A Phase 1, First-time-in-human, Four-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of GSK4527363 in Healthy Participants (Part A), Participants With Active Systemic Lupus Erythematosus (Part B), Healthy Participants of Chinese and Japanese Descent (Part C) and Participants With Interstitial Lung Disease Associated With Connective Tissue Disease (Part D)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 142
- 试验地点
- 28
- 主要终点
- Parts A and C: Number of Participants with Non-serious Adverse Events and Serious Adverse Events
研究概览
简要总结
This study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of GSK4527363 in healthy participants (Part A), participants with active SLE (Part B), healthy participants of Chinese and Japanese descent (Part C), and participants with interstitial lung disease associated with connective tissue disease (Part D)
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)
盲法说明
This will be a double-blind study.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Part A and Part C (Healthy Participants):
- •Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent form
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (vital signs and 12-lead ECG)
- •Part C only: Be of Japanese (Cohort C1) or Chinese (Cohort C2) ancestry i. Born in Japan (Cohort C1) or China mainland, Hong Kong or Taiwan (Cohort C2); and ii. Descendent of 2 ethnic Japanese (Cohort C1) or Chinese (Cohort C2) parents and 4 ethnic grandparents; and iii. Have lived outside Japan (Cohort C1) or China mainland, Hong Kong or Taiwan (Cohort C2) for less than 10 years at the time of screening
- •Body weight greater than or equals to (>=) 45 kilograms (kg)
- •Body mass index (BMI) within the range 18-32 kilograms per square meter (kg/m^2) (inclusive)
- •Male or female of non-childbearing potential
- •For Part B (SLE participants):
- •18 to 65 years of age inclusive, at the time of signing the informed consent form
- •Documented clinical diagnosis of SLE according to the (European alliance of associations of rheumatology [EULAR]/ American College of Rheumatology [ACR] SLE classification criteria)
- •Body weight >= 45 kg
- •BMI within the range 18-32 kg/m^2 (inclusive)
- •Male or female
- •Capable of giving signed informed consent For Part D (CTD-ILD Participants)
- •Participants must be 18 to 65 years of age, at the time of signing the informed consent form
- •Documented clinical diagnosis of specific Connective Tissue Diseases in accordance with internationally recognised classification criteria
- •Documented clinical diagnosis of interstitial lung disease (ILD) as determined by historical High-resolution computed tomography (HRCT)
- •Participants must be on a stable dose of therapy to manage ILD and/or underlying connective tissue disease (CTD)
- •Body weight >= 45 kg
- •BMI within the range 18-32 kg/m^2 (inclusive)
- •Male or female
- •Capable of giving signed informed consent
排除标准
- •For Part A and Part C (Healthy Participants):
- •History or presence or cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders
- •A history of recurrent infections, or treatment of a chronic infection within 3 months prior to the first dose of study drug
- •Any acute infection (including upper respiratory tract infections and urinary tract infections) which has not fully resolved within four weeks before dosing
- •Symptomatic herpes zoster within 3 months prior to screening
- •Have a history of malignancy, or a strong family history of malignancies related to immunosuppression
- •Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions
- •Abnormal blood pressure
- •Evidence of active or latent Tuberculosis (TB)
- •Alanine transaminase (ALT) >=1.1* Upper limit of normal (ULN)
- •Total bilirubin >1.0*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >=1.5*ULN as long as direct bilirubin is less than or equal to (<=)1.5*ULN
- •Presence of Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study intervention
- •Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
- •Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
- •Positive Human immunodeficiency virus (HIV) antibody test at screening
- •Prior medical history of anaphylaxis
- •QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec)
- •Live vaccine(s) within 30 days before the dosing day or plans to receive such vaccines during the study
- •For Part B (SLE participants):
- •Any acute, severe lupus related flare during the Screening Period that needs immediate treatment
- •Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE which, in the opinion of the principal investigator (PI), could confound the results of the clinical study or put the participant at undue risk
- •Have an acute or chronic infection requiring management as follows:
- •i. Currently on any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria ii. A serious infection requiring treatment with antibiotics and/or hospitalization if the last dose of antibiotics or the hospital discharge date was within 60 days of the first day of dosing (Day 1). Prophylactic anti-infective treatment is allowed
- •Evidence of active or latent TB
- •Confirmed Progressive Multifocal Leukoencephalopathy (PML) or unexplained new-onset or deteriorating neurologic signs and symptoms
- •ALT >2*ULN
- •Total bilirubin >1.5*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5*ULN as long as direct bilirubin is >1.5*ULN
- •Presence of HBsAg and/or HBcAb at screening or within 3 months prior to first dose of study intervention
- •Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
- •Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention
- •History or positive test at Screening for HIV
- •QTcF >450 msec
- •Solid or hematological malignancy or a history of malignancy (in the past 5 years) of except for basal cell or squamous cell in situ skin carcinomas, Cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix that have been resected with no evidence of metastatic disease for 3 years
- •Live or live-attenuated vaccine(s) within 30 days prior to Screening
- •For Part D Participants:
- •A diagnosis of: ILD other than CTD-ILD and/or SLE
- •FVC <= 45% predicted at Screening Pulmonary arterial hypertension, as determined by the Investigator, prior to Day 1
- •Major surgery (including joint surgery) within 3 months prior to Screening or planned during the duration of the study
- •Previous or planned major organ transplant (e.g. heart, lung, kidney, liver) or bone marrow transplant (e.g. autologous stem cell transplant)
- •Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to CTD-ILD (i.e., cardiovascular, metabolic, hematologic, GI, hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) which, in the opinion of the PI, could confound the results of the clinical study or put the participant at undue risk
- •Have an acute or chronic infection including requiring management
- •Evidence of active or latent TB
- •Confirmed PML or unexplained new-onset or deteriorating neurologic signs and symptoms
- •ALT >2*ULN
- •Total bilirubin >1.5*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5*ULN as long as direct bilirubin is >1.5*ULN
- •Presence of HBsAg and/or HBcAb at screening or within 3 months prior to first dose of study intervention
- •Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
- •Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention
- •History or positive test at Screening for HIV
- •Solid or hematological malignancy or a history of malignancy (in the past 5 years) of except for basal cell or squamous cell in situ skin carcinomas, CIN or carcinoma in situ of the cervix that have been resected with no evidence of metastatic disease for 3 years
- 另有 1 项未显示
研究组 & 干预措施
Part A: Healthy participants receiving belimumab
干预措施: Belimumab (Drug)
Part C: Healthy Japanese participants receiving GSK4527363
干预措施: GSK4527363 (Drug)
Part B: Participants with SLE receiving belimumab
干预措施: Belimumab (Drug)
Part C: Healthy Japanese participants receiving placebo matching GSK4527363
干预措施: Placebo matching GSK4527363 (Drug)
Part C: Healthy Chinese participants receiving placebo matching GSK4527363
干预措施: Placebo matching GSK4527363 (Drug)
Part A: Healthy participants receiving GSK4527363
干预措施: GSK4527363 (Drug)
Part A: Healthy participants receiving placebo matching GSK4527363
干预措施: Placebo matching GSK4527363 (Drug)
Part B: Participants with SLE receiving GSK4527363
干预措施: GSK4527363 (Drug)
Part C: Healthy Chinese participants receiving GSK4527363
干预措施: GSK4527363 (Drug)
Part D: Participants with CTD-ILD receiving GSK4527363
干预措施: GSK4527363 (Drug)
结局指标
主要结局
Parts A and C: Number of Participants with Non-serious Adverse Events and Serious Adverse Events
时间窗: Up to Week 52
Parts B and D: Number of Participants with Non-serious Adverse Events and Serious Adverse Events
时间窗: Up to Week 68
Parts A and C: Number of Participants with Clinically Significant Changes in Physical Examination, Laboratory Parameters, Vital Signs, and 12 lead Electrocardiogram (ECG) Findings
时间窗: Up to Week 52
Parts B and D: Number of Participants with Clinically Significant Changes in Physical Examination, Laboratory Parameters, Vital Signs, and 12 lead Electrocardiogram (ECG) Findings
时间窗: Up to Week 68
Parts A and C: Number of Participants with Clinically Significant Changes in Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to Week 52
The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. A suicidal ideation score will be calculated based on the maximum suicidal ideation category ranging from 1 to 5. Higher score indicates more suicidal ideation. A clinically important change in the C-SSRS is defined as a total score \>0.
Parts B, and D: Number of Participants with Clinically Significant Changes in Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to Week 68
The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. A suicidal ideation score will be calculated based on the maximum suicidal ideation category ranging from 1 to 5. Higher score indicates more suicidal ideation. A clinically important change in the C-SSRS is defined as a total score \>0.
Parts A, B, C and D: Number of Participants with Non-serious Adverse Events and Serious Adverse Events
时间窗: Up to Week 52
Parts A, B, C and D: Number of Participants with Clinically Significant Changes in Physical Examination, Laboratory Parameters, Vital Signs, and 12 lead Electrocardiogram (ECG) Findings
时间窗: Up to Week 52
Parts A, B, C and D: Number of Participants with Clinically Significant Changes in Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to Week 52
The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. A suicidal ideation score will be calculated based on the maximum suicidal ideation category ranging from 1 to 5. Higher score indicates more suicidal ideation. A clinically important change in the C-SSRS is defined as a total score \>0.
次要结局
- Parts A, B and C: Percentage change from Baseline in cytokine levels(Baseline (Day 1) and up to Week 52)
- Part B and D: Area Under the Concentration-time Curve of GSK4527363(Up to Week 12)
- Part B and D: Maximum Plasma Concentration of GSK4527363(Up to Week 12)
- Parts A and C: Number of Participants with Anti-drug Antibodies (ADAs) Against GSK4527363(Up to Week 52)
- Parts B and D: Number of Participants with Anti-drug Antibodies (ADAs) Against GSK4527363(Up to Week 68)
- Parts A and C: Percentage change from Baseline in cytokine levels(Baseline (Day 1) and up to Week 52)
- Parts B and D: Percentage change from Baseline in cytokine levels(Baseline (Day 1) and up to Week 68)
- Part B and D: Concentration at the end of the First Dosing Interval of GSK4527363(Up to Week 12)
- Part B and D: Area Under the Concentration-time Curve over the First Dosing Interval Between Week (wk) 0 and Week 12 (AUC[0-wk12]) of GSK4527363(Up to Week 12)
- Part B and D: Maximum Plasma Concentration Over the First Dosing Interval Between Week 0 and Week 12 (Cmax [0-wk12]) of GSK4527363(Up to Week 12)
- Part B and D: Concentration at the end of the First Dosing Interval at Week 12 (Cwk12) of GSK4527363(Up to Week 12)
- Parts A and C: Area Under the Concentration-time Curve to the Last Quantifiable Concentration (AUC[0-t]) of GSK4527363(Up to Week 52)
- Parts A and C: Area Under the Concentration-time Curve to Infinity (AUC[0-inf]) of GSK4527363(Up to Week 52)
- Parts A and C: Maximum Plasma Concentration (Cmax) of GSK4527363(Up to Week 52)
- Parts A and C: Apparent Terminal Phase Half-life (t1/2) of GSK4527363(Up to Week 52)
- Parts A, B and C: Number of Participants with Anti-drug Antibodies (ADAs) Against GSK4527363(Up to Week 52)
- Parts A, B and C: Titers of ADAs Against GSK4527363(Up to Week 52)