Trial Outcomes & Findings for Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD) (NCT NCT03393806)
NCT ID: NCT03393806
Last Updated: 2020-10-23
Results Overview
Blood samples were collected at the indicated time points for assessment of blood eosinophil cell count. Baseline is the most recent recorded value before dosing on Day 1. Percent change from Baseline is calculated as (Ratio to Baseline minus 1)\*100, where ratio to Baseline is the value at specified time point divided by Baseline value.
TERMINATED
PHASE2
17 participants
Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12
2020-10-23
Participant Flow
This was a double-blind, placebo-controlled, parallel group study conducted in participants with moderate to severe asthma with allergic fungal airway disease (AFAD). The study was conducted across 4 countries-France, Netherlands, Russian Federation and the United Kingdom.
A total of 17 participants were randomized in a ratio of 1:1 to receive either GSK3772847 10 milligrams per kilogram (mg/kg) or placebo. Recruitment in the study was terminated early due to the feasibility of completing the study in a timely manner.
Participant milestones
| Measure |
Placebo
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)
Baseline characteristics by cohort
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.9 Years
STANDARD_DEVIATION 9.57 • n=5 Participants
|
53.6 Years
STANDARD_DEVIATION 12.59 • n=7 Participants
|
56.9 Years
STANDARD_DEVIATION 11.21 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian-Japanese/East Asian (EA)/South EA Heritage
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12Population: Modified Intent-to-Treat (mITT) Population comprised of all randomized participants who took at least 1 dose of study treatment. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Blood samples were collected at the indicated time points for assessment of blood eosinophil cell count. Baseline is the most recent recorded value before dosing on Day 1. Percent change from Baseline is calculated as (Ratio to Baseline minus 1)\*100, where ratio to Baseline is the value at specified time point divided by Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Percent Change From Baseline in Blood Eosinophils Over Time
Week 2; n=9, 8
|
30.8 Percent change
Interval 4.0 to 61.0
|
28.1 Percent change
Interval -46.0 to 550.0
|
|
Percent Change From Baseline in Blood Eosinophils Over Time
Week 4; n=8, 8
|
16.0 Percent change
Interval -17.0 to 77.0
|
2.1 Percent change
Interval -71.0 to 469.0
|
|
Percent Change From Baseline in Blood Eosinophils Over Time
Week 8; n=8, 8
|
14.4 Percent change
Interval -98.0 to 262.0
|
-31.4 Percent change
Interval -59.0 to 10.0
|
|
Percent Change From Baseline in Blood Eosinophils Over Time
Week 12; n=5, 7
|
9.7 Percent change
Interval -88.0 to 67.0
|
-10.9 Percent change
Interval -76.0 to 469.0
|
PRIMARY outcome
Timeframe: Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
FeNO was assessed using a handheld electronic device. The measurements were obtained in accordance with 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. Participants did not use their rescue medication for at least 6 hours before each FeNO assessment, unless essential for clinical need. Baseline is the most recent recorded value before dosing on Day 1. Percent change from Baseline is calculated as (Ratio to Baseline minus 1)\*100, where ratio to Baseline is the value at specified time point divided by Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Over Time
Week 2; n=9, 6
|
33.4 Percent change
Interval -39.0 to 51.0
|
-18.6 Percent change
Interval -37.0 to 12.0
|
|
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Over Time
Week 4; n=8, 8
|
13.7 Percent change
Interval -29.0 to 205.0
|
-12.5 Percent change
Interval -48.0 to 36.0
|
|
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Over Time
Week 8; n=8, 7
|
11.7 Percent change
Interval -80.0 to 75.0
|
-42.8 Percent change
Interval -67.0 to 5.0
|
|
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Over Time
Week 12; n=5, 6
|
-37.2 Percent change
Interval -65.0 to -16.0
|
-45.6 Percent change
Interval -68.0 to -34.0
|
SECONDARY outcome
Timeframe: Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose), Week 12 and Week 24Population: Pharmacokinetic (PK) Population comprised of all randomized participants who received at least one dose of study medication, and for whom at least one pharmacokinetic sample was obtained, analyzed and was measurable.
Whole blood samples were collected at indicated time points for measurement of serum concentrations of GSK3772847.
Outcome measures
| Measure |
Placebo
n=8 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Serum Concentrations of GSK3772847
Week 0, post-dose
|
156.50 Micrograms per milliliter
Standard Deviation 74.102
|
—
|
|
Serum Concentrations of GSK3772847
Week 2
|
65.35 Micrograms per milliliter
Standard Deviation 10.900
|
—
|
|
Serum Concentrations of GSK3772847
Week 4, pre-dose
|
39.13 Micrograms per milliliter
Standard Deviation 10.777
|
—
|
|
Serum Concentrations of GSK3772847
Week 8, pre-dose
|
56.24 Micrograms per milliliter
Standard Deviation 9.658
|
—
|
|
Serum Concentrations of GSK3772847
Week 8, post-dose
|
209.61 Micrograms per milliliter
Standard Deviation 93.217
|
—
|
|
Serum Concentrations of GSK3772847
Week 12
|
68.59 Micrograms per milliliter
Standard Deviation 15.570
|
—
|
|
Serum Concentrations of GSK3772847
Week 24
|
1.67 Micrograms per milliliter
Standard Deviation 1.276
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Serum samples were collected at indicated time points for assessment of free ST2 levels. Baseline is the most recent recorded value before dosing on Day 1 (Week 0).
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Baseline; n=9, 8
|
2.365 Micrograms per liter
Geometric Coefficient of Variation 54.3
|
2.418 Micrograms per liter
Geometric Coefficient of Variation 50.0
|
|
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Week 0 (post-dose); n=9, 8
|
2.301 Micrograms per liter
Geometric Coefficient of Variation 46.9
|
0.025 Micrograms per liter
Geometric Coefficient of Variation 668.2
|
|
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Week 2; n=9, 8
|
2.286 Micrograms per liter
Geometric Coefficient of Variation 50.2
|
0.156 Micrograms per liter
Geometric Coefficient of Variation 43.4
|
|
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Week 4 (pre-dose); n=8, 8
|
2.382 Micrograms per liter
Geometric Coefficient of Variation 32.1
|
0.197 Micrograms per liter
Geometric Coefficient of Variation 44.0
|
|
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Week 8 (pre-dose); n=8, 8
|
2.563 Micrograms per liter
Geometric Coefficient of Variation 30.8
|
0.181 Micrograms per liter
Geometric Coefficient of Variation 25.8
|
|
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Week 8 (post-dose); n=8, 8
|
2.568 Micrograms per liter
Geometric Coefficient of Variation 33.7
|
0.126 Micrograms per liter
Geometric Coefficient of Variation 38.2
|
|
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Week 12; n=5, 6
|
2.194 Micrograms per liter
Geometric Coefficient of Variation 46.5
|
0.144 Micrograms per liter
Geometric Coefficient of Variation 67.3
|
SECONDARY outcome
Timeframe: Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Serum samples were collected at indicated time points for assessment of total soluble ST2 levels. Baseline is the most recent recorded value before dosing on Day 1 (Week 0).
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Serum Levels of Total Soluble ST2
Baseline; n=9, 8
|
1.905 Micrograms per liter
Geometric Coefficient of Variation 71.4
|
2.382 Micrograms per liter
Geometric Coefficient of Variation 51.1
|
|
Serum Levels of Total Soluble ST2
Week 0 (post-dose); n=9, 8
|
1.884 Micrograms per liter
Geometric Coefficient of Variation 60.4
|
3.258 Micrograms per liter
Geometric Coefficient of Variation 39.6
|
|
Serum Levels of Total Soluble ST2
Week 2; n=9, 8
|
1.777 Micrograms per liter
Geometric Coefficient of Variation 65.5
|
63.353 Micrograms per liter
Geometric Coefficient of Variation 44.7
|
|
Serum Levels of Total Soluble ST2
Week 4 (pre-dose); n=8, 8
|
1.950 Micrograms per liter
Geometric Coefficient of Variation 35.6
|
65.833 Micrograms per liter
Geometric Coefficient of Variation 47.3
|
|
Serum Levels of Total Soluble ST2
Week 8 (pre-dose); n=8, 8
|
2.141 Micrograms per liter
Geometric Coefficient of Variation 39.9
|
79.286 Micrograms per liter
Geometric Coefficient of Variation 31.6
|
|
Serum Levels of Total Soluble ST2
Week 8 (post-dose); n=8, 8
|
2.201 Micrograms per liter
Geometric Coefficient of Variation 40.7
|
74.046 Micrograms per liter
Geometric Coefficient of Variation 44.7
|
|
Serum Levels of Total Soluble ST2
Week 12; n=5, 6
|
1.900 Micrograms per liter
Geometric Coefficient of Variation 61.3
|
75.703 Micrograms per liter
Geometric Coefficient of Variation 54.1
|
SECONDARY outcome
Timeframe: Weeks 0, 2, 4, 8, 12 and 24Population: Safety Population consisted of all randomized participants who took at least 1 dose of study treatment. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3772847. The presence of anti-GSK3772847 antibodies was assessed using a tiered approach including a screening assay, a confirmation assay and calculation of titre. Data for participants who showed positive results for confirmation assay has been presented.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
Week 0; n=9, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
Week 2; n=9, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
Week 4; n=8, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
Week 8; n=8, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
Week 12; n=8, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
Week 24; n=9, 8
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Weeks 0, 2, 4, 8, 12 and 24Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3772847. The presence of anti-GSK3772847 antibodies was assessed using a tiered approach including a screening assay, a confirmation assay and calculation of titer. Data for number of participants for whom titers of anti-GSK3772847 antibodies was performed is presented.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
Week 0; n=9, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
Week 2; n=9, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
Week 4; n=8, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
Week 8; n=8, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
Week 12; n=8, 8
|
0 Participants
|
0 Participants
|
|
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
Week 24; n=9, 8
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Weeks 2, 4, 8 and 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
The ACQ-5 is a five-item, self-completed questionnaire, which measures a participant's asthma control. The questions enquire about the frequency and/or severity of symptoms (nocturnal awakening, activity limitation, shortness of breath and wheeze) 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 is the mean of the five questions and ranges from 0 (totally controlled) to 6 (severely uncontrolled). Baseline value is defined as the ACQ-5 assessment on Day 1. Change from Baseline is calculated as the post-dose value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Absolute Score at Weeks 2, 4, 8 and 12
Week 2; n=9, 8
|
-0.47 Scores on a scale
Standard Deviation 0.616
|
-0.65 Scores on a scale
Standard Deviation 0.739
|
|
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Absolute Score at Weeks 2, 4, 8 and 12
Week 4; n=8, 8
|
-0.23 Scores on a scale
Standard Deviation 1.087
|
-1.03 Scores on a scale
Standard Deviation 0.897
|
|
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Absolute Score at Weeks 2, 4, 8 and 12
Week 8; n=8, 8
|
-0.60 Scores on a scale
Standard Deviation 0.986
|
-1.23 Scores on a scale
Standard Deviation 1.383
|
|
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Absolute Score at Weeks 2, 4, 8 and 12
Week 12; n=5, 7
|
-0.12 Scores on a scale
Standard Deviation 1.262
|
-1.20 Scores on a scale
Standard Deviation 1.095
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Weeks 2, 4, 8 and 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
The AQLQ is a disease-specific, self-administered quality of life questionnaire that was developed to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ contains 32 items in four domains: activity limitation (11 items), symptoms (12 items), emotional function (five items), and environmental stimuli (four items). Participants were asked to recall their experience over the previous 14 days and respond to each question on a seven-point scale where a value of 1 indicates 'total impairment' and 7 indicates 'no impairment'. The total score is the mean of responses to all 32 questions and each individual domain score was calculated as the mean of the items within that domain. Hence, the total and domain scores were each defined on a range from 1 to 7 with higher scores indicating a higher quality of life. Baseline value is defined as the AQLQ assessment on Day 1. Change from Baseline is calculated as the post-dose value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Total score: Week 2; n=9, 8
|
0.31 Scores on a scale
Standard Deviation 0.660
|
0.45 Scores on a scale
Standard Deviation 0.623
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Total score: Week 4; n=8, 8
|
-0.22 Scores on a scale
Standard Deviation 0.477
|
0.56 Scores on a scale
Standard Deviation 0.514
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Total score: Week 8; n=8, 8
|
0.27 Scores on a scale
Standard Deviation 0.846
|
1.09 Scores on a scale
Standard Deviation 0.940
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Total score: Week 12; n=5, 7
|
0.10 Scores on a scale
Standard Deviation 1.394
|
1.13 Scores on a scale
Standard Deviation 0.953
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Activity limitation; Week 2; n=9, 8
|
0.20 Scores on a scale
Standard Deviation 0.504
|
0.31 Scores on a scale
Standard Deviation 0.750
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Activity limitation; Week 4; n=8, 8
|
-0.26 Scores on a scale
Standard Deviation 0.499
|
0.30 Scores on a scale
Standard Deviation 0.570
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Symptoms; Week 4; n=8, 8
|
-0.05 Scores on a scale
Standard Deviation 0.774
|
0.74 Scores on a scale
Standard Deviation 0.627
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Activity limitation; Week 8; n=8, 8
|
0.12 Scores on a scale
Standard Deviation 0.603
|
0.88 Scores on a scale
Standard Deviation 0.900
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Activity limitation; Week 12; n=5, 7
|
-0.07 Scores on a scale
Standard Deviation 1.127
|
0.91 Scores on a scale
Standard Deviation 0.993
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Symptoms; Week 2; n=9, 8
|
0.52 Scores on a scale
Standard Deviation 0.924
|
0.54 Scores on a scale
Standard Deviation 0.641
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Symptoms; Week 8; n=8, 8
|
0.57 Scores on a scale
Standard Deviation 1.213
|
1.24 Scores on a scale
Standard Deviation 0.936
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Symptoms; Week 12; n=5, 7
|
0.52 Scores on a scale
Standard Deviation 1.740
|
1.31 Scores on a scale
Standard Deviation 0.810
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Environmental stimuli; Week 2; n=9, 8
|
-0.14 Scores on a scale
Standard Deviation 0.811
|
0.22 Scores on a scale
Standard Deviation 0.891
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Environmental stimuli; Week 4; n=8, 8
|
-0.44 Scores on a scale
Standard Deviation 0.884
|
0.63 Scores on a scale
Standard Deviation 0.886
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Environmental stimuli; Week 8; n=8, 8
|
-0.44 Scores on a scale
Standard Deviation 1.208
|
1.06 Scores on a scale
Standard Deviation 1.132
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Environmental stimuli; Week 12; n=5, 7
|
-0.65 Scores on a scale
Standard Deviation 1.025
|
0.89 Scores on a scale
Standard Deviation 1.257
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Emotional function; Week 2; n=9, 8
|
0.40 Scores on a scale
Standard Deviation 0.860
|
0.75 Scores on a scale
Standard Deviation 0.955
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Emotional function; Week 4; n=8, 8
|
-0.35 Scores on a scale
Standard Deviation 0.833
|
0.65 Scores on a scale
Standard Deviation 0.847
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Emotional function; Week 8; n=8, 8
|
0.45 Scores on a scale
Standard Deviation 1.165
|
1.22 Scores on a scale
Standard Deviation 1.289
|
|
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Emotional function; Week 12; n=5, 7
|
0.08 Scores on a scale
Standard Deviation 1.712
|
1.37 Scores on a scale
Standard Deviation 1.246
|
SECONDARY outcome
Timeframe: Weeks 2, 4, 8 and 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
The ACQ-5 is a five-item, self-completed questionnaire, which measures a participant's asthma control. The questions enquire about the frequency and/or severity of symptoms (nocturnal awakening, activity limitation, shortness of breath and wheeze) 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 is the mean of the five questions and ranges from 0 (totally controlled) to 6 (severely uncontrolled). A responder to ACQ-5 is defined as a participant who has a decrease from Baseline in ACQ-5 score of 0.5 or more at Weeks 2, 4, 8 and 12.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Percentage of Responders to ACQ-5 at Weeks 2, 4, 8 and 12
Week 8; n=8, 8
|
50 Percentage of responders
|
50 Percentage of responders
|
|
Percentage of Responders to ACQ-5 at Weeks 2, 4, 8 and 12
Week 2; n=9, 8
|
44 Percentage of responders
|
50 Percentage of responders
|
|
Percentage of Responders to ACQ-5 at Weeks 2, 4, 8 and 12
Week 4; n=8, 8
|
63 Percentage of responders
|
50 Percentage of responders
|
|
Percentage of Responders to ACQ-5 at Weeks 2, 4, 8 and 12
Week 12; n=5, 7
|
20 Percentage of responders
|
71 Percentage of responders
|
SECONDARY outcome
Timeframe: Weeks 2, 4, 8 and 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
The AQLQ is a disease-specific, self-administered quality of life questionnaire that was developed to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ contains 32 items in four domains: activity limitation (11 items), symptoms (12 items), emotional function (five items), and environmental stimuli (four items). Participants were asked to recall their experience over the previous 14 days and respond to each question on a seven-point scale where a value of 1 indicates 'total impairment' and 7 indicates 'no impairment'. The total score is the mean of responses to all 32 questions. The total score was defined on a range from 1 to 7 with higher scores indicating a higher quality of life. A responder to AQLQ is defined as a participant who has an increase from Baseline in AQLQ score of 0.5 or more at Weeks 2, 4, 8 and 12.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Percentage of Responders to AQLQ at Weeks 2, 4, 8 and 12
Week 2; n=9, 8
|
44 Percentage of responders
|
50 Percentage of responders
|
|
Percentage of Responders to AQLQ at Weeks 2, 4, 8 and 12
Week 4; n=8, 8
|
0 Percentage of responders
|
38 Percentage of responders
|
|
Percentage of Responders to AQLQ at Weeks 2, 4, 8 and 12
Week 8; n=8, 8
|
25 Percentage of responders
|
63 Percentage of responders
|
|
Percentage of Responders to AQLQ at Weeks 2, 4, 8 and 12
Week 12; n=5, 7
|
40 Percentage of responders
|
86 Percentage of responders
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 is measured using spirometry. Baseline is the most recent recorded value before dosing on Day 1. Change from Baseline is calculated as the post-dose value minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 2; n=9, 8
|
0.076 Liters
Standard Deviation 0.3383
|
-0.137 Liters
Standard Deviation 0.2640
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 4; n=7, 8
|
-0.049 Liters
Standard Deviation 0.2304
|
-0.022 Liters
Standard Deviation 0.2703
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 8; n=7, 7
|
0.060 Liters
Standard Deviation 0.4210
|
0.040 Liters
Standard Deviation 0.2381
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 12; n=5, 7
|
0.102 Liters
Standard Deviation 0.4879
|
-0.013 Liters
Standard Deviation 0.1923
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12Population: mITT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
FVC is the maximal amount of air that can be forcibly exhaled from lungs after taking the deepest breath possible. FVC is measured by spirometry. Baseline is the most recent recorded value before dosing on Day 1. Change from Baseline is calculated as the post-dose value minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 2; n=9, 8
|
0.078 Liters
Standard Deviation 0.4201
|
-0.074 Liters
Standard Deviation 0.3761
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 4; n=7, 8
|
0.091 Liters
Standard Deviation 0.3163
|
0.090 Liters
Standard Deviation 0.3049
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 8; n=7, 7
|
0.179 Liters
Standard Deviation 0.5145
|
0.030 Liters
Standard Deviation 0.2291
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 12; n=5, 7
|
0.136 Liters
Standard Deviation 0.5351
|
0.050 Liters
Standard Deviation 0.2408
|
SECONDARY outcome
Timeframe: Up to Week 24Population: Safety Population
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
7 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 24Population: Safety Population
Blood samples were collected for the assessment of following clinical chemistry parameters: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, carbon dioxide, chloride, creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase, glucose, phosphate, potassium, protein, sodium and urea. Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 percent (%). 'To Low' rows are not presented for tests that have lower limit of normal = 0.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Alanine aminotransferase; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Alanine aminotransferase; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Albumin; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Albumin; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Albumin; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Alkaline Phosphatase; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Alkaline Phosphatase; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Alkaline Phosphatase; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Aspartate Aminotransferase; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Aspartate Aminotransferase; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Bilirubin; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Bilirubin; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Calcium; To low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Calcium; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Calcium; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Carbon Dioxide; To low
|
2 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Carbon Dioxide; To normal or no change
|
7 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Carbon Dioxide; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Chloride; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Chloride; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Chloride; To high
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Creatine Kinase; To normal or no change
|
7 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Creatine Kinase; To high
|
2 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Creatinine; To low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Creatinine; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Creatinine; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Direct Bilirubin; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Direct Bilirubin; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Gamma Glutamyl Transferase; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Gamma Glutamyl Transferase; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Glucose; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Glucose; To normal or no change
|
7 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Glucose; To high
|
2 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Phosphate; To low
|
2 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Phosphate; To normal or no change
|
5 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Phosphate; To high
|
2 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Potassium; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Potassium; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Potassium; To high
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Protein; To low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Protein; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Protein; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Sodium; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Sodium; To normal or no change
|
8 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Sodium; To high
|
1 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Urea; To low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Urea; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Urea; To high
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 24Population: Safety Population
Blood samples were collected for the assessment of following hematology parameters: basophils, eosinophils, erythrocyte (Ery. ) mean hemoglobin concentration (MCHC), Ery. mean corpuscular hemoglobin (MCH), Ery mean corpuscular volume (MCV), erythrocytes, erythrocytes distribution width, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. 'To Low' rows are not presented for tests that have lower limit of normal = 0.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Lymphocytes; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Basophils; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Basophils; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Eosinophils; To low
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Eosinophils; To normal or no change
|
5 Participants
|
6 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Eosinophils; To high
|
3 Participants
|
2 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCHC; To low
|
4 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCHC; To normal or no change
|
5 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCHC; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCH; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCH; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCH; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCV; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCV; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Ery. MCV; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Erythrocytes; To low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Erythrocytes; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Erythrocytes; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
EDW; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
EDW; To normal or no change
|
7 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
EDW; To high
|
2 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Hematocrit; To low
|
1 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Hematocrit; To normal or no change
|
8 Participants
|
6 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Hematocrit; To high
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Hemoglobin; To low
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Hemoglobin; To normal or no change
|
8 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Hemoglobin; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Leukocytes; To low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Leukocytes; To normal or no change
|
9 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Leukocytes; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Lymphocytes; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Lymphocytes To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Monocytes; To low
|
1 Participants
|
2 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Monocytes; To normal or no change
|
8 Participants
|
6 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Monocytes; To high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Neutrophils; To low
|
1 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Neutrophils; To normal or no change
|
7 Participants
|
7 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Neutrophils; To high
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Platelets; To low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Platelets; To normal or no change
|
9 Participants
|
8 Participants
|
|
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Platelets; To high
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), Week 0 (post-dose), Weeks 4 and 8 (pre-dose and post-dose) Weeks 12 and 24Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
SBP and DBP were measured in the supine position after five minutes of rest for the participant. Baseline is the most recent recorded value before dosing on Day 1 (Week 0). Change from Baseline is calculated as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; Week 0 (post-dose); n=9, 8
|
3.7 Millimeters of mercury
Standard Deviation 8.77
|
1.4 Millimeters of mercury
Standard Deviation 9.38
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; Week 4 (pre-dose); n=8, 8
|
0.1 Millimeters of mercury
Standard Deviation 14.40
|
-2.5 Millimeters of mercury
Standard Deviation 18.05
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; Week 4 (post-dose); n=8, 8
|
4.5 Millimeters of mercury
Standard Deviation 14.16
|
4.5 Millimeters of mercury
Standard Deviation 19.18
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; Week 8 (pre-dose); n=8, 8
|
0.5 Millimeters of mercury
Standard Deviation 14.42
|
7.3 Millimeters of mercury
Standard Deviation 17.81
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; Week 8 (post-dose); n=8, 8
|
0.6 Millimeters of mercury
Standard Deviation 15.27
|
6.0 Millimeters of mercury
Standard Deviation 18.97
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; Week 12; n=8, 8
|
4.1 Millimeters of mercury
Standard Deviation 13.17
|
7.1 Millimeters of mercury
Standard Deviation 18.74
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP; Week 24; n=9, 8
|
2.7 Millimeters of mercury
Standard Deviation 17.00
|
6.1 Millimeters of mercury
Standard Deviation 14.97
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; Week 0 (post-dose); n=9, 8
|
0.1 Millimeters of mercury
Standard Deviation 5.40
|
0.6 Millimeters of mercury
Standard Deviation 7.15
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; Week 4 (pre-dose); n=8, 8
|
-3.1 Millimeters of mercury
Standard Deviation 3.72
|
1.0 Millimeters of mercury
Standard Deviation 14.11
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; Week 4 (post-dose); n=8, 8
|
-4.8 Millimeters of mercury
Standard Deviation 4.92
|
1.3 Millimeters of mercury
Standard Deviation 12.90
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; Week 8 (pre-dose); n=8, 8
|
-7.8 Millimeters of mercury
Standard Deviation 8.31
|
0.6 Millimeters of mercury
Standard Deviation 14.23
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; Week 8 (post-dose); n=8, 8
|
-11.3 Millimeters of mercury
Standard Deviation 9.92
|
-1.0 Millimeters of mercury
Standard Deviation 13.63
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; Week 12; n=8, 8
|
-2.9 Millimeters of mercury
Standard Deviation 4.49
|
2.6 Millimeters of mercury
Standard Deviation 12.34
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP; Week 24; n=9, 8
|
-5.2 Millimeters of mercury
Standard Deviation 6.98
|
3.0 Millimeters of mercury
Standard Deviation 14.93
|
SECONDARY outcome
Timeframe: Baseline (Day 1, pre-dose), Week 0 (post-dose), Weeks 4 and 8 (pre-dose and post-dose) Weeks 12 and 24Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Pulse rate was measured in the supine position after five minutes of rest for the participant. Baseline is the most recent recorded value before dosing on Day 1 (Week 0). Change from Baseline is calculated as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Change From Baseline in Pulse Rate
Week 0 (post-dose); n=9, 8
|
-0.8 Beats per minute
Standard Deviation 7.63
|
-2.5 Beats per minute
Standard Deviation 5.37
|
|
Change From Baseline in Pulse Rate
Week 4 (pre-dose); n=8, 8
|
0.8 Beats per minute
Standard Deviation 9.60
|
-1.8 Beats per minute
Standard Deviation 8.17
|
|
Change From Baseline in Pulse Rate
Week 4 (post-dose); n=8, 8
|
-6.8 Beats per minute
Standard Deviation 9.04
|
-1.0 Beats per minute
Standard Deviation 9.80
|
|
Change From Baseline in Pulse Rate
Week 8 (pre-dose); n=8, 8
|
0.0 Beats per minute
Standard Deviation 8.26
|
-1.5 Beats per minute
Standard Deviation 6.55
|
|
Change From Baseline in Pulse Rate
Week 8 (post-dose); n=8, 8
|
-6.3 Beats per minute
Standard Deviation 6.39
|
-2.1 Beats per minute
Standard Deviation 6.22
|
|
Change From Baseline in Pulse Rate
Week 12; n=8, 8
|
1.6 Beats per minute
Standard Deviation 3.66
|
-4.1 Beats per minute
Standard Deviation 6.64
|
|
Change From Baseline in Pulse Rate
Week 24; n=9, 8
|
2.2 Beats per minute
Standard Deviation 6.69
|
-0.4 Beats per minute
Standard Deviation 6.99
|
SECONDARY outcome
Timeframe: Up to Week 12Population: Safety Population
Twelve lead ECGs were obtained using a standardized ECG machine that measured heart rate, PR, QRS, QT and corrected QT interval (QTc). ECG measurements were done with the participant in a supine position having rested in this position for approximately 5 minutes before each reading. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings at worst-case post-Baseline are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst-case post-Baseline is presented.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
NCS
|
6 Participants
|
6 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
CS
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Week 0Population: Safety Population
A Holter monitor is a type of continuous ambulatory ECG device used for quantitative assessment of abnormal rhythm events. Number of participants with abnormal 24-hour Holter findings is presented. Data was summarized for participants with at least 16 hours of data.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 Participants
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Number of Participants With Abnormal 24-hour Holter Findings
|
4 Participants
|
7 Participants
|
Adverse Events
Placebo
GSK3772847
Serious adverse events
| Measure |
Placebo
n=9 participants at risk
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 participants at risk
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
Other adverse events
| Measure |
Placebo
n=9 participants at risk
Participants received three doses of placebo administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
GSK3772847
n=8 participants at risk
Participants received three doses of GSK3772847 10 mg/kg administered intravenously every 4 weeks (Weeks 0, 4 and 8) along with their standard of care treatment.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
22.2%
2/9 • Number of events 2 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
12.5%
1/8 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Infections and infestations
Bronchitis
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/9 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
12.5%
1/8 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Number of events 2 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
12.5%
1/8 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Nervous system disorders
Lethargy
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Nervous system disorders
Sciatica
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Blood and lymphatic system disorders
Anaemia
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Cardiac disorders
Tachycardia
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Eye disorders
Conjunctivitis allergic
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Investigations
Blood creatine phosphokinase increased
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
|
Psychiatric disorders
Alcoholism
|
11.1%
1/9 • Number of events 1 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
0.00%
0/8 • AEs and SAEs were collected from the start of study treatment up to Week 24
AEs and SAEs were collected in the Safety Population which comprised of all randomized participants who took at least 1 dose of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER