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
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Number of subjects with abnormal clinical chemistry values: Part 1
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a randomized, double blind (sponsor unblind) study and masking will be performed.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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.
排除标准
- •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
研究组 & 干预措施
Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
干预措施: GSK2618960 2 mg/kg (Drug)
Part I & II: GSK2618960 2 milligram per kilogram (mg/kg)
GSK2618960 2mg/kg will be administered intravenously (IV) with Methotrexate (MTX)
干预措施: Methotrexate (Drug)
Part II: Placebo
Placebo will be administered IV with MTX
干预措施: Placebo (Drug)
Part II: Placebo
Placebo will be administered IV with MTX
干预措施: Methotrexate (Drug)
结局指标
主要结局
Number of subjects with abnormal clinical chemistry values: Part 1
时间窗: Up to Week 29
Samples for clinical chemistry tests will be collected as a measure of safety
Number of subjects with abnormal hematology values: Part 1
时间窗: Up to Week 29
Samples for clinical hematology tests will be collected as a measure of safety
Number of subjects with abnormal urine analysis values: Part 1
时间窗: Up to Week 29
Samples for Urine analysis tests will be collected as a measure of safety
Number of subjects with abnormal findings of pulse rate: Part 1
时间窗: Up to Week 29
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with abnormal clinical chemistry values: Part 2
时间窗: Up to Week 35
Samples for clinical chemistry tests will be collected as a measure of safety
Number of subjects with abnormal findings of body temperature: Part 1
时间窗: Up to Week 29
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with abnormal findings of blood pressure: Part 1
时间窗: Up to Week 29
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with abnormal findings of respiratory rate: Part 1
时间窗: Up to Week 29
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with abnormal urine analysis values: Part 2
时间窗: Up to Week 35
Samples for Urine analysis tests will be collected as a measure of safety
Number of subjects with abnormal findings of body temperature: Part 2
时间窗: Up to Week 35
Body temperature will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with Adverse Events (AEs): Part 1
时间窗: Up to Week 29
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.
Number of subjects with AEs: Part 2
时间窗: Up to Week 35
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.
Number of subjects with abnormal findings of blood pressure: Part 2
时间窗: Up to Week 35
SBP and DBP will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with abnormal findings of pulse rate: Part 2
时间窗: Up to Week 35
Pulse rate will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with abnormal findings of respiratory rate: Part 2
时间窗: Up to Week 35
Respiratory rate will be measured in a semi-supine position after at least a 5-minute rest.
Number of subjects with abnormal ECG findings: Part 2
时间窗: Up to Week 35
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Number of subjects with abnormal Electrocardiogram (ECG) findings: Part 1
时间窗: Up to Week 29
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine
Number of subjects with abnormal hematology values: Part 2
时间窗: Up to Week 35
Samples for clinical hematology tests will be collected as a measure of safety
次要结局
- Plasma concentration of GSK2618960: Part 1(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)
- Minimum observed plasma concentration (Cmin) of GSK2618960: Part 1(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)
- Cmax of GSK2618960: Part 2(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)
- Change from Baseline in Focus score: Part 2(Up to Day 29)
- Maximum observed plasma concentration (Cmax) of GSK2618960: Part 1(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)
- Number of incidences of Anti-drug antibody (ADA) formation: Part 1(Up to Week 29)
- Time to onset of ADA: Part 2(Up to Week 35)
- Percentage inhibition of Signal transducer and activator of transcription 5 (STAT 5) phosphorylation in T cells: Part 2(Up to Week 35)
- Area under the curve (AUC) of GSK2618960: Part 1(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)
- Time to onset of ADA: Part 1(Up to Week 29)
- Number of incidences of ADA formation: Part 2(Up to Week 35)
- Number of incidences of ADA neutralization: Part 2(Up to Week 35)
- Number of titres of ADA: Part 1(Up to Week 29)
- Number of incidences of ADA neutralization: Part 1(Up to Week 29)
- Plasma concentration of GSK2618960 : Part 2(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)
- AUC of GSK2618960: Part 2(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)
- Number of titres of ADA: Part 2(Up to Week 35)
- Receptor occupancy (RO) on circulating T cells: Part 2(Up to Week 35)
- Cmin of GSK2618960: Part 2(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)