A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren's Syndrome (pSS)
2018年3月6日 更新者：GlaxoSmithKline
A Two Part Phase IIa Study, to Evaluate the Safety and Tolerability, Pharmacokinetics, Proof of Mechanism and Potential for Efficacy of an Anti-IL-7 Receptor-α Monoclonal Antibody (GSK2618960) in the Treatment of Primary Sjögren's Syndrome
This study aims to evaluate the safety, tolerability and PK of repeat dose administration of GSK2618960 in the treatment of pSS.
The study will contain two parts, Part I will be open label and Part II will be randomized, double-blind.
The minimum duration of Part I & Part II of the study will be 26 and 32 weeks respectively.
研究概览
研究类型
介入性
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Cambridge、英国、CB2 0GG
- GSK Investigational Site
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 70年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Part I and Part II: Male and females aged 18-70
- Part I and Part II: pSS diagnosis according to the American-European Consensus Group Criteria
- Part I and Part II: Documented previous biopsy evidence of salivary gland inflammation consistent with pSS and/or documented history of anti-Ro and/or anti-La antibodies
- Part II: Has any of the following abnormalities at screening: hypergammaglobulinaemia [serum Immunoglobulin G (IgG) greater than or equal to 16 gram per liter (g/L); Presence of Rheumatoid factor (RF); Anti Nuclear Antibodies (ANA) titer greater than or equal to 320:1.
- Stimulated whole salivary flow greater than 0.1 milliliter per minute (mL/min) at screening.
- Symptomatic oral dryness greater than or equal to 5 out of 10 on Visual Analogue Scale (VAS) scale and/or Schirmer test less than 10 millimeter (mm) at screening.
Exclusion Criteria:
- Part I and II: Secondary Sjögren's Syndrome
- Part I and II: Receiving cyclophosphamide, other biologic, immunosuppressive or immunomodulatory treatments
- Part I and II: Active infections, or history of recurrent infections
- Part I and II: History of significant medical illness
- Part I and II: History of lymphoma
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
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GSK2618960 solution for injection, 100mg/mL is clear to opalescent, colorless to yellow or pale brown liquid.
MTX dose between 7.5 to 15 mg will be administered in tablet form once in a week till last dose of GSK2618960 to all subjects in Part I and Part II.
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安慰剂比较：Part II: Placebo
Placebo will be administered IV with MTX
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MTX dose between 7.5 to 15 mg will be administered in tablet form once in a week till last dose of GSK2618960 to all subjects in Part I and Part II.
Placebo solution will be administered by IV infusion.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Number of subjects with Adverse Events (AEs): Part 1
大体时间：Up to Week 29
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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.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
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Up to Week 29
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Number of subjects with abnormal clinical chemistry values: Part 1
大体时间：Up to Week 29
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Samples for clinical chemistry tests will be collected as a measure of safety
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Up to Week 29
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Number of subjects with abnormal hematology values: Part 1
大体时间：Up to Week 29
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Samples for clinical hematology tests will be collected as a measure of safety
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Up to Week 29
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Number of subjects with abnormal urine analysis values: Part 1
大体时间：Up to Week 29
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Samples for Urine analysis tests will be collected as a measure of safety
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Up to Week 29
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Number of subjects with abnormal findings of body temperature: Part 1
大体时间：Up to Week 29
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Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 29
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Number of subjects with abnormal findings of blood pressure: Part 1
大体时间：Up to Week 29
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Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 29
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Number of subjects with abnormal findings of pulse rate: Part 1
大体时间：Up to Week 29
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Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 29
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Number of subjects with abnormal findings of respiratory rate: Part 1
大体时间：Up to Week 29
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Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 29
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Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
大体时间：Up to Week 29
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Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
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Up to Week 29
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Number of subjects with AEs: Part 2
大体时间：Up to Week 35
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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.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
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Up to Week 35
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Number of subjects with abnormal clinical chemistry values: Part 2
大体时间：Up to Week 35
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Samples for clinical chemistry tests will be collected as a measure of safety
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Up to Week 35
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Number of subjects with abnormal hematology values: Part 2
大体时间：Up to Week 35
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Samples for clinical hematology tests will be collected as a measure of safety
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Up to Week 35
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Number of subjects with abnormal urine analysis values: Part 2
大体时间：Up to Week 35
|
Samples for Urine analysis tests will be collected as a measure of safety
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Up to Week 35
|
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Number of subjects with abnormal findings of body temperature: Part 2
大体时间：Up to Week 35
|
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 35
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Number of subjects with abnormal findings of blood pressure: Part 2
大体时间：Up to Week 35
|
SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.
|
Up to Week 35
|
|
Number of subjects with abnormal findings of pulse rate: Part 2
大体时间：Up to Week 35
|
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 35
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Number of subjects with abnormal findings of respiratory rate: Part 2
大体时间：Up to Week 35
|
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
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Up to Week 35
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Number of subjects with abnormal ECG findings: Part 2
大体时间：Up to Week 35
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Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
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Up to Week 35
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Plasma concentration of GSK2618960: Part 1
大体时间：Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
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Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1
大体时间：Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
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Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1
大体时间：Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
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Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Area under the curve (AUC) of GSK2618960: Part 1
大体时间：Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Blood samples will be collected prior to start and at the end of infusion at indicated time points and will be analyzed for PK parameters.
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Day 1: post-infusion; Day 15 and 29: pre-infusion; Day 43: Pre and post-infusion; Day 8, 22, 36, 50, 57, 71, 99 and 127
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Number of incidences of Anti-drug antibody (ADA) formation: Part 1
大体时间：Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Number of titres of ADA: Part 1
大体时间：Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Time to onset of ADA: Part 1
大体时间：Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Number of incidences of ADA neutralization: Part 1
大体时间：Up to Week 29
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 29
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Plasma concentration of GSK2618960 : Part 2
大体时间：Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters
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Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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Cmax of GSK2618960: Part 2
大体时间：Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
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Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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Cmin of GSK2618960: Part 2
大体时间：Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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Blood samples will be collected prior to start and at the end of infusion at the indicated time points and will be analyzed for PK parameters.
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Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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AUC of GSK2618960: Part 2
大体时间：Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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Blood samples will be collected prior to start and at the end of infusion at indicated time points and will be analyzed for PK parameters.
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Day 1: post-infusion; Day 15, 29, 43, 57: pre-infusion; Day 71: Pre and post-infusion; Day 8, 22, 36, 50, 64, 78, 85, 113 and 169
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Number of incidences of ADA formation: Part 2
大体时间：Up to Week 35
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 35
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Number of titres of ADA: Part 2
大体时间：Up to Week 35
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 35
|
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Time to onset of ADA: Part 2
大体时间：Up to Week 35
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
|
Up to Week 35
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Number of incidences of ADA neutralization: Part 2
大体时间：Up to Week 35
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Serum samples will be collected from subjects prior to infusion and various time points post-infusion to carry out immunogenicity and immune-complex analyses.
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Up to Week 35
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Receptor occupancy (RO) on circulating T cells: Part 2
大体时间：Up to Week 35
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Blood samples will be collected from subjects at indicated time points to measure IL-7R alpha occupancy levels.
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Up to Week 35
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Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2
大体时间：Up to Week 35
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Blood samples will be collected from subjects at indicated time points to measure phosphorylation of STAT 5 in response to ex vivo IL-7 stimulation.
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Up to Week 35
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Change from Baseline in Focus score: Part 2
大体时间：Up to Day 29
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Salivary glands for immunohistochemistry analysis will be evaluated for general appearance and total inflammatory infiltrate (focus score).
Salivary gland biopsy will be performed at Baseline and blood samples will be collected at indicated time points.
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Up to Day 29
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2017年9月19日
初级完成 (实际的)
2017年10月12日
研究完成 (预期的)
2017年10月12日
研究注册日期
首次提交
2017年6月19日
首先提交符合 QC 标准的
2017年8月1日
首次发布 (实际的)
2017年8月4日
研究记录更新
最后更新发布 (实际的)
2018年3月7日
上次提交的符合 QC 标准的更新
2018年3月6日
最后验证
2018年3月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 201579
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
GSK2618960 2 mg/kg的临床试验
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University of Ioannina招聘中
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Hoag Memorial Hospital PresbyterianDa Zen Theranostics Inc邀请报名
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Children's Hospital Medical Center, CincinnatiSobi, Inc.招聘中