± 9.09 |
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.
| Events per hour | Placebo | GSK3772847 |
|---|---|---|
| supraventricular couplets: Week0; n=81, 80 | -2.0 ± 21.68 | 16.5 ± 144.04 |
| supraventricular couplets: Week4; n=49, 58 | -1.9 ± 14.11 | -2.2 ± 9.86 |
| supraventricular couplets: Week12; n=24, 37 | -3.9 ± 35.82 | -0.5 ± 3.48 |
| supraventricular ectopics: Week0; n=81, 80 | 2.6 ± 369.71 | 6.8 ± 188.46 |
| supraventricular ectopics: Week4; n=49, 58 | -30.9 ± 445.93 | -7.3 ± 148.20 |
| supraventricular ectopics: Week12; n=24, 37 | 34.9 ± 300.07 | 9.4 ± 94.82 |
| supraventricular runs: Week0; n=81, 80 | -0.5 ± 3.62 | 0.2 ± 2.09 |
| supraventricular runs: Week4; n=49, 58 | -0.1 ± 2.37 | -0.6 ± 3.01 |
| supraventricular runs: Week12; n=24, 37 | -1.1 ± 6.30 | -0.4 ± 1.83 |
| supraventricular singles: Week0; n=81, 80 | 9.0 ± 349.81 | -13.1 ± 120.73 |
| supraventricular singles: Week4; n=49, 58 | -25.3 ± 425.20 | -3.1 ± 138.30 |
| supraventricular singles: Week12; n=24, 37 | 45.5 ± 263.03 | 8.4 ± 89.64 |
| ventricular couplets: Week0; n=81, 80 | 0.7 ± 3.80 | -0.1 ± 1.59 |
| ventricular couplets: Week4; n=49, 58 | 0.2 ± 0.80 | 0.1 ± 0.65 |
| ventricular couplets: Week12; n=24, 37 | 0.0 ± 0.00 | 0.3 ± 1.43 |
| ventricular ectopics: Week0; n=81, 80 | 44.6 ± 265.28 | -12.2 ± 141.39 |
| ventricular ectopics: Week4; n=49, 58 | -10.7 ± 105.24 | 6.4 ± 54.80 |
| ventricular ectopics: Week12; n=24, 37 | -5.3 ± 52.78 | 176.0 ± 926.75 |
| ventricular runs: Week0; n=81, 80 | 0.0 ± 0.25 | 0.0 ± 0.19 |
| ventricular runs: Week4; n=49, 58 | 0.0 ± 0.29 | 0.0 ± 0.00 |
| ventricular runs: Week12; n=24, 37 | 0.0 ± 0.29 | 0.0 ± 0.00 |
| ventricular singles: Week0; n=81, 80 | 44.0 ± 228.09 | -12.2 ± 139.28 |
| ventricular singles: Week4; n=49, 58 | -10.4 ± 104.12 | 6.3 ± 53.79 |
| ventricular singles: Week12; n=24, 37 | -5.4 ± 53.23 | 174.5 ± 921.42 |
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.
| International units per liter | Placebo | GSK3772847 |
|---|---|---|
| ALT: Week 2; n=72, 74 | -0.9 ± 8.88 | -0.2 ± 7.07 |
| ALT:Week 4; n=47,59 | -0.5 ± 9.50 | -2.6 ± 7.24 |
| ALT: Week 8; n=34,47 | -0.1 ± 6.93 | -2.4 ± 7.30 |
| ALT: Week 12; n=24, 36 | -1.6 ± 6.86 | -2.4 ± 7.77 |
| ALT: Week 16; n=24, 39 | -1.2 ± 7.97 | -2.6 ± 6.54 |
| ALT: Week 28; n=74, 74 | -1.1 ± 9.57 | -0.9 ± 10.51 |
| ALP: Week 2; n=72, 74 | -1.9 ± 8.32 | -0.8 ± 8.96 |
| ALP:Week 4; n=47, 59 | -0.8 ± 13.18 | -1.0 ± 8.17 |
| ALP:Week 8; n=34, 47 | 0.9 ± 7.37 | -2.3 ± 8.64 |
| ALP:Week 12; n =24, 36 | 2.4 ± 8.79 | -3.0 ± 14.01 |
| ALP:Week 16; n=24, 39 | 1.0 ± 9.33 | -2.3 ± 9.75 |
| ALP:Week 28; n=74, 74 | -0.4 ± 12.33 | -1.2 ± 13.25 |
| AST: Week 2; n=72, 74 | -0.8 ± 9.30 | -1.5 ± 6.59 |
| AST:Week 4; n=47,59 | -1.0 ± 6.02 | -2.5 ± 6.75 |
| AST:Week 8, n=34,47 | -1.6 ± 6.58 | -2.7 ± 6.36 |
| AST:Week 12, n=24, 36 | -1.8 ± 4.91 | -4.1 ± 6.59 |
| AST:Week 16, n=24, 39 | -1.4 ± 6.01 | -3.3 ± 6.70 |
| AST:Week 28, n=74, 74 | -2.3 ± 6.96 | -1.7 ± 8.64 |
| CK: Week 2, n=72, 74 | -12.5 ± 92.00 | -18.8 ± 207.72 |
| CK:Week 4, n=47,59 | -30.3 ± 68.86 | -45.1 ± 231.07 |
| CK:Week 8, n=34,47 | -26.6 ± 57.01 | -32.9 ± 242.98 |
| CK:Week 12, n=24, 36 | -5.0 ± 73.56 | -54.5 ± 282.17 |
| CK:Week 16, n=24, 39 | -20.8 ± 81.02 | -46.8 ± 272.08 |
| CK:Week 28, n=74, 74 | -8.5 ± 131.56 | -30.7 ± 199.41 |
| GGT: Week 2, n=72, 74 | -3.2 ± 9.61 | -1.2 ± 12.16 |
| GGT:Week 4, n=47,59 | -3.9 ± 14.00 | -2.5 ± 21.35 |
| GGT:Week 8, n=34,47 | -3.5 ± 13.50 | -2.8 ± 15.61 |
| GGT:Week 12, 24, 36 | -0.3 ± 5.87 | -5.4 ± 19.48 |
| GGT:Week 16, n=24, 39 | -1.1 ± 4.41 | -3.9 ± 14.64 |
| GGT:Week 28, n=74, 73 | -3.2 ± 13.80 | -0.7 ± 16.06 |
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.
| Millimoles per liter | Placebo | GSK3772847 |
|---|---|---|
| Glucose: Week 2; n=72, 74 | 0.13 ± 0.996 | 0.05 ± 1.273 |
| Glucose:Week 4; n=47,59 | 0.18 ± 0.784 | 0.19 ± 1.156 |
| Glucose:Week 8; n=34,47 | 0.26 ± 1.008 | 0.00 ± 1.400 |
| Glucose:Week 12; n=24, 36 | -0.04 ± 0.796 | 0.20 ± 1.516 |
| Glucose:Week 16; n=24, 39 | -0.10 ± 1.057 | 0.12 ± 0.984 |
| Glucose:Week 28; n=74, 73 | 0.30 ± 1.245 | 0.04 ± 1.780 |
| Potassium: Week 2; n=72, 74 | 0.14 ± 0.366 | 0.13 ± 0.596 |
| Potassium:Week 4; n=47,59 | 0.04 ± 0.361 | 0.05 ± 0.402 |
| Potassium:Week 8; n=34,47 | -0.01 ± 0.352 | -0.04 ± 0.397 |
| Potassium:Week 12; n=24, 36 | 0.02 ± 0.363 | 0.00 ± 0.439 |
| Potassium:Week 16; n=24, 39 | -0.09 ± 0.403 | 0.00 ± 0.439 |
| Potassium:Week 28; n=74, 73 | 0.01 ± 0.407 | 0.01 ± 0.416 |
| Sodium: Week 2; n=72, 74 | 0.3 ± 2.19 | -0.1 ± 2.31 |
| Sodium:Week 4; n=47,59 | 0.0 ± 1.65 | -0.9 ± 2.34 |
| Sodium:Week 8; n=34,47 | -0.1 ± 1.41 | -0.6 ± 1.51 |
| Sodium:Week 12; n=24, 36 | -0.3 ± 2.17 | -1.1 ± 1.71 |
| Sodium:Week 16; n=24, 39 | -0.2 ± 2.14 | -0.3 ± 2.01 |
| Sodium:Week 28; n=74, 73 | 0.5 ± 2.55 | -0.2 ± 2.11 |
| Calcium: Week 2; n=72, 74 | -0.006 ± 0.0691 | 0.001 ± 0.0925 |
| Calcium:Week 4; n=47,59 | -0.013 ± 0.0873 | -0.005 ± 0.0743 |
| Calcium:Week 8; n=34,47 | -0.005 ± 0.0648 | -0.003 ± 0.0997 |
| Calcium:Week 12; n=24, 36 | 0.018 ± 0.0962 | -0.004 ± 0.0949 |
| Calcium:Week 16; n=24, 39 | 0.014 ± 0.0950 | 0.017 ± 0.0963 |
| Calcium:Week 28; n=74, 73 | 0.001 ± 0.0776 | 0.001 ± 0.0994 |
| Phosphate: Week 2; n=72, 74 | 0.031 ± 0.1467 | -0.023 ± 0.1502 |
| Phosphate:Week 4; n=47,59 | 0.003 ± 0.1312 | -0.011 ± 0.1362 |
| Phosphate:Week 8; n=34,47 | 0.006 ± 0.1678 | -0.049 ± 0.1420 |
| Phosphate:Week 12; n=24, 36 | 0.025 ± 0.1133 | -0.013 ± 0.1495 |
| Phosphate:Week 16; n=24, 39 | -0.006 ± 0.1370 | -0.019 ± 0.1503 |
| Phosphate:Week 28; n=74, 73 | -0.013 ± 0.1854 | -0.018 ± 0.1743 |
| Chloride: Week 2; n=72, 74 | 0.3 ± 2.47 | 0.1 ± 2.22 |
| Chloride:Week 4; n=47,59 | 0.0 ± 2.04 | -0.3 ± 2.18 |
| Chloride:Week 8; n=34,47 | -0.2 ± 1.97 | 0.0 ± 2.03 |
| Chloride:Week 12; n=24, 36 | -0.1 ± 2.61 | -0.3 ± 2.13 |
| Chloride:Week 16; n=24, 39 | -0.4 ± 2.95 | -0.2 ± 2.61 |
| Chloride:Week 28; n=74, 73 | 0.6 ± 2.65 | 0.7 ± 2.24 |
| CO2: Week 2; n=72, 74 | -0.4 ± 2.71 | 0.4 ± 2.10 |
| CO2:Week 4; n=47,59 | -0.4 ± 2.26 | 0.3 ± 2.82 |
| CO2:Week 8; n=34,46 | -0.3 ± 1.95 | -0.3 ± 1.84 |
| CO2:Week 12; n=24, 36 | -0.5 ± 2.60 | -0.1 ± 2.10 |
| CO2:Week 16; n=24, 39 | -0.5 ± 2.34 | 0.1 ± 2.28 |
| CO2:Week 28; n=74, 73 | -0.1 ± 2.28 | 0.3 ± 2.15 |
| Urea: Week 2; n=72, 74 | 0.08 ± 1.311 | -0.14 ± 1.108 |
| Urea:Week 4; n=47,59 | 0.16 ± 1.344 | -0.14 ± 1.102 |
| Urea:Week 8; n=34,47 | -0.04 ± 1.264 | 0.27 ± 1.151 |
| Urea:Week 12; n=24, 36 | 0.58 ± 1.537 | -0.06 ± 1.346 |
| Urea:Week 16; n=24, 39 | 0.48 ± 1.379 | 0.03 ± 1.287 |
| Urea:Week 28; n=74, 73 | 0.08 ± 1.089 | 0.16 ± 1.121 |
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.
| Micromoles per liter | Placebo | GSK3772847 |
|---|---|---|
| Creatinine: Week 2; n=72, 74 | 2.35 ± 6.911 | 1.71 ± 8.321 |
| Creatinine:Week 4; n=47, 59 | 2.35 ± 8.319 | 0.72 ± 6.610 |
| Creatinine:Week 8; n=34, 47 | 1.18 ± 7.677 | 1.76 ± 6.072 |
| Creatinine:Week 12; n=24, 36 | 2.42 ± 6.521 | 0.02 ± 5.866 |
| Creatinine:Week 16; n=24, 39 | 2.50 ± 8.685 | 0.91 ± 6.105 |
| Creatinine:Week 28; n=74, 73 | 4.32 ± 6.810 | 2.9 ± 6.356 |
| Total Bilirubin : Week 2; n=72, 74 | -0.1 ± 3.22 | 0.1 ± 2.83 |
| Total Bilirubin :Week 4; n=47, 59 | -0.3 ± 3.24 | -0.4 ± 2.98 |
| Total Bilirubin :Week 8; n=34, 47 | -0.1 ± 2.46 | -0.2 ± 4.04 |
| Total Bilirubin :Week 12; n=24, 36 | -0.6 ± 2.32 | 0.1 ± 4.56 |
| Total Bilirubin :Week 16; n=24, 39 | 0.0 ± 2.83 | -0.3 ± 3.39 |
| Total Bilirubin :Week 28; n=74, 74 | 0.1 ± 2.77 | -0.5 ± 3.94 |
| Direct bilirubin : Week 2; n=72, 74 | -0.1 ± 1.18 | 0.0 ± 1.02 |
| Direct bilirubin :Week 4; n=47,59 | -0.1 ± 0.97 | 0.1 ± 1.11 |
| Direct bilirubin :Week 8; n=34, 47 | -0.1 ± 1.04 | 0.2 ± 1.17 |
| Direct bilirubin :Week 12; n=24, 36 | -0.4 ± 1.18 | 0.2 ± 1.11 |
| Direct bilirubin :Week 16; n=24, 39 | 0.1 ± 1.50 | 0.1 ± 1.07 |
| Direct bilirubin :Week 28; n=74, 74 | 0.1 ± 1.17 | 0.1 ± 1.13 |
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.
| Grams per liter | Placebo | GSK3772847 |
|---|---|---|
| Total Protein: Week 2, n=72, 74 | -0.5 ± 3.49 | 0.4 ± 3.71 |
| Total Protein:Week 4, n=47,59 | -0.4 ± 3.44 | -0.4 ± 3.76 |
| Total Protein:Week 8, n=34,47 | 0.1 ± 3.20 | 0.8 ± 3.83 |
| Total Protein:Week 12, n=24, 36 | 0.2 ± 4.05 | -0.6 ± 4.79 |
| Total Protein:Week 16, n=24, 39 | 0.5 ± 4.33 | 0.4 ± 3.34 |
| Total Protein:Week 28, n=74, 73 | -0.8 ± 4.04 | -0.2 ± 4.27 |
| Albumin: Week 2, n=72, 74 | -0.5 ± 2.38 | -0.4 ± 2.11 |
| Albumin:Week 4, n=47,59 | -0.5 ± 2.29 | -0.8 ± 2.62 |
| Albumin:Week 8, n=34,47 | -0.4 ± 2.36 | 0.0 ± 2.38 |
| Albumin:Week 12, n=24, 36 | -0.3 ± 2.40 | -0.9 ± 2.69 |
| Albumin:Week 16, n=24, 39 | -0.1 ± 2.82 | -0.4 ± 2.25 |
| Albumin:Week 28, n=74, 73 | -0.6 ± 2.70 | -0.6 ± 2.99 |
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.
| 10^9 cells per liter | Placebo | GSK3772847 |
|---|---|---|
| Basophil: Week 1; n=77, 74 | 0.001 ± 0.0361 | -0.001 ± 0.0396 |
| Basophil:Week 2; n= 68, 72 | 0.003 ± 0.0350 | 0.005 ± 0.0346 |
| Basophil:Week 4; n=48, 57 | 0.005 ± 0.0341 | 0.004 ± 0.0409 |
| Basophil:Week 6; n=43, 54 | 0.006 ± 0.0420 | 0.007 ± 0.0363 |
| Basophil:Week 8; n=33, 46 | 0.002 ± 0.0449 | -0.001 ± 0.0366 |
| Basophil:Week 10; n= 32, 44 | 0.004 ± 0.0345 | 0.010 ± 0.0367 |
| Basophil:Week 12; n=24, 39 | 0.010 ± 0.0262 | 0.010 ± 0.0312 |
| Basophil:Week 14; n=23, 39 | -0.003 ± 0.0255 | 0.012 ± 0.0338 |
| Basophil:Week 16; n=23, 39 | -0.005 ± 0.0316 | 0.006 ± 0.0409 |
| Basophil:Week 28; n= 65, 60 | 0.006 ± 0.0364 | 0.007 ± 0.0353 |
| Eosinophil: Week 1; n=77, 74 | -0.031 ± 0.2868 | -0.038 ± 0.1424 |
| Eosinophil:Week 2; n=68, 72 | -0.050 ± 0.2105 | -0.051 ± 0.1892 |
| Eosinophil:Week 4; n=48, 57 | -0.048 ± 0.2585 | -0.119 ± 0.1522 |
| Eosinophil:Week 6; n =43, 54 | -0.023 ± 0.2714 | -0.119 ± 0.1950 |
| Eosinophil:Week 8; n= 33, 46 | -0.014 ± 0.2069 | -0.096 ± 0.2134 |
| Eosinophil:Week 10 n=32, 44 | 0.000 ± 0.2387 | -0.041 ± 0.2371 |
| Eosinophil:Week 12; n=24, 39 | -0.039 ± 0.2621 | -0.066 ± 0.1939 |
| Eosinophil:Week 14; n=23, 39 | 0.018 ± 0.1888 | -0.034 ± 0.2481 |
| Eosinophil:Week 16; n=23, 39 | -0.018 ± 0.2456 | -0.093 ± 0.2350 |
| Eosinophil:Week 28; n= 65, 60 | 0.010 ± 0.2077 | -0.087 ± 0.1865 |
| Leukocytes: Week 1; n=78, 74 | 0.14 ± 1.614 | 0.07 ± 1.314 |
| Leukocytes:Week 2; n= 68, 73 | 0.01 ± 1.202 | 0.09 ± 1.117 |
| Leukocytes:Week 4; n =48, 57 | 0.24 ± 1.406 | 0.19 ± 1.401 |
| Leukocytes:Week 6; n=43, 54 | 0.37 ± 1.346 | -0.12 ± 1.040 |
| Leukocytes:Week 8; n=33, 47 | 0.08 ± 1.045 | 0.14 ± 2.248 |
| Leukocytes:Week 10; n=33, 45 | 0.01 ± 1.102 | 0.03 ± 1.259 |
| Leukocytes:Week 12; n=24, 39 | 0.13 ± 1.257 | 0.18 ± 1.038 |
| Leukocytes:Week 14; n= 23, 39 | -0.17 ± 1.324 | 0.26 ± 1.220 |
| Leukocytes:Week 16; n=23, 39 | -0.41 ± 1.296 | 0.18 ± 1.511 |
| Leukocytes:Week 28; n=65, 63 | -0.08 ± 1.545 | 0.09 ± 1.392 |
| Lymphocytes: Week 1; n=77, 74 | 0.036 ± 0.4248 | -0.008 ± 0.3292 |
| Lymphocytes:Week 2; n=68, 72 | 0.006 ± 0.3437 | 0.039 ± 0.4112 |
| Lymphocytes:Week 4; n=48, 57 | 0.043 ± 0.4048 | 0.061 ± 0.2995 |
| Lymphocytes:Week 6; n=43, 54 | 0.140 ± 0.4994 | 0.086 ± 0.3986 |
| Lymphocytes:Week 8; n=33, 46 | 0.132 ± 0.3257 | 0.033 ± 0.3477 |
| Lymphocytes:Week 10; n=32, 44 | 0.103 ± 0.4275 | 0.105 ± 0.4105 |
| Lymphocytes:Week 12; n=24, 39 | 0.098 ± 0.3657 | 0.044 ± 0.3546 |
| Lymphocytes:Week 14; n=23, 39 | 0.009 ± 0.3590 | 0.119 ± 0.4346 |
| Lymphocytes:Week 16; n=23, 39 | 0.02 ± 0.3825 | 0.075 ± 0.4397 |
| Lymphocytes:Week 28; n=65, 60 | 0.065 ± 0.4601 | 0.162 ± 0.4794 |
| Neutrophils: Week 1; n=77, 74 | 0.079 ± 1.4665 | 0.092 ± 1.1019 |
| Neutrophils:Week 2; n=68, 72 | 0.023 ± 1.0414 | 0.035 ± 0.8299 |
| Neutrophils:Week 4; n=48, 57 | 0.187 ± 1.2738 | 0.217 ± 1.2788 |
| Neutrophils:Week 6; n=43, 54 | 0.203 ± 1.3952 | -0.126 ± 0.8524 |
| Neutrophils:Week 8; n=33, 46 | -0.080 ± 0.9654 | 0.331 ± 2.0776 |
| Neutrophils:Week 10; n=32, 44 | -0.192 ± 0.9739 | 0.041 ± 0.9173 |
| Neutrophils:Week 12; n=24, 39 | -0.013 ± 1.2306 | 0.158 ± 0.8630 |
| Neutrophils:Week 14; n=23, 39 | -0.263 ± 1.3117 | 0.073 ± 0.9305 |
| Neutrophils:Week 16; n=23, 39 | -0.448 ± 1.1201 | 0.142 ± 1.2595 |
| Neutrophils:Week 28; n=65, 60 | -0.201 ± 1.5148 | -0.045 ± 1.1145 |
| Monocytes: Week 1; n=77, 74 | 0.026 ± 0.1595 | 0.015 ± 0.1209 |
| Monocytes:Week 2; n=68, 72 | 0.020 ± 0.1226 | 0.022 ± 0.0965 |
| Monocytes:Week 4; n=48, 57 | 0.051 ± 0.1869 | 0.027 ± 0.1014 |
| Monocytes:Week 6; n=43, 54 | 0.050 ± 0.1353 | 0.038 ± 0.1083 |
| Monocytes:Week 8; n=33, 46 | 0.045 ± 0.1152 | 0.023 ± 0.1038 |
| Monocytes:Week 10; n=32, 44 | 0.090 ± 0.1463 | 0.038 ± 0.100 |
| Monocytes:Week 12; n=24, 39 | 0.073 ± 0.1362 | 0.025 ± 0.0948 |
| Monocytes:Week 14; n=23, 39 | 0.059 ± 0.1301 | 0.082 ± 0.103 |
| Monocytes:Week 16; n=23, 39 | 0.040 ± 0.1087 | 0.053 ± 0.1075 |
| Monocytes:Week 28; n=65, 60 | 0.041 ± 0.1431 | 0.066 ± 0.1218 |
| Platelets: Week 1; n=78, 74 | 1.5 ± 31.89 | 8.7 ± 44.52 |
| Platelets:Week 2; n=71, 74 | 7.6 ± 35.72 | 9.8 ± 44.42 |
| Platelets:Week 4; n=49, 57 | 4.0 ± 27.64 | 5.3 ± 33.05 |
| Platelets:Week 6; n=44, 56 | 18.2 ± 46.02 | 3.9 ± 35.62 |
| Platelets:Week 8; n=34, 47 | 8.6 ± 38.79 | -1.1 ± 30.31 |
| Platelets:Week 10; n=34, 45 | 10.9 ± 45.93 | 4.7 ± 30.88 |
| Platelets:Week 12; n=24, 39 | 3.6 ± 46.24 | 6.6 ± 27.79 |
| Platelets:Week 14; n=24, 39 | -6.4 ± 45.37 | 5.5 ± 32.66 |
| Platelets:Week 16; n=24, 38 | -0.5 ± 37.57 | 6.3 ± 40.13 |
| Platelets:Week 28; n=64, 62 | -3.5 ± 35.52 | 3.0 ± 52.16 |
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.
| Femtoliters | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | 0.3 ± 1.59 | -0.1 ± 1.46 |
| Week 2: n=71, 74 | 0.2 ± 1.44 | -0.2 ± 1.62 |
| Week 4: n=49, 57 | -0.4 ± 1.62 | -0.6 ± 1.98 |
| Week 6: n=44, 56 | -0.3 ± 1.29 | -0.4 ± 2.33 |
| Week 8: n=34, 47 | -0.9 ± 1.37 | -0.6 ± 2.13 |
| Week 10: n=34, 45 | -1.1 ± 1.82 | -0.9 ± 2.52 |
| Week 12: n=24, 39 | -0.7 ± 1.46 | -1.3 ± 2.61 |
| Week 14: n=24, 39 | -0.7 ± 1.63 | -1.5 ± 2.46 |
| Week 16: n=24, 39 | -0.6 ± 1.58 | -2.3 ± 2.67 |
| Week 28: n=65, 63 | -1.6 ± 2.76 | -2.9 ± 5.20 |
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.
| 10^12 cells per liter | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | -0.01 ± 0.220 | -0.03 ± 0.232 |
| Week 2: n=71, 74 | 0.01 ± 0.232 | 0.01 ± 0.200 |
| Week 4: n=49, 57 | 0.05 ± 0.298 | -0.01 ± 0.169 |
| Week 6: n=44, 56 | 0.05 ± 0.181 | -0.04 ± 0.170 |
| Week 8: n=34, 47 | 0.02 ± 0.210 | 0.02 ± 0.234 |
| Week 10: n=34, 45 | 0.00 ± 0.228 | -0.02 ± 0.201 |
| Week 12: n=24, 39 | 0.06 ± 0.226 | -0.03 ± 0.297 |
| Week 14: n=24, 39 | 0.03 ± 0.206 | 0.04 ± 0.253 |
| Week 16: n=24, 39 | 0.00 ± 0.184 | 0.03 ± 0.236 |
| Week 28: n=65, 63 | 0.09 ± 0.260 | 0.09 ± 0.381 |
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.
| Grams per liter | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | 0.5 ± 7.08 | -0.7 ± 6.30 |
| Week 2: n=71, 74 | 0.5 ± 7.01 | 0.0 ± 5.64 |
| Week 4: n=49, 57 | 1.6 ± 8.84 | -0.4 ± 5.16 |
| Week 6: n=44, 56 | 1.5 ± 4.60 | -1.2 ± 5.17 |
| Week 8: n=34, 47 | 0.5 ± 6.16 | -0.1 ± 6.72 |
| Week 10: n=34, 45 | -0.4 ± 5.71 | -0.8 ± 5.28 |
| Week 12: n=24, 39 | 1.0 ± 6.50 | -1.8 ± 10.05 |
| Week 14: n=24, 39 | -0.6 ± 6.08 | -0.3 ± 6.35 |
| Week 16: n=24, 39 | -0.5 ± 5.44 | 0.0 ± 6.14 |
| Week 28: n=65, 63 | 1.0 ± 8.20 | -0.7 ± 10.24 |
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.
| Proportion of red blood cells in blood | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | 0.0007 ± 0.02255 | -0.0025 ± 0.02114 |
| Week 2: n=71, 74 | 0.0024 ± 0.02213 | -0.0046 ± 0.04223 |
| Week 4: n=49, 57 | 0.0038 ± 0.02957 | -0.0033 ± 0.01665 |
| Week 6: n=44, 56 | 0.0024 ± 0.01557 | -0.0050 ± 0.02060 |
| Week 8: n=34, 47 | -0.0019 ± 0.01645 | -0.0015 ± 0.02212 |
| Week 10: n=34, 45 | -0.0050 ± 0.01897 | -0.0061 ± 0.02175 |
| Week 12: n=24, 39 | 0.0009 ± 0.01740 | -0.0088 ± 0.03342 |
| Week 14: n=24, 39 | -0.0018 ± 0.01699 | -0.0038 ± 0.02277 |
| Week 16: n=24, 39 | -0.0042 ± 0.01474 | -0.0071 ± 0.02232 |
| Week 28: n=65, 63 | 0.0016 ± 0.02283 | -0.0041 ± 0.03153 |
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.
| Picogram | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | 0.17 ± 0.725 | 0.01 ± 0.453 |
| Week 2: n=71, 74 | 0.01 ± 0.430 | -0.07 ± 0.471 |
| Week 4: n=49, 57 | 0.01 ± 0.461 | -0.04 ± 0.432 |
| Week 6: n=44, 56 | 0.06 ± 0.416 | 0.00 ± 0.551 |
| Week 8: n=34, 47 | 0.02 ± 0.660 | -0.11 ± 0.567 |
| Week 10: n=34, 45 | -0.06 ± 0.590 | -0.01 ± 0.863 |
| Week 12: n=24, 39 | -0.07 ± 0.543 | -0.12 ± 0.776 |
| Week 14: n=24, 39 | -0.23 ± 0.421 | -0.29 ± 0.785 |
| Week 16: n=24, 39 | -0.05 ± 0.475 | -0.26 ± 0.839 |
| Week 28: n=65, 63 | -0.40 ± 0.649 | -0.78 ± 1.773 |
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.
| Grams per liter | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | 0.8 ± 8.29 | 0.5 ± 6.65 |
| Week 2: n=71, 74 | -0.6 ± 6.04 | 0.2 ± 7.09 |
| Week 4: n=49, 57 | 1.2 ± 7.01 | 1.5 ± 7.32 |
| Week 6: n=44, 56 | 1.9 ± 5.33 | 1.3 ± 9.33 |
| Week 8: n=34, 47 | 3.0 ± 7.65 | 1.1 ± 7.56 |
| Week 10: n=34, 45 | 3.3 ± 6.68 | 3.4 ± 10.17 |
| Week 12: n=24, 39 | 2.3 ± 6.29 | 3.2 ± 10.32 |
| Week 14: n=24, 39 | 0.4 ± 6.47 | 2.4 ± 8.97 |
| Week 16: n=24, 39 | 2.1 ± 7.01 | 5.7 ± 9.60 |
| Week 28: n=65, 63 | 1.2 ± 8.36 | 1.5 ± 8.78 |
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.
| Percentage (%) of Erythrocytes | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | -0.06 ± 0.747 | -0.08 ± 0.604 |
| Week 2: n=71, 74 | -0.02 ± 0.478 | -0.20 ± 0.652 |
| Week 4: n=49, 57 | -0.22 ± 0.555 | -0.33 ± 0.844 |
| Week 6: n=44, 56 | -0.33 ± 0.545 | -0.37 ± 0.861 |
| Week 8: n=34, 47 | -0.40 ± 0.669 | -0.29 ± 0.960 |
| Week 10: n=34, 45 | -0.35 ± 0.791 | -0.38 ± 1.049 |
| Week 12: n=24, 39 | -0.27 ± 0.717 | -0.34 ± 0.916 |
| Week 14: n=24, 39 | -0.28 ± 0.873 | -0.38 ± 0.897 |
| Week 16: n=24, 39 | -0.25 ± 0.727 | -0.41 ± 0.995 |
| Week 28: n=65, 63 | -0.09 ± 1.028 | -0.01 ± 1.202 |
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.
| Nanograms per liter | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=79,75 | -14.8442 ± 61.92992 | 8.4023 ± 54.37938 |
| Week 2: n=73,75 | -10.8134 ± 71.40009 | -2.5196 ± 42.06499 |
| Week 4: n=49, 59 | -17.9849 ± 68.85651 | -4.5560 ± 44.12297 |
| Week 6: n=45, 57 | -5.0620 ± 53.06025 | 3.6194 ± 53.96329 |
| Week 8: n=34, 47 | -8.6398 ± 49.58134 | 9.6509 ± 66.34546 |
| Week 10: n=34, 46 | -12.7377 ± 80.51666 | 14.9119 ± 58.17102 |
| Week 12: n=24, 38 | -13.6951 ± 53.70314 | 8.8531 ± 58.15689 |
| Week 14: n=24, 39 | -4.8082 ± 57.47926 | 20.0149 ± 74.94234 |
| Week 16: n=24, 39 | -19.4899 ± 58.89689 | 4.7760 ± 60.56438 |
| Week 28: n=65, 65 | -6.1970 ± 62.26132 | 0.9810 ± 64.44446 |
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.
| Micrograms per liter | Placebo | GSK3772847 |
|---|---|---|
| Week 1: n=78,74 | 0.000 ± 0.0000 | 0.000 ± 0.0023 |
| Week 2: n=73, 73 | 0.000 ± 0.0016 | 0.000 ± 0.0023 |
| Week 4: n=49, 58 | 0.001 ± 0.0059 | 0.000 ± 0.0000 |
| Week 6: n=45, 57 | 0.000 ± 0.0021 | 0.000 ± 0.0000 |
| Week 8: n=34, 46 | 0.000 ± 0.0017 | 0.000 ± 0.0000 |
| Week 10: n=34, 38 | 0.006 ± 0.0344 | 0.000 ± 0.0000 |
| Week 12: n=24, 39 | 0.000 ± 0.0000 | 0.000 ± 0.0000 |
| Week 14: n=24, 39 | 0.000 ± 0.0000 | 0.000 ± 0.0016 |
| Week 16: n=24, 39 | 0.000 ± 0.0000 | 0.000 ± 0.0000 |
| Week 28: n=63, 63 | 0.000 ± 0.0013 | -0.001 ± 0.0050 |
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
| Participants | Placebo | GSK3772847 |
|---|---|---|
| Week2; n=73, 74 | 0 | 0 |
| Week4; n=49, 59 | 0 | 0 |
| Week8; n=34, 47 | 0 | 0 |
| Week12; n=24, 39 | 0 | 0 |
| Week16; n=23, 39 | 0 | 0 |
| Week20; n=73, 75 | 1 | 0 |
| Week24; n=74, 75 | 0 | 0 |
| Week28; n=74, 74 | 0 | 0 |
Blood samples were collected at given time points to evaluate pharmacokinetics (PK) of GSK3772847 in participants with moderately severe asthma.
| Micrograms per milliliter | GSK3772847 |
|---|---|
| Week2; n=75 | 78.40 ± 30.934 |
| Week4; Pre-dose;n=59 | 44.42 ± 21.774 |
| Week8; Pre-dose; n= 47 | 61.44 ± 30.978 |
| Week12; Pre-dose; n=39 | 63.42 ± 34.420 |
| Week12; Post-dose; n=39 | 224.21 ± 151.780 |
| Week16; n=38 | 63.03 ± 36.328 |
| Week20; n=75 | 25.75 ± 19.074 |
| Week24; n=75 | 12.91 ± 16.061 |
| Week28; n=75 | 6.14 ± 16.005 |
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.
| Percent change | Placebo | GSK3772847 |
|---|---|---|
| Week4; Pre-dose; n=48, 56 | -5.6 (-20.8 to 12.4) | -93.8 (-94.7 to -92.7) |
| Week8; Pre-dose; n=33, 45 | -8.5 (-26.9 to 14.5) | -93.5 (-94.7 to -92.0) |
| Week12; Pre-dose; n=23, 37 | 10.5 (-17.4 to 47.7) | -92.5 (-94.2 to -90.4) |
| Week16; n=16, 26 | 19.8 (-8.8 to 57.3) | -92.0 (-93.7 to -89.9) |
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.
| Percent change | Placebo | GSK3772847 |
|---|---|---|
| Week4; Pre-dose; n=48, 56 | 16.3 (-0.6 to 36.0) | 2691.1 (2314.4 to 3126.6) |
| Week8; Pre-dose; n=33, 45 | -6.9 (-22.7 to 12.0) | 2326.9 (1951.7 to 2770.7) |
| Week12; Pre-dose; n=23, 37 | -13.4 (-33.4 to 12.6) | 1858.0 (1461.4 to 2355.2) |
| Week16; n=16, 26 | -12.0 (-28.5 to 8.3) | 2330.8 (1933.0 to 2806.4) |
Collected over SAEs and non-SAEs were collected for 16 weeks.. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/82 (0%) | 1/82 (1.2%) | 20/82 (24.4%) |
| GSK3772847 | 0/83 (0%) | 2/83 (2.4%) | 19/83 (22.9%) |
| Event | Placebo | GSK3772847 |
|---|---|---|
| PneumoniaInfections and infestations | 1/82 | 0/83 |
| Anaphylactic shockImmune system disorders | 0/82 | 1/83 |
| AngioedemaSkin and subcutaneous tissue disorders | 0/82 | 1/83 |
| Event | Placebo | GSK3772847 |
|---|---|---|
| HeadacheNervous system disorders | 9/82 | 9/83 |
| NasopharyngitisInfections and infestations | 4/82 | 4/83 |
| InfluenzaInfections and infestations | 4/82 | 1/83 |
| Upper respiratory tract infectionInfections and infestations | 1/82 | 4/83 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/82 | 4/83 |
| Ventricular tachycardiaCardiac disorders | 3/82 | 1/83 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/82 | 3/83 |
| Age, Continuous(Years) | Placebo | GSK3772847 | Total |
|---|---|---|---|
| Mean | 54.1 ± 11.65 | 51.8 ± 11.74 | 52.9 ± 11.71 |
| Sex: Female, Male(Participants) | Placebo | GSK3772847 | Total |
|---|---|---|---|
| Female | 54 | 64 | 118 |
| Male | 28 | 19 | 47 |
| Race/Ethnicity, Customized(Participants) | Placebo | GSK3772847 | Total |
|---|---|---|---|
| American Indian or Alaska Native | 14 | 8 | 22 |
| Central/South Asian Heritage | 0 | 1 | 1 |
| Japanese /East Asian/South East Asian Heritage | 1 | 0 | 1 |
| Black or African American | 3 | 8 | 11 |
| White | 64 | 66 | 130 |
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