A Phase II Study to Evaluate the Efficacy of IdeS (IgG Endopeptidase) to Desensitize Transplant Patients With a Positive Crossmatch Test
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 5
- 主要终点
- Number of Patients With Crossmatch Conversion (Positive to Negative)
研究概览
简要总结
The purpose of this study is to evaluate the effectiveness of the study drug IdeS in patients who are on the waiting list for kidney transplant and have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. At study entry, the patients will have an available deceased or live donor with a positive crossmatch test. The study will assess IdeS efficacy and safety in removing Donor Specific Antibodies (DSAs) and thereby convert a positive crossmatch test to negative.
详细描述
The study will assess the IdeS efficacy in creating a negative crossmatch test (XM) in patients who exhibit donor specific antibodies (DSA) and have a positive crossmatch test to their available live or deceased donors. The first 3 patients in this study will receive a kidney from a deceased donor. The study will primarily examine the efficacy of IdeS in creating a negative XM. The first 3 patients will receive one dose of 0.25 mg/kg BW IdeS on study day 0. If it is considered safe and negative crossmatch test is not achieved after the first dose, an additional IdeS infusion can be given within 2 days of the first infusion. The dose schedule may be increased to 0.5 mg/kg BW given once or twice after the first 3 patients have been tested. The decision to escalate the dose will be done after evaluation of safety and efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients on the kidney transplant waitlist who have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. The breadth and strength of sensitization will predict an extremely low likelihood of successful desensitization or kidney paired donation.
- •Patients with a live or deceased donor with a positive crossmatch test.
排除标准
- •Previous treatment with IdeS
- •Previous high dose IVIg treatment (2 g/kg BW) within 28 days prior to IdeS treatment
- •Lactating or pregnant females
- •Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception
- •HIV-positive patients
- •Patients with clinical signs of HBV or HCV infection
- •Patients with active tuberculosis
- •A significantly abnormal general serum screening lab result according to the investigator's judgement. Hgb cannot be < 6.0 g/dL
- •Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD
- •Individuals deemed unable to comply with the protocol
- •Patients with clinical signs of CMV or EBV infection
- •Patients with a history of major thrombotic events, patients with active peripheral vascular disease or patients with proven hypercoagulable conditions
- •Patients should not have received investigational drugs within 4 half-lives (or similar)
- •Known allergy/sensitivity to IdeS infusions
- •Patients who have a live donor and test positive for ImmunoCap anti-IdeS IgE
研究组 & 干预措施
Treatment IdeS
IdeS intravenous infusion
干预措施: IdeS (Drug)
Treatment IdeS
IdeS intravenous infusion
干预措施: Kidney transplantation (Procedure)
结局指标
主要结局
Number of Patients With Crossmatch Conversion (Positive to Negative)
时间窗: Within 24 hours of IdeS dosing
IdeS ability to create a negative crossmatch (XM) test in patients who before treatment exhibit Donor Specific Antibodies (DSAs) and have a positive XM test to their available live or deceased donor kidney. XM was assessed using both FACS and CDC XM tests. FACS XM is a multi-staining procedure where the recipient's serum is used to stain donor cells to identify presence of DSAs in recipient's serum. T- and B-cells are identified using conjugated antibodies against CD3 and CD19. DSAs are identified using a conjugated anti-human antibody. CDC XM evaluates the cytotoxic capacity of the DSAs. The recipient's serum is mixed with donor cells prior to addition of complement. Fluorescent dyes are added and the live/dead cells (%) is scored using a fluorescent microscope. CDC XM amplified with anti-human globulin is not compatible with imlifidase and should not be used. The endpoint was met if at least one XM test was positive pre-dose and the last test within 24 h was negative.
次要结局
- Pharmacokinetics - t1/2(Pre-dose to Day 14 after administration of IdeS.)
- Pharmacokinetics - Vss(Pre-dose to Day 14 after administration of IdeS)
- Pharmacokinetics - Tmax (First Dose)(Pre-dose to Day 14 after administration of IdeS)
- Pharmacokinetics - Tmax (Second Dose)(Pre-dose to Day 14 after administration of IdeS)
- Pharmacokinetics - Cmax (First Dose)(Pre-dose to Day 14 after administration of IdeS.)
- Pharmacokinetics - Vz(Pre-dose to Day 14 after administration of IdeS.)
- Kidney Function After IdeS Treatment Assessed by eGFR(Within 180 days after administration of IdeS)
- Number of Patients With Donor Specific Antibodies With an MFI Value >3000(Within 180 days after administration of IdeS.)
- Time to Create a Negative CDC Crossmatch Test(2h, 6h, 24h after administration of IdeS.)
- Time to Create a Negative FACS Crossmatch Test(2h, 6h, and 24h after administration of IdeS)
- Serum IgG Concentration After Administration of IdeS(Within 180 days after administration of IdeS.)
- Pharmacokinetics - Cmax (Second Dose)(Pre-dose until Day 14 after administration of IdeS)
- Pharmacokinetics - AUC(Pre-dose to Day 14 after administration of IdeS.)
- Pharmacokinetics - CL(Pre-dose to Day 14)