A Three-part, Partially Open Label and Double-blind, Randomized Study to Assess the Pharmacodynamic Effects, Safety, Tolerability and Preliminary Efficacy of VAY736 in Patients With Primary Sjögren's Syndrome Using [Zr-89]-Rituximab PET/CT
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Part 3: To compare the effect of two different VAY736 s.c. dose regimes on salivary gland-infiltrating B cells in pSS patients, using [Zr-89]-rituximab PET/CT imaging
研究概览
简要总结
This study consists of three consecutive parts. Part 1 in primary Sjögren's syndrome (pSS) patients (n=2-6) and Part 2 in healthy voluteers (n=3) are feasibility studies to assess if the selected [Zr-89]-rituximab PET/CT method is a valid method to assess B cells in salivary glands of pSS patients. In Part 1 and Part 2 no IMP will be applied to the subjects. In Part 3, pSS patients (n=12) will receive the IMP, VAY736. Posted information will be focused on Part 3.
The overarching purpose of this study is to test a new drug (VAY736) for the treatment of pSS. In pSS, the salivary glands (the glands that produce saliva) and other organs are affected by inflammation. A certain type of white blood cells called B cells prominently infiltrate the salivary glands in pSS, whereas they are not present in healthy salivary glands. Scientific evidence suggests that B cells may be involved in the disease process in pSS and that eliminating B cells may benefit patients with pSS. This study will test a new imaging method and a new treatment for pSS. Both the imaging method and the treatment are specific for B cells.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fullfilled consensus criteria for primary Sjögren's syndrome
- •Patients must have elevated serum levels for some Sögren Syndorme specific parameters such as antinuclear antibodies (ANA), rheumatoid factor (RF) etc.
排除标准
- •Patients that are suffering from Secondary Sjögren's syndrome.
- •Patients previously treated with monoclonal antibody treatments such as rituximab, infliximab, adalimumab, etc.
- •Inclusion criteria:
- •healthy male and female people 18-75 years of age
- •Exclusion criteria:
- •Use of other investigational drugs at the time of enrollment
- •Exposure to a sizeable degree of radiation (≥ 5 mSv) in an investigational research study in the past year prior to this study
研究组 & 干预措施
VAY736 lower dose
12 evaluable patients will be enrolled and randomized (at a ratio of 1:1) to receive either a lower dose or a higher dose of the study drug (VAY736)
干预措施: VAY736 lower dose (Drug)
VA736 higher dose
12 evaluable patients will be enrolled and randomized (at a ratio of 1:1) to receive either a lower dose or a higher dose of the study drug (VAY736)
干预措施: VAY736 higher dose (Drug)
结局指标
主要结局
Part 3: To compare the effect of two different VAY736 s.c. dose regimes on salivary gland-infiltrating B cells in pSS patients, using [Zr-89]-rituximab PET/CT imaging
时间窗: Part 3: 12 weeks
Part 3: PET/CT imaging of pSS tissues on optimal time point after i.v. injection with \[Zr-89\]-rituximab, at baseline and 12 weeks after the start of VAY736 treatment
Part 1: To determine the feasibility of measuring major salivary gland infiltrating B cells in pSS patients using [Zr- 89]rituximab PET/CT imaging
时间窗: Part 1: 4 weeks
Part 1: PET/CT imaging of pSS major salivary gland 3, 6 and 9 days after i.v. injection with \[Zr- 89\]rituximab
Part 2: To define the normal range of PET/CT imaging values for major salivary gland tissue, cervical lymph nodes and spleen in healthy volunteers with [Zr-89]-rituximab
时间窗: Part 2: 4 weeks
Part 2: PET/CT imaging of healthy volunteers' major salivary gland, cervical lymph nodes and spleen on optimal time point after i.v. injection with \[Zr-89\]-rituximab (e.g. 3 days after injection)
次要结局
- Safety of multiple s.c. dosing of VAY736 in pSS patients as measured by safety assessments(12 weeks)
- To asses the pharmacokinetiks of VAY736 in pSS patients(12 weeks)
- To assess the pharmacokinetiks of VAY736 in pSS patients(12 weeks)
- Assess the pharmacodynamic effect of VAY736 on circulating CD19+ B-cells in pSS(12 weeks)
- Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS(12 weeks)
- To evaluate the effect of two different VAY736 dose levels (s.c. q4w) on pSS disease activity(12 weeks)
- To evaluate the effect of on self-reported outcomes in pSS patients(12 weeks)
- To evaluate the change in the physician global assessment of patients's overall disease activity(12 weeks)
- To evaluate the change in the patients global assessment of their disease activity(12 weeks)
- To assess the immunogenicity of VAY736(12 weeks)
- To assess the immunogenicity of a micodose of rituximab(25 weeks)