Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)
Primary Purpose
Asthma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GSK3772847
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring Asthma Control Questionnaire, Allergic fungal airway disease, Asthma Quality of Life Questionnaire, Holter monitoring, Asthma
Eligibility Criteria
Inclusion Criteria:
- Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
- Documented history of physician diagnosed moderate or severe asthma for >=12 months based on Guidelines and treated with inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) for at least 4 months (>=500 micrograms/day [µg/day]) fluticasone propionate or equivalent as defined in the guidelines.
- Pre-bronchodilator FEV1 35-79% of predicted value for participant inclusive
- FeNO >= 25 parts per billion (ppb) at Screening
- ACQ-5 score >= 1.5 at Screening
- Blood eosinophil >=300 cells/microliter at Screening
- Evidence of allergic fungal airway disease like Fungal sensitization to any of the fungi Aspergillus fumigatus, Penicillium chrysogenum (notatum) at screening measured by serum-specific Immunoglobulin (Ig) E test. A history of exacerbations with at least 1 severe exacerbation (defined as requiring a minimum of 3 days of high-dose oral corticosteroids for asthma symptoms) in the previous 12 months.
- Body weight within 50-150 kilogram (kg)
- Both male and female gender. A female participant is eligible to participate if she is not pregnant not breastfeeding, Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 16 weeks after the last dose of study treatment.
- Capable of giving signed informed consent
Exclusion Criteria:
- Historical diagnosis of cystic fibrosis
- Concurrent respiratory diseases: Presence of a known pre-existing, clinically important respiratory conditions (example pneumonia, pneumothorax, atelectasis segmental or larger, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities) other than asthma or AFAD
- Has a history of chronic or recurrent non-pulmonary infectious disease or ongoing non-pulmonary infection including, but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (example, recurrent pyelonephritis, chronic non-remitting cystitis), or open, draining skin wound or an ulcer
- Serious infection within 8 weeks of enrolment, including, but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis; or has been hospitalized for an infection; or has been treated with IV antibiotics for an infection, within 8 weeks prior to the first administration of study drug.
- Evidence of poorly controlled chronic medical conditions other than asthma, example, participants with known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, cardiovascular, gastrointestinal, hepatic, and hematological or any other system abnormalities that are uncontrolled with standard treatment.
- Cardiovascular disease: Clinically significant organic heart disease
- Participants with a diagnosis of malignancy or in the process of investigation for a malignancy. Participants with carcinoma that have not been in complete remission for at least 5 years. Participants who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the participant has been considered cured by treatment.
- Eosinophilic diseases: Other conditions that could lead to elevated eosinophil such as hyper-eosinophilic syndromes. Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening (Visit 1)
- Prohibited medications is not permitted within the defined time intervals prior to Screening (Visit 1) and throughout the study.
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
- A known immunodeficiency such as human immunodeficiency virus infection.
- Hypersensitivity: significant allergies to humanized monoclonal antibodies or biologic or to any components of the formulation used in this study
- Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear Ig A dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
- Clinically significant abnormality on 12-lead ECG assessment at screening (Visit 1). Site investigators will be provided with ECG over-read conducted by a centralized independent cardiologist, to assist in evaluation of participant eligibility.
- Sinus bradycardia <45 beats per minute (bpm), sinus tachycardia >= 110 bpm, multifocal atrial tachycardia (wandering atrial pacemaker with rate >100bpm), evidence of Mobitz II second degree or third degree atrioventricular (AV) block, pathological Q waves (defined as wide [>0.04 seconds] and deep [>0.4 millivolts (mV) (4 millimeter [mm] with 10mm/mV setting)] or >25% of the height of the corresponding R wave, providing the R wave was >0.5mV [5mm with 10mm/mV setting], appearing in at least two contiguous leads, evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal premature ventricular complexes, for participants without complete right bundle branch block: QTc for heart rate by Fridericia's formula QTc(F) >= 450 millisecond (msec) or an ECG that is unsuitable for QT measurements, for participants with complete right bundle branch block: QTc(F) >=480 msec or an ECG that is unsuitable for QT measurements, ST-T wave abnormalities, clinically significant conduction abnormalities and clinically significant arrhythmias.
- Smoking history: current smokers or former smokers with a smoking history >= 10 pack years
- History of alcohol or illegal substance abuse within 2 years prior to Screening (Visit1).
- Participants at risk of non-compliance, or unable to comply with the study procedures. Participants who are unable to follow study instructions such as visit schedule and paper diary completion. Participants who have known evidence of lack of adherence to controller medication and/or ability to follow physician's recommendations. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Participants receiving GSK3772847
Participants receiving placebo
Arm Description
Participants will be randomized to receive GSK3772847 as IV infusion. Participants will receive three doses ( Day 1, Day 29 and Day 57) of GSK3772847 every 4 weeks
Participants will be randomized to receive matching placebo as IV infusion
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Blood Eosinophils Over Time
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.
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Over Time
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.
Secondary Outcome Measures
Serum Concentrations of GSK3772847
Whole blood samples were collected at indicated time points for measurement of serum concentrations of GSK3772847.
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
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).
Serum Levels of Total Soluble ST2
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).
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
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.
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
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.
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Absolute Score at Weeks 2, 4, 8 and 12
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.
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
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.
Percentage of Responders to ACQ-5 at Weeks 2, 4, 8 and 12
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.
Percentage of Responders to AQLQ at Weeks 2, 4, 8 and 12
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.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
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.
Change From Baseline in Forced Vital Capacity (FVC)
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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
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.
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
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.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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.
Change From Baseline in Pulse Rate
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.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
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.
Number of Participants With Abnormal 24-hour Holter Findings
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03393806
Brief Title
Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)
Official Title
A Double Blind (Sponsor Open) Placebo-controlled, Stratified, Parallel Group Study to Evaluate the Efficacy and Safety of Repeat Doses of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Terminated
Why Stopped
Recruitment was terminated early before meeting target enrolment due to a high screen failure rate and the feasibility of completing the study in a timely way
Study Start Date
April 18, 2018 (Actual)
Primary Completion Date
October 9, 2019 (Actual)
Study Completion Date
January 6, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is multicenter, double-blinded parallel group design, where participants with moderate to severe asthma with AFAD will be enrolled. Participants will receive three doses of 10 milligrams/kilogram (mg/kg) of GSK3772847 every 4 Weeks versus placebo along with standard of care. Participants will be randomized in 1:1 ratio to receive either 10 mg/kg GSK3772847 intravenously (IV) or matching placebo IV. Participants will receive study treatment on Week 0 (Day 1), Week 4 and Week 8. The total duration of the study will be 28 Weeks and approximately 46 participants will be randomized.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma Control Questionnaire, Allergic fungal airway disease, Asthma Quality of Life Questionnaire, Holter monitoring, Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized in a 1:1 ratio to receive either 10 mg/kg GSK3772847 or matching placebo intravenously.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Participants receiving GSK3772847
Arm Type
Experimental
Arm Description
Participants will be randomized to receive GSK3772847 as IV infusion. Participants will receive three doses ( Day 1, Day 29 and Day 57) of GSK3772847 every 4 weeks
Arm Title
Participants receiving placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized to receive matching placebo as IV infusion
Intervention Type
Drug
Intervention Name(s)
GSK3772847
Intervention Description
GSK3772847 will be available as 100 mg/vial, white to yellow, uniform lyophilized cake in a 5 milliliter (mL) clear glass vial with closure sealed by red metal and yellow overseal.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Commercially sourced sterile normal saline will be provided as Placebo
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Blood Eosinophils Over Time
Description
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.
Time Frame
Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12
Title
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Over Time
Description
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.
Time Frame
Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12
Secondary Outcome Measure Information:
Title
Serum Concentrations of GSK3772847
Description
Whole blood samples were collected at indicated time points for measurement of serum concentrations of GSK3772847.
Time Frame
Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose), Week 12 and Week 24
Title
Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)
Description
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).
Time Frame
Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12
Title
Serum Levels of Total Soluble ST2
Description
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).
Time Frame
Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12
Title
Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing
Description
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.
Time Frame
Weeks 0, 2, 4, 8, 12 and 24
Title
Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed
Description
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.
Time Frame
Weeks 0, 2, 4, 8, 12 and 24
Title
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Absolute Score at Weeks 2, 4, 8 and 12
Description
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.
Time Frame
Baseline (Day 1), Weeks 2, 4, 8 and 12
Title
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12
Description
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.
Time Frame
Baseline (Day 1), Weeks 2, 4, 8 and 12
Title
Percentage of Responders to ACQ-5 at Weeks 2, 4, 8 and 12
Description
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.
Time Frame
Weeks 2, 4, 8 and 12
Title
Percentage of Responders to AQLQ at Weeks 2, 4, 8 and 12
Description
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.
Time Frame
Weeks 2, 4, 8 and 12
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Description
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.
Time Frame
Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12
Title
Change From Baseline in Forced Vital Capacity (FVC)
Description
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.
Time Frame
Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Up to Week 24
Title
Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline
Description
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.
Time Frame
Up to Week 24
Title
Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline
Description
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.
Time Frame
Up to Week 24
Title
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description
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.
Time Frame
Baseline (Day 1, pre-dose), Week 0 (post-dose), Weeks 4 and 8 (pre-dose and post-dose) Weeks 12 and 24
Title
Change From Baseline in Pulse Rate
Description
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.
Time Frame
Baseline (Day 1, pre-dose), Week 0 (post-dose), Weeks 4 and 8 (pre-dose and post-dose) Weeks 12 and 24
Title
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description
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.
Time Frame
Up to Week 12
Title
Number of Participants With Abnormal 24-hour Holter Findings
Description
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.
Time Frame
Week 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
Documented history of physician diagnosed moderate or severe asthma for >=12 months based on Guidelines and treated with inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) for at least 4 months (>=500 micrograms/day [µg/day]) fluticasone propionate or equivalent as defined in the guidelines.
Pre-bronchodilator FEV1 35-79% of predicted value for participant inclusive
FeNO >= 25 parts per billion (ppb) at Screening
ACQ-5 score >= 1.5 at Screening
Blood eosinophil >=300 cells/microliter at Screening
Evidence of allergic fungal airway disease like Fungal sensitization to any of the fungi Aspergillus fumigatus, Penicillium chrysogenum (notatum) at screening measured by serum-specific Immunoglobulin (Ig) E test. A history of exacerbations with at least 1 severe exacerbation (defined as requiring a minimum of 3 days of high-dose oral corticosteroids for asthma symptoms) in the previous 12 months.
Body weight within 50-150 kilogram (kg)
Both male and female gender. A female participant is eligible to participate if she is not pregnant not breastfeeding, Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 16 weeks after the last dose of study treatment.
Capable of giving signed informed consent
Exclusion Criteria:
Historical diagnosis of cystic fibrosis
Concurrent respiratory diseases: Presence of a known pre-existing, clinically important respiratory conditions (example pneumonia, pneumothorax, atelectasis segmental or larger, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities) other than asthma or AFAD
Has a history of chronic or recurrent non-pulmonary infectious disease or ongoing non-pulmonary infection including, but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (example, recurrent pyelonephritis, chronic non-remitting cystitis), or open, draining skin wound or an ulcer
Serious infection within 8 weeks of enrolment, including, but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis; or has been hospitalized for an infection; or has been treated with IV antibiotics for an infection, within 8 weeks prior to the first administration of study drug.
Evidence of poorly controlled chronic medical conditions other than asthma, example, participants with known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, cardiovascular, gastrointestinal, hepatic, and hematological or any other system abnormalities that are uncontrolled with standard treatment.
Cardiovascular disease: Clinically significant organic heart disease
Participants with a diagnosis of malignancy or in the process of investigation for a malignancy. Participants with carcinoma that have not been in complete remission for at least 5 years. Participants who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the participant has been considered cured by treatment.
Eosinophilic diseases: Other conditions that could lead to elevated eosinophil such as hyper-eosinophilic syndromes. Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening (Visit 1)
Prohibited medications is not permitted within the defined time intervals prior to Screening (Visit 1) and throughout the study.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
A known immunodeficiency such as human immunodeficiency virus infection.
Hypersensitivity: significant allergies to humanized monoclonal antibodies or biologic or to any components of the formulation used in this study
Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear Ig A dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
Clinically significant abnormality on 12-lead ECG assessment at screening (Visit 1). Site investigators will be provided with ECG over-read conducted by a centralized independent cardiologist, to assist in evaluation of participant eligibility.
Sinus bradycardia <45 beats per minute (bpm), sinus tachycardia >= 110 bpm, multifocal atrial tachycardia (wandering atrial pacemaker with rate >100bpm), evidence of Mobitz II second degree or third degree atrioventricular (AV) block, pathological Q waves (defined as wide [>0.04 seconds] and deep [>0.4 millivolts (mV) (4 millimeter [mm] with 10mm/mV setting)] or >25% of the height of the corresponding R wave, providing the R wave was >0.5mV [5mm with 10mm/mV setting], appearing in at least two contiguous leads, evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal premature ventricular complexes, for participants without complete right bundle branch block: QTc for heart rate by Fridericia's formula QTc(F) >= 450 millisecond (msec) or an ECG that is unsuitable for QT measurements, for participants with complete right bundle branch block: QTc(F) >=480 msec or an ECG that is unsuitable for QT measurements, ST-T wave abnormalities, clinically significant conduction abnormalities and clinically significant arrhythmias.
Smoking history: current smokers or former smokers with a smoking history >= 10 pack years
History of alcohol or illegal substance abuse within 2 years prior to Screening (Visit1).
Participants at risk of non-compliance, or unable to comply with the study procedures. Participants who are unable to follow study instructions such as visit schedule and paper diary completion. Participants who have known evidence of lack of adherence to controller medication and/or ability to follow physician's recommendations. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Brest Cedex
ZIP/Postal Code
29609
Country
France
Facility Name
GSK Investigational Site
City
Montpellier cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
GSK Investigational Site
City
Nantes cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
GSK Investigational Site
City
Izhevsk
ZIP/Postal Code
426063
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Kemerovo
ZIP/Postal Code
650000
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Moscow
ZIP/Postal Code
105275
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Saint Petersburg
ZIP/Postal Code
194291
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Saint Petersburg
ZIP/Postal Code
196240
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Saint-Petersburg
ZIP/Postal Code
194354
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Ulyanovsk
ZIP/Postal Code
432063
Country
Russian Federation
Facility Name
GSK Investigational Site
City
Wythenshawe
State/Province
Greater Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE3 9QP
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Liverpool
State/Province
Merseyside
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Bradford
ZIP/Postal Code
BD9 6RJ
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Edgbaston
ZIP/Postal Code
B15 2GW
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com
Learn more about this trial
Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)
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