An Exploratory/Proof of Concept Investigation of the Safety and Pharmacodynamics of LY2127399 in HLA-Presensitized Patients With End-Stage Renal Disease Awaiting Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Change From Baseline in PRA
研究概览
简要总结
The purpose of this trial is to explore the effect of LY2127399 on those antibodies that are a barrier to kidney transplant. Transplantation is currently the definitive treatment for End-Stage Renal Disease (ESRD), providing prolonged survival and improved quality of life.
详细描述
In this study, LY2127399 will be tested as a potential treatment to reduce the blood proteins in some participants with ESRD. These proteins are called alloantibodies and are made by the body to react with other proteins on cells of transplanted organs called human leukocyte antigen (HLA) proteins. When a participant has these antibodies, they are referred to as HLA-presensitized. Often the presence of these antibodies, categorized by a method called the panel reactive antibody (PRA), can make a person ineligible to receive a transplant or experience very long wait times on the kidney transplant waiting list. Therefore the need to reduce the antibodies is significant for the successful treatment of ESRD. This study will treat ESRD participants for 6 months with LY2127399 and measure PRA levels for a total of 18 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have ESRD and are awaiting kidney transplant
- •Have a stable PRA score >50%
排除标准
- •Have had a tonsillectomy
- •Have a semi-permanent/tunneled catheter
- •Have had intravenous immunoglobulin (IVIg) in the past 6 months
- •Have had plasmapheresis in the past 6 months
- •Uncontrolled hypertension
- •Presence of clinically significant cardiac disease in the past 6 months
- •Malignancy in the past 5 years, with the exception of cervical, basal cell and squamous epithelial cell cancers
- •Have active or recent infection including herpes zoster or herpes simplex in the last 30 days
- •Have evidence or suspicion of active Tuberculosis (TB)
- •Have had major surgery in the past 2 months
- •Have had a serious infection with recovery in the past 3 months
- •Have Hepatitis B or C or have Human Immunodeficiency Virus (HIV)
研究组 & 干预措施
LY2127399
干预措施: LY2127399 (Drug)
结局指标
主要结局
Change From Baseline in PRA
时间窗: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
The PRA value is calculated and expressed as a percentage, which can range from 0 % to 100%. The value represents a summation of the total HLA antibody burden that the participant has and how frequently those HLA antigens appear in organ donor population. A calculated PRA of 20% means the participant has antibodies that represent an antigen frequency that exists in approximately 20% of the population.
Change From Baseline in Arcsine Transformed PRA Scores
时间窗: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
The PRA value is calculated and expressed as a percentage, which can range from 0% to 100%. The value represents a summation of the total HLA antibody burden that the participant has and how frequently those HLA antigens appear in organ donor population. A calculated PRA of 20% means the participant has antibodies that represent an antigen frequency that exists in approximately 20% of the population. PRA scores were transformed using the arcsine function, which enables a skewed distribution of data typically expressed as proportions to achieve properties closer to a normal distribution. The range of possible arcsine transformed PRA scores is 0 (when PRA = 0) to approximately 1.57 (when PRA =100). Higher scores indicate the participant has antibodies against HLA antigens that appear frequently in the organ donor population.
Number of Participants With a Change From Baseline Positive to Post-Baseline Negative in the Summation of Top 10 Highest Antibody Levels (Class I and Class II Single Antigen Reactivity Reported Separately) During Treatment and Follow-Up
时间窗: Baseline through Weeks 24, 52 and 76
次要结局
- Change From Baseline in Serum Immunoglobulin Levels(Baseline, Weeks 8, 16, 24, 36 and 52)
- Percent Change From Baseline at Week 1 and Week 24 in Relative Percent of Lymphocytes for B Cell Populations in the Tonsil(Baseline, Weeks 1 and 24)
- Percent Change From Baseline in Relative Percent of Lymphocytes for B Cell Populations in Peripheral Blood(Baseline, Weeks1, 4, 8, 16, 24, 36, 52, 64 and 76)
- Percent Change From Baseline in Absolute Counts of B Cell Populations in Peripheral Blood(Baseline, Weeks1, 4, 8, 16, 24, 36 and 52)
- Population Pharmacokinetics (PK): Constant Clearance(Baseline through Week 24)