NCT03393806终止2 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in Blood Eosinophils Over Time
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Participants receiving GSK3772847
Experimental
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
干预措施: GSK3772847 (Drug)
Participants receiving placebo
Placebo Comparator
Participants will be randomized to receive matching placebo as IV infusion
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline in Blood Eosinophils Over Time
时间窗: Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12
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
时间窗: Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12
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.
次要结局
- Serum Concentrations of GSK3772847(Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose), Week 12 and Week 24)
- Serum Levels of Total Soluble ST2(Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12)
- Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total and Domain Scores at Weeks 2, 4, 8 and 12(Baseline (Day 1), Weeks 2, 4, 8 and 12)
- Percentage of Responders to ACQ-5 at Weeks 2, 4, 8 and 12(Weeks 2, 4, 8 and 12)
- Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)(Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12)
- Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing(Weeks 0, 2, 4, 8, 12 and 24)
- Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed(Weeks 0, 2, 4, 8, 12 and 24)
- Percentage of Responders to AQLQ at Weeks 2, 4, 8 and 12(Weeks 2, 4, 8 and 12)
- Change From Baseline in Forced Vital Capacity (FVC)(Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12)
- Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Absolute Score at Weeks 2, 4, 8 and 12(Baseline (Day 1), Weeks 2, 4, 8 and 12)
- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)(Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline (Day 1, pre-dose), Week 0 (post-dose), Weeks 4 and 8 (pre-dose and post-dose) Weeks 12 and 24)
- Change From Baseline in Pulse Rate(Baseline (Day 1, pre-dose), Week 0 (post-dose), Weeks 4 and 8 (pre-dose and post-dose) Weeks 12 and 24)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Up to Week 12)
- Number of Participants With Worst Case Post-Baseline Chemistry Results Relative to Normal Range at Baseline(Up to Week 24)
- Number of Participants With Abnormal 24-hour Holter Findings(Week 0)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Week 24)
- Number of Participants With Worst Case Post-Baseline Hematology Results Relative to Normal Range at Baseline(Up to Week 24)
研究者
研究点 (1)
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