A Pilot Study on the Effect of Privigen Against Graft Loss: Interventional Study of Kidney Transplant Recipients at Risk for Graft Loss Through Antibody-mediated Rejection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD
研究概览
简要总结
The principal objective of this pilot study is to determine whether the progression of chronic antibody-mediated rejection (ABMR) could be minimized by the post-transplant administration of high dose of Intravenous Immunoglobulins (IVIg).
We test the hypothesis that repetitive IVIg administration reduces or stabilize the progressive loss of transplant function and the evolution to chronic ABMR in stable kidney transplant patients with HLA-DSA developed post-transplantion (de novo HLA-DSA) and concomitant humoral graft injury.
详细描述
The aim of this study is to assess the effect of IVIg associated to conventional immunosuppressive treatment in 15 stable transplant recipients with post-transplant de novo HLA-DSA and histological humoral lesions.
The study will include 2 periods:
- Treatment period,
- Follow-up period. The treatment will start the day of inclusion (M0): Privigen will be given as 2 g/kg for 2 days/month for 6 months (maximum dose: 80 g/day).
Evaluation at the end of treatment will take place on month 6 (M6). Evaluation at the end of follow up will take place on month 12 (M12).
Blood and urine samples will be collected on day of inclusion (M0), before each infusion of Privigen, at M6 and M12 for biological analysis (serum creatinine, glomerular filtration rate, proteinuria).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Deceased donor kidney transplant recipients between 3 and 12 months post transplantation.
- •At least 18 years old.
- •With stable renal function assessed within 30 days before inclusion and with delta GFR (MDRD) lower than 10 ml/min (latest result versus the average of the two previous values).
- •Presence of at least one circulating HLA-DSA class I or II against HLA-A, -B, -DR, -DQ, -DP, -C (MFI ≥ 1000) as assessed by Luminex single antigen technique within 30 days before inclusion.
- •With histological markers of active antibody-mediated injury as defined by the microcirculation inflammation score (g, ptc scores defined by current Banff criteria) on protocol biopsies performed at M3 or M12 post-transplantation, or if required between three and twelve months post transplantation (1 ≤ g+ptc ≤ 3).
- •Able to comply with the study procedures and follow the study instructions.
- •Who have read the information sheet and signed the informed consent form.
排除标准
- •Acute renal dysfunction at the time of enrolment: decrease of GFR higher or equal to 10 ml/min (latest result versus the average of the two previous values), or 20% increase of serum creatinine.
- •Previous episode of ABMR.
- •Previous treatment with plasmapheresis, IVIg, within 2 months prior to inclusion
- •3b. Previous treatment with rituximab, eculizumab or bortezomib within 1 year prior to inclusion
- •Major lesions of active antibody-mediated injury, as defined by Banff criteria, such as g + ptc >3 or chronic transplant glomerulopathy (cg>0).
- •History of cardiac insufficiency (New York Heart Association [NYHA] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, congestive heart failure or severe hypertension.
- •History of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident).
- •Known allergic or other severe reactions to blood products including intolerability to previous IVIg (i.e. severe headache, hypersensitivity, intravascular hemolysis).
- •Subject with a known deficit in IgA, with antibodies against IgA.
- •Known hyperprolinemia.
- •Ongoing HIV, hepatitis C and hepatitis B infection.
- •Any condition (including alcohol, drug or medication abuse) that is likely to interfere with evaluation of the study product or satisfactory conduct of the study.
- •Not able to comply with study procedures and treatment regimen.
- •Pregnant or lactating women or women of childbearing potential without effective method of contraception (oral contraceptive pill, intra-uterine contraceptive device, contraceptive implant or condom).
- •Participation in any other study involving investigational products, concomitantly or within 30 days prior to entry in the study.
研究组 & 干预措施
Human normal immunoglobulin G (IgG > 98 % purity)
All subjects will be treated for 6 months. The treatment will start the day of inclusion (M0).
Privigen will be given as 2 g/kg for 2 days/month. The maximum daily dose authorized will be 80g.
The infusion rates are the recommended rates for Privigen in other indications and are in line with the market authorization for Privigen:
- Infusions should start at a rate of 0.5 mg/kg/min (0.005 mL/kg/min; 0.3 mL/kg/h; 30 mg/kg/h). If well tolerated within 30 min, the rate can be increased in a first step to 1.0 mg/kg/min (0.01 mL/kg/min; 0.6 mL/kg/h; 60 mg/kg/h) for another 30 min.
- If well tolerated, a stepwise increase to a maximum of 8 mg/kg/min (0.08 mL/kg/min; 4.8 mL/kg/h; 480 mg/kg/h) is allowed at the discretion of the investigator.
干预措施: Privigen (Human normal immunoglobulin G (IgG > 98 % purity)) (Drug)
结局指标
主要结局
Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD
时间窗: at months 12
using Modification of Diet in Renal Disease (MDRD) equation at M12
次要结局
- Change of proteinuria from baseline(months 6 and months 12)
- Change of HLA-DSA from baseline(months 6 and months 12)
- Change of Histological characteristics from baseline(at months 6)
- IgG dosage(up to months 6)
- Infectious events reported during the study period(up to months 12)