A Two-part Phase 1 Randomized, Double-blind, Placebo-controlled Study to Investigate Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of GSK3862995B Following Single Ascending Doses in Healthy Participants and Repeat Doses in Participants With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 127
- 试验地点
- 33
- 主要终点
- Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The primary objective of the study is to investigate the safety and tolerability of ascending doses of GSK3862995B following single dose in healthy participants and repeat doses in participants with Chronic obstructive pulmonary disease (COPD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants (Part A)
- •Participant must be 18 to 65 years of age inclusive.
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
- •Body weight within the range 50-110 kilogram (kg) (inclusive)
- •Body mass index (BMI) within the range 19.5-32 kilogram per square meter (kg/m^2)
- •Male and/or female of non-childbearing potential
- •Participants with Chronic Obstructive Pulmonary Disorder (COPD) (Part B)
- •Participant must be 40 to 75 years of age inclusive.
- •Body weight within the range 50-110 kg (inclusive)
- •BMI within the range 19.5-32 kg/m^2
- •Participant has a confirmed diagnosis of COPD for greater than (>)12 months
- •Participants must present with a measured post-salbutamol Forced expiratory volume in 1 second/Forced vital capacity (FEV1/FVC) ratio of less than (<) 0.70 at screening to confirm the diagnosis of COPD and a measured post-salbutamol FEV1 greater than or equal to (>=) 40% of predicted normal values.
- •Participants must have a well-documented requirement for optimized standard of care background therapy that includes daily inhaled medication.
- •A peripheral blood eosinophil count of >=150 cells/microliter (mcL) at screening
- •Former cigarette smokers with a history of cigarette smoking of >=10 pack-years at screening current smokers (includes the use of any type of nicotine containing product), or non-smokers are permitted
- •Male and/or female of non-childbearing potential.
排除标准
- •Participant has a past or current medical condition(s) or disease(s) that is/are not well controlled and, which in the judgement of the Investigator, may affect participant safety or affect study endpoints.
- •A history of recurrent infections, or treatment of a chronic infection within 3 months prior to the first dose of study drug, including both serious local infection (for example, cellulitis, abscess) or systemic infection (for example, pneumonia, tuberculosis, hepatitis B, shingles).
- •Significant allergies to humanized monoclonal antibodies.
- •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 immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
- •Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- •Breast cancer within the past 10 years
- •Alanine transaminase (ALT) >1x upper limit of normal (ULN)
- •Total bilirubin >1.5xULN (isolated total bilirubin >1.5xULN is acceptable if total bilirubin is fractionated and direct bilirubin less than (<) 35%).
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •A clinically significant abnormality in 12-lead ECG readings performed at screening
- •A clinically significant abnormality in the Holter monitor performed at screening (IV cohorts only).
研究组 & 干预措施
Part B: Placebo
Participants with COPD will receive repeat doses of placebo.
干预措施: Placebo (Drug)
Part A Dose Level 1: Single dose of GSK3862995B
Healthy participants will receive single dose of GSK3862995B.
干预措施: GSK3862995B (Drug)
Part A Dose Level 3: Single dose of GSK3862995B
Healthy participants will receive single dose of GSK3862995B.
干预措施: GSK3862995B (Drug)
Part B: Repeat dose of GSK3862995B
Participants with COPD will receive repeat doses of GSK3862995B.
干预措施: GSK3862995B (Drug)
Part A Dose Level 2: Single dose of GSK3862995B
Healthy participants will receive single dose of GSK3862995B.
干预措施: GSK3862995B (Drug)
Part A Dose Level 4: Single dose of GSK3862995B
Healthy participants will receive single dose of GSK3862995B.
干预措施: GSK3862995B (Drug)
Part A Dose Level 5: Single dose of GSK3862995B
Healthy participants will receive single dose of GSK3862995B.
干预措施: GSK3862995B (Drug)
Part A Dose Level 6: Single dose of GSK3862995B
Healthy participants will receive single dose of GSK3862995B.
干预措施: GSK3862995B (Drug)
Part A: Placebo
Healthy participants will receive single dose of placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 36 weeks
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. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
Part B: Number of Participants with AEs and SAEs
时间窗: Up to 48 weeks
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. Any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persisting disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
Part A: Number of Participants with Clinically significant changes in laboratory values
时间窗: Up to 28 weeks
Number of Participants with clinically significant changes in laboratory values (haematology, chemistry, and urinalysis) will be assessed.
Part A: Number of Participants with Clinically Significant Change in vital signs
时间窗: Up to 28 weeks
Number of participants with clinically significant change in vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure) will be assessed.
Part A: Number of Participants with Clinically Significant Change in 12-lead Electrocardiogram (ECG) Parameters
时间窗: Up to 28 weeks
Number of participants with clinically significant change in 12-lead ECG parameters will be assessed.
Part B: Number of Participants with Clinically significant changes in laboratory values (haematology, chemistry and urinalysis)
时间窗: Up to 42 weeks
Number of Participants with clinically significant changes in laboratory values (haematology, chemistry and urinalysis) will be assessed.
Part B: Number of Participants with Clinically Significant Change in vital signs
时间窗: Up to 42 weeks
Number of participants with clinically significant change in vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure) up to end of intervention period will be assessed.
Part B: Number of Participants with Clinically Significant Change in 12-lead Electrocardiogram (ECG) Parameters
时间窗: Up to 42 weeks
Number of participants with clinically significant change in 12-lead ECG parameters will be assessed.
次要结局
- Part A: Area Under the Concentration-time Curve to the Last Quantifiable Concentration [AUC(0-t)](Up to 28 weeks)
- Part A: Area Under the Concentration-time Curve to the Infinity (inf) [AUC(0-inf)](Up to 28 weeks)
- Part A: Maximum Concentration (Cmax)(Up to 28 weeks)
- Part B: Area Under the Concentration-time Curve Over the Dosing Interval [AUC(0-tau)](Up to 42 weeks)
- Part B: Cmax(Up to 42 weeks)
- Part A: Number of Participants with Anti-Drug Antibodies (ADA) against GSK3682995B(Up to 28 weeks)
- Part B: Number of participants with Incidence of Anti-Drug Antibodies (ADA) against GSK3682995B(Up to 42 weeks)
- Part A: Ratio to Baseline in Absolute and Relative Blood Eosinophil Count(Baseline and up to 28 weeks)
- Part B: Ratio to Baseline in Absolute and Relative Blood Eosinophil Count(Baseline and up to 42 weeks)