Early Markers of Disease and Response to Therapy
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Change in islet-specific exhausted CD8 T cells (%)
研究概览
简要总结
The purpose of this study is to identify early immune markers associated with response to treatment with abatacept in individuals with Type 1 diabetes (T1D). In this open label mechanistic study, participants who were recently diagnosed with T1D (males or females, ages 6-45 and <7months from T1D diagnosis) will be treated with a short-course of abatacept (weekly subcutaneous injections for 3 months). Participants will undergo baseline and repeated mixed meal tolerance testing (MMTT) to assess disease progression and blood samples will be obtained at frequent intervals to measure changes in immune markers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≤ 7 months from type 1 diabetes diagnosis based on ADA criteria
- •> 21 days from type 1 diabetes diagnosis or metabolically stable per study physician assessment
- •Males and females 6-55 years of age, inclusive, at time of screening visit
- •Peak MMTT stimulated C-peptide ≥ 0.2 pmol/ml
- •Females of child-bearing age must be willing to use effective birth control for 1 year (which may include abstinence) from screening visit and undergo regular pregnancy testing
- •Up to date for clinically recommended immunizations prior to screening
- •Willing to forgo live vaccines 3 months prior to the screening visit until three months following last study drug administration
- •Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is < 18 years of age
- •Weight ≥ 20 kg at baseline visit
- •HbA1c ≤ 8.5% at baseline visit
- •Positive for at least 1 diabetes autoantibody (excluding mIAA in those who have received ≥ 2 weeks of exogenous insulin therapy)
排除标准
- •Concurrent or recent (within the past 30 days of screening MMTT (visit -1)) use of non-insulin therapies aimed to control hyperglycemia
- •Females who are pregnant or lactating
- •Immunodeficiency or clinically significant chronic lymphopenia
- •Have an active infection at time of screening or baseline visit
- •Recent exposure, or possible or known active SARS-CoV-2 infection as defined by public health guidelines
- •Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection
- •Active infection with EBV or CMV, defined by real-time PCR
- •History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac disease and stable thyroid disease
- •Require use of other immunosuppressive agents for any other condition
- •Use of medications known to influence glucose tolerance
- •Have any complicating medical or psychological issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. These include pre-existing cardiac disease, COPD, neurological, or clinically significant blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia).
- •Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection.
- •Have a history of malignancies
- •Receipt of live vaccine (MMR, intranasal influenza, varicella, rotatvirus) in 3 months before treatment
研究组 & 干预措施
Abatacept
Abatacept will be given by a subcutaneous (SC) formulation weekly for three months.
干预措施: Abatacept (Drug)
结局指标
主要结局
Change in islet-specific exhausted CD8 T cells (%)
时间窗: 0 to 2 weeks
% of CD8+ T cells (CD8+PD-1+KLRG1+CD57-)
Change in insulin antibody titers (NIDDK units/mL)
时间窗: 0 to 2 weeks
Insulin antibody titers
Change in B-cell transcriptional module (CD19.mod) (composite score)
时间窗: 0 to 2 weeks
CD19 mod is composite score of B cell transcripts.
Change in frequency of B cells within total PBMC (%)
时间窗: 0 to 2 weeks
% of B cells
Change in inflammatory Index by serum transcriptional exposure assay (composite score)
时间窗: 0 to 2 weeks
Inflammatory Index (359). This is an inflammatory index based on transcription of 359 probe sets (I.I.359) calculated by dividing the average signal intensity of the 103 probe sets generally annotated as 'inflammatory' by the average signal intensity of the 256 probe sets generally annotated as 'regulatory'
Change in EOMES CD8 whole blood gene expression signature (composite score)
时间窗: 0 to 2 weeks
Gene transcript score for EOMES module
Change in frequency of TfH within total CD4 T cells (%)
时间窗: 0 to 2 weeks
% of TfH cells within CD4+ T cells
次要结局
未报告次要终点
研究者
Sandra Lord, MD
Clinical Director, Center for Interventional Immunology
Benaroya Research Institute