Efficacy and Safety Study of GSK3772847 in Subjects With Moderately Severe Asthma

ID: NCT03207243
Status: Recruiting
Phase: Phase 2
Start Date: September 14, 2017
First Submitted: June 29, 2017
Last Updated: February 22, 2018
Results: N/A
Organization: GlaxoSmithKline
Sponsors & Collaborators: GlaxoSmithKline
Location: Australia, Canada, United States
Conditions: Asthma
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Study Description

Brief Summary

GSK3772847, an anti-interleukin (IL)33 receptor monoclonal antibody, is a novel treatment for asthma. This is a phase 2a study which aims to evaluate efficacy, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 in subjects with moderately severe asthma. The study will be conducted in 4 phases including screening, run-in phase, treatment phase and follow-up. In treatment phase, eligible subjects will be randomized to receive either GSK3772847 or placebo administered via intravenous (IV) route every 4 weeks in addition to open-label background therapy of fluticasone propionate/ salmeterol (FP/Sal) 500/50 micrograms (mcg) twice daily. During the treatment phase, the background therapy will be switched to FP 500 mcg for 2 weeks and the dose of FP will be reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation. The total duration of study will be approximately 33 weeks and approximately 148 subjects with moderately severe asthma who are maintained on high-dose of inhaled corticosteroids/ Long-Acting Beta-2-Agonists (ICS/LABA) will be randomized.

Detailed Description

Condition or disease Intervention/treatment Phase

Asthma

Drug: GSK3772847
Other Names
Drug: Placebo
Other Names
Drug: Fluticasone propionate/salmeterol
Other Names
Drug: Fluticasone propionate
Other Names
Phase 2

Tracking Information

First Submitted DateJune 29, 2017
Last Update Posted DateFebruary 22, 2018
Actual Start DateSeptember 14, 2017
Anticipated Completion DateMay 09, 2019
Actual Primary Completion DateFebruary 14, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Number of subjects with loss of asthma control [Time Frame: Up to Week 16]

    Loss of asthma control is defined as Asthma Control Questionnaire (ACQ-5) score increase from Baseline (measured at the end of Run-in) more than or equal to 0.5 point or pre-bronchodilator Forced expiratory volume in 1 second (FEV1) decrease from Baseline (measured at the end of Run-in) more than 7.5 percent or inability to titrate ICS according to the pre-defined schedule or clinically significant asthma exacerbation (requiring oral corticosteroid [OCS] and/or hospitalization).

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Number of subjects with a more than or equal to 0.5 point increase from Baseline in ACQ-5 score [Time Frame: Up to Week 16]

    ACQ-5 is a 5 question tool used to measure attributes of asthma control and the score ranges from 0 to 6 where 0 is no impairment/limitation and 6 is total impairment/limitation.

  • Number of subjects who have a Pre-bronchodilator FEV1 decrease from Baseline more than 7.5 percent [Time Frame: Up to Week 16]

    FEV1 is defined as the volume of air that can be forced out in one second after taking a deep breath. Pre-bronchodilator FEV1 will be measured using spirometry.

  • Number of subjects where ICS can not be titrated in accordance with the pre-defined schedule [Time Frame: Up to Week 16]

    ICS (FP) will be titrated in the treatment phase of the study as per the pre-defined schedule.

  • Number of subjects who have a significant asthma exacerbation [Time Frame: Up to Week 16]

    A clinically significant asthma exacerbation is defined as asthma requiring OCS and/or hospitalization.

  • Time to loss of asthma control [Time Frame: Up to Week 16]

    Loss of asthma control is defined as ACQ-5 score increase from Baseline (measured at the end of Run-in) more than or equal to 0.5 point or pre-bronchodilator FEV1 decrease from Baseline (measured at the end of Run-in) more than 7.5 percent or inability to titrate ICS according to the pre-defined schedule or clinically significant asthma exacerbation (requiring OCS and/or hospitalization).

  • Number of subjects with a clinically significant asthma exacerbation or inability to titrate ICS according to the pre-defined schedule [Time Frame: Up to Week 16]

    A clinically significant asthma exacerbation is defined as asthma requiring OCS and/or hospitalization.

  • Number of hospitalization or emergency room (ER) visits per subject [Time Frame: Up to Week 16]

    The number of hospitalization or ER visits per subjects will be assessed.

  • Mean rate of hospitalization or ER visits [Time Frame: Up to Week 16]

    Mean rate of hospitalization or ER visits will be calculated for each subject.

  • Change from Baseline in ACQ-5 absolute score at each week [Time Frame: Baseline and up to Week 16]

    ACQ-5 is a 5 question tool used to measure attributes of asthma control and the score ranges from zero: no impairment/limitation to six: total impairment/limitation. A score of less than 0.75 indicates well-controlled asthma and a score more than or equal to 1.5 indicates poorly controlled asthma. A change of more than or equal to 0.5 in score suggests a clinically important change in score and will be assessed.

  • Number of subjects with more than or equal to 0.5 point decrease from Baseline in ACQ-5 score at each week [Time Frame: Up to Week 16]

    ACQ-5 is a 5 question tool used to measure attributes of asthma control and the score ranges from zero: no impairment/limitation to six: total impairment/limitation. A change of more than or equal to 0.5 in score suggests a clinically important change in score and will be assessed.

  • Change from Baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 4, 8, 12 and 16 [Time Frame: Baseline and up to Week 16]

    SGRQ is a tool comprising of 50 questions designed to measure Quality of Life in subjects with diseases of airway obstruction, measuring symptoms, impact, and activity. Higher scores indicate worse health status, and a change of 4 points is considered a clinically relevant change. Change from Baseline in SGRQ total score will be assessed.

  • Number of SGRQ responders at Week 4, 8, 12 and 16 [Time Frame: Up to Week 16]

    SGRQ is a tool comprising of 50 questions designed to measure Quality of Life in subjects with diseases of airway obstruction, measuring symptoms, impact, and activity. Higher scores indicate worse health status, and a change of 4 points is considered a clinically relevant change.

  • Change from Baseline in pre-bronchodilator FEV1 [Time Frame: Baseline and up to Week 16]

    FEV1 is defined as the volume of air that can be forced out in one second after taking a deep breath. Pre-bronchodilator FEV1 will be measured using spirometry.

  • Change from Baseline in mean morning expiratory flow (PEF) and mean evening PEF [Time Frame: Baseline and up to Week 16]

    PEF is the maximum speed of expiration of a subject. PEF will be measured each morning and each evening using the PEF/electronic diary (eDiary) device.

  • Change from Baseline in mean daytime asthma symptom score [Time Frame: Baseline and up to Week 16]

    On the evening of Visit 1 and every evening there-after, subjects will answer a question on daytime asthma symptoms on a 5-point scale with 0: no daytime asthma symptoms and 4: very severe daytime asthma symptoms. Results will be recorded the results on an eDiary. Change from Baseline in mean daytime asthma symptom score will be calculated.

  • Change from Baseline in rescue medication use [Time Frame: Baseline and up to Week 16]

    Albuterol/salbutamol will be used as rescue medication. Mean number of inhalations per day of rescue medications will be assessed and results will be recorded in an eDiary.

  • Changes from Baseline in night-time awakenings due to asthma symptoms requiring rescue medication use [Time Frame: Baseline and up to Week 16]

    Subjects will need to answer a question on the occurrences of night-time awakenings due to asthma symptoms every morning and will record the results in an eDiary. If the answer is 'Yes' for night-time awakening, subjects will be asked whether they had used rescue medication.

  • Change from Baseline in fractional exhaled nitric oxide (FeNO) [Time Frame: Baseline and up to Week 16]

    Subjects with asthma have high levels of NO in their exhaled breath. FeNO evaluation is a noninvasive method of measuring airway diseases including asthma. FeNO will be measured using a handheld electronic device pre dose at given time points

  • Number of adverse events (AEs) and serious adverse events (SAEs) [Time Frame: Up to Week 28]

    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

  • Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [Time Frame: Baseline and up to Week 28]

    SBP and DBP will be measured in the supine position after at least 5 minutes of rest at given time points.

  • Change from Baseline in pulse rate [Time Frame: Baseline and up to Week 28]

    Pulse rate will be measured in the supine position after at least 5 minutes of rest at given time points.

  • Change between post-dose and pre-dose in SBP and DBP at Week 0, 4, 8 and 12 [Time Frame: Up to Week 12]

    SBP and DBP will be measured in the supine position after at least 5 minutes of rest at given time points and change between post and pre-dose in SBP and DBP will be measured.

  • Change between post-dose and pre-dose in pulse rate at Week 0, 4, 8 and 12 [Time Frame: Up to Week 12]

    Pulse rate will be measured in the supine position after at least 5 minutes of rest at given time points and change between post and pre-dose in pulse rate will be measured.

  • Change from Baseline in 12-lead Electrocardiogram (ECG) findings at Week 4, 8, 12 and 16 [Time Frame: Baseline and up to Week 16]

    Single 12 lead ECG will be used to measure change from Baseline at given time points.

  • Change between post-dose and pre-dose in 12-lead ECG readings at Week 0, 4, 8 and 12 [Time Frame: Up to Week 12]

    Single 12 lead ECG will be used to measure change from Baseline at given time points change between post and pre-dose in ECG will be measured.

  • Change from Baseline in Holter measurements at Week 4 and 12 [Time Frame: Baseline and up to Week 12]

    Continuous ECG monitoring or Holter measurement will be carried out using the Holter monitors.

  • Change from Baseline in platelet, Red Blood Cell (RBC) and White Blood Cell (WBC) count [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in platelet, RBC and WBC count.

  • Change from Baseline in Hemoglobin level [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in hemoglobin level.

  • Change from Baseline in hematocrit level [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in hematocrit level.

  • Change from Baseline in Mean Corpuscular Hemoglobin (MCH) [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in MCH level.

  • Change from Baseline in Mean Corpuscular Volume (MCV) [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in MCV level.

  • Change from Baseline in Mean corpuscular hemoglobin concentration (MCHC) [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in MCHC level.

  • Change from Baseline in Red cell distribution width (RDW) [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in RDW level.

  • Change from Baseline in Blood Urea Nitrogen (BUN) [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in BUN level.

  • Change from Baseline in Aspartate amino-trasnferase (AST), Alanine amino-trasnferase (ALT), alkaline phosphatase, gamma- Glutamyl transferase (GGT) and creatine phosphokinase (CPK) [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in AST, ALT, alkaline phosphatase, GGT and CPK levels.

  • Change from Baseline in glucose, potassium, sodium and calcium, phosphorus, chloride and carbon dioxide (CO2) [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in glucose, potassium, sodium and calcium, phosphorus, chloride and CO2 levels.

  • Change from Baseline in creatinine, total and direct bilirubin [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in creatinine, total and direct bilirubin levels.

  • Change from Baseline in total protein and albumin [Time Frame: Baseline and up to Week 28]

    Blood samples will be collected at given time points to assess change from Baseline in total protein and albumin levels.

  • Change from Baseline in specific gravity of urine [Time Frame: Baseline and up to Week 28]

    Urine samples will be collected at given time points to assess change from Baseline in specific gravity.

  • Change from Baseline in potential of hydrogen (pH) of urine [Time Frame: Baseline and up to Week 28]

    Urine samples will be collected at given time points to assess change from Baseline in pH of urine.

  • Change from Baseline in glucose, protein, ketone, bilirubin, leukocyte, nitrite and urobilinogen levels in urine [Time Frame: Baseline and up to Week 28]

    Urine samples will be collected at given time points to assess change from Baseline in glucose, protein, ketone, bilirubin, leukocyte, nitrite and urobilinogen levels.

  • Number of incidences and titers of anti- GSK3772847 antibodies [Time Frame: Up to Week 28]

    Blood samples will be collected at given time points and the presence of anti-GSK3772847 antibodies will be assessed using a tiered approach including a screening assay, a confirmation assay and calculation of titer.

  • Serum concentration of GSK3772847 [Time Frame: Week 0 post-dose, Week 1, Week 2, Week 4 and Week 8 pre dose, Week 12 pre and post dose, Week 16, Week 20, Week 24, Week 28]

    Blood sample will be collected at given time points after administration of study treatment to investigate the bioavailability profile of DTG tablet(s) in fasted state.

  • Free and total soluble Suppressor of tumorigenicity 2 (sST2) levels [Time Frame: Up to Week 28]

    Blood samples will be collected at given time points during this study to measure the free and total sST2 levels.

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEfficacy and Safety Study of GSK3772847 in Subjects With Moderately Severe Asthma
Official TitleA Randomized, Double-blind, Parallel Group, Multicenter, Stratified Study Evaluating the Efficacy and Safety of Repeat Doses of GSK3772847 Compared With Placebo in Participants With Moderately Severe Asthma
Brief Summary

GSK3772847, an anti-interleukin (IL)33 receptor monoclonal antibody, is a novel treatment for asthma. This is a phase 2a study which aims to evaluate efficacy, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 in subjects with moderately severe asthma. The study will be conducted in 4 phases including screening, run-in phase, treatment phase and follow-up. In treatment phase, eligible subjects will be randomized to receive either GSK3772847 or placebo administered via intravenous (IV) route every 4 weeks in addition to open-label background therapy of fluticasone propionate/ salmeterol (FP/Sal) 500/50 micrograms (mcg) twice daily. During the treatment phase, the background therapy will be switched to FP 500 mcg for 2 weeks and the dose of FP will be reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation. The total duration of study will be approximately 33 weeks and approximately 148 subjects with moderately severe asthma who are maintained on high-dose of inhaled corticosteroids/ Long-Acting Beta-2-Agonists (ICS/LABA) will be randomized.

Detailed Description

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
148
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Asthma
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: GSK3772847

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

Other Names
Drug: Placebo

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

Other Names
Drug: Fluticasone propionate/salmeterol

FP/Sal 500/50 mcg will be administered via inhalation route twice daily to all subjects.

Other Names
Drug: Fluticasone propionate

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

Other Names
Study Groups/Cohorts
Subjects receiving GSK3772847
Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.

Subjects receiving placebo drug
Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.

Study Arms
Experimental Subjects receiving GSK3772847
Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : GSK3772847
GSK3772847 10 mg/kg will be administered as IV infusion once every 4 weeks to randomized subjects.

Experimental Subjects receiving GSK3772847
Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate/salmeterol
FP/Sal 500/50 mcg will be administered via inhalation route twice daily to all subjects.

Experimental Subjects receiving GSK3772847
Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate
FP 500, 250, 100 or 50 mcg will be administered via inhalation route twice daily to all subjects.

Placebo Comparator Subjects receiving placebo drug
Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate
FP 500, 250, 100 or 50 mcg will be administered via inhalation route twice daily to all subjects.

Placebo Comparator Subjects receiving placebo drug
Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate/salmeterol
FP/Sal 500/50 mcg will be administered via inhalation route twice daily to all subjects.

Placebo Comparator Subjects receiving placebo drug
Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Placebo
Placebo sterile normal saline will be administered as IV infusion once every 4 weeks to randomized subjects.

Arm Intervention/Treatment
Experimental Subjects receiving GSK3772847
Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : GSK3772847
Experimental Subjects receiving GSK3772847
Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate/salmeterol
Experimental Subjects receiving GSK3772847
Eligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate
Placebo Comparator Subjects receiving placebo drug
Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate
Placebo Comparator Subjects receiving placebo drug
Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Fluticasone propionate/salmeterol
Placebo Comparator Subjects receiving placebo drug
Eligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and 500, 250, 100 or 50 mcg of FP twice daily for the rest of treatment phase.
Drug : Placebo

Recruitment Information

Recruitment Status:Recruiting
Enrollment148
Completion DateMay 09, 2019
Eligibility Criteria: Inclusion Criteria:
- Age: At least 18 years of age at the time of signing the informed consent.
- Males and females: A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow highly effective contraceptive methods from 4 weeks prior to the first dose of study medication and until at least 16 weeks after the last dose of study medication and completion of the follow-up visit.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
- A subject with a documented diagnosis of moderate severe asthma based on Global Initiative for Asthma (GINA) 2016 Guidelines, whose asthma has been managed with regular treatment of high dose ICS defined as FP 500 mcg twice daily (i.e. 1000 mcg total daily dose) or equivalent, and LABA for at least 4 months. Additional therapy with a leukotriene receptor antagonist (LTRA) is permissible.
- Airway reversibility of at least 12 percent and 200 milliliter (mL) in FEV1 at Screening (Visit 1), or documented reversibility prior to Screening (Visit 1), or documented history of bronchial hyper reactivity (e.g. fall in FEV1 from baseline of more than or equal to 20percent with standard doses of methacholine or histamine, or more than or equal to 15 percent with standardized hyperventilation, hypertonic saline or mannitol challenge) from a bronchoprovocation study [e.g. methacholine challenge prior to Screening (Visit 1)].
- ACQ-5 score more than or equal to 1.0 and less than 4.0 at Screening (Visit 1).
- Had at least one asthma exacerbation within 12 months prior to screening that required treatment with systemic corticosteroid and/or hospitalization.
- All subjects must be able to replace their current Short-Acting Beta2-Agonists (SABA) treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed, per product label, for the duration of the study.
Randomization inclusion criteria:
- ACQ-5 score more than or equal to 1.0 and less than 4.0 at Visit 2.
- Compliance with completion of the Daily eDiary reporting defined as completion of all questions/assessments on more than or equal to 4 of the last 7 days during the run-in period.

Exclusion Criteria:
- Current smokers or former smokers with a smoking history more than or equal to 10 pack years.
- Presence of a known pre-existing, clinically important respiratory conditions (e.g. pneumonia, pneumothorax, atelectasis segmental or larger, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities) other than asthma.
- A pre-bronchodilator FEV1 less than 50 percent predicted of normal value at Screening (Visit 1).
- Subjects with a diagnosis of malignancy or in the process of investigation for a malignancy. Subjects with carcinoma that have not been in complete remission for at least 5 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the subject has been considered cured by treatment.
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at Screening (Visit 1) or within 3 months prior to first dose of study treatment.
- Site investigators will be provided with ECG over-read conducted by a centralized independent cardiologist, to assist in evaluation of subject eligibility.
- Weight: less than 50 kilograms (kg) and more than 150 kg.
- Regular use of systemic corticosteroids for conditions including asthma within 3 months prior to Screening (Visit 1).
- Subjects with high parasympathetic tone (e.g. trained athletes with baseline bradycardia) or chronic conditions associated with parasympathetic surges (e.g. migraines).
- Other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Screening (Visit 1).
- Clinically significant organic heart disease [e.g. Coronary artery disease (CAD), New York Heart Association (NYHA) Class III/IV heart failure].
- Ongoing infections (i.e. not resolved within 7 days prior to Screening [Visit 1]) or recurrent infections (i.e. requiring treatment for an identical diagnosis within 3 months) requiring systemic antibiotics Known, pre-existing parasitic infestations within 6 months prior to Screening.
- A subject must not have any clinically significant, uncontrolled condition, or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
- A known immunodeficiency such as human immunodeficiency virus infection.
- Subjects with allergy or intolerance to a monoclonal antibody or biologic or to any components of the formulation used in this study.
- Subjects with a history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Screening (Visit 1).
- Subjects who are unable to follow study instructions such as visit schedule, dosing directions, study eDiary completion, or use of a standard metered dose inhaler. Subjects who have known evidence of lack of adherence to controller medication and/or ability to follow physician's recommendations. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
- Subjects who have previously participated in a study of GSK3772847.
- Use of the prohibited medications is not permitted within the defined time intervals prior to Screening (Visit 1) and throughout the study. Potential subjects should not be washed out of their medication solely for the purpose on enrolling in the trial.
- A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub investigator, study coordinator, or employee of the participating investigator.
- In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a diary card/questionnaire.
- Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
Randomization exclusion criteria:
- Evidence of clinically significant abnormal laboratory tests during screening which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality.
- Evidence of clinically significant abnormal ECG findings at Visit 2.
- An abnormal and significant finding from 24-hour Holter monitoring at Screening (Visit 1). Investigators will be provided with Holter reviews conducted by an independent cardiologist to assist in evaluation of subject eligibility.
- Liver function at screening (Visit 1): ALT more than 2 x upper limit of normal (ULN) and bilirubin more than 1.5xULN (isolated bilirubin more than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent); Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Subjects with ongoing asthma exacerbation at the time of Visit 2.
- A pre-bronchodilator FEV1 less than 50 percent predicted of normal value at Visit 2.
- Positive pregnancy test at Visit 0, Screening (Visit 1) or Visit 2.
- Ongoing or recurrent infections requiring systemic antibiotics.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Australia
Canada
United States

Administrative Information

NCT Number:NCT03207243
Other Study ID Numbers
207597
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
GlaxoSmithKline
Collaborators
Not Available
Investigators
Study Director
GSK Clinical Trials
GlaxoSmithKline