A Multicenter, Prospective, One-arm Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- The change of donor specific antibody
研究概览
简要总结
Renal transplantation is the best choice for the treatment of end-stage renal disease, but the long-term survival of the graft is still remains a challenge. Chronic antibody-mediated rejection (AMR) is the main factor affecting the long-term survival of the graft. There is still no effective treatment for chronic antibody-mediated rejection, even in the active phase (CaAMR). In recent years, new therapeutic drugs based on the generation of DSA and the mechanism of AMR, including protease inhibitor bortezomi, CD20 monoclonal antibody, C5 monoclonal antibody and IL-6 antibody, have not been able to effectively eliminate and inhibit the generation of DSA, nor have they been proved to have a definite effect on AMR.
CD38 is a type II transmembrane protein that is highly expressed on plasma cells and NK cells, which are considered to play a key role in the occurrence and development of AMR. Recently, a few cases have reported that CD38 monoclonal antibody combined plasma exchange and/or IVIG may be an effective strategy for the prevention and treatment of AMR, but the effectiveness and safety of daratumumab monotherapy on CaAMR were unknown. This is a multicenter, prospective, single arm clinical study. The study will enroll 15 renal transplant recipients with positive DSA and CaAMR confirmed by biopsy after renal transplantation. According to inclusion and exclusion criteria patients will be screened to participate in the trial.
详细描述
After successful enrollment, the patient will receive daratumumab of 16mg/kg once every two weeks (0-22 weeks) for a total of 12 times, and continue to receive triple immunosuppressive therapy with prednisone, mycophenolic acid, tacrolimus (target valley concentration of 5-7ng/ml) or cyclosporine (target valley concentration of 100-200ng/ml). Peripheral blood samples were collected from 0 to 24 weeks (weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24) for routine blood tests, liver and kidney function electrolytes, tacrolimus or cyclosporine trough concentrations, HLA antibody quantification (weeks 0, 4, 8, 12, 16, 20, and 24), infection indicators (weeks 0, 8, and 24), immune status assessments (weeks 0, 4, 8, 12, 16, 20, and 24), and biopsy of transplanted kidneys was performed at 24 weeks to assess pathological changes.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary signing of written informed consent
- •Age ≥ 18 years old
- •≥ 180 days after living donor kidney or DD donor kidney transplantation
- •EGFR ≥ 30mL/min/1.73 m2 (CKD-EPI formula)
- •Pre stored and/or newborn DSA (HLA antibody)
排除标准
- •Patients participating in another clinical trial
- •Age less than 18 years old
- •Female subjects are pregnant or breastfeeding, or do not receive appropriate contraceptive measures
- •ABO incompatibility transplantation
- •Kidney transplantation biopsy combined with one of the following results:
- •A. T-cell mediated rejection B. New or recurrent severe thrombotic microangiopathy C. Polyomavirus nephropathy
- •Receive anti acute rejection treatment within 3 months before screening
- •Have been treated with other immunomodulatory monoclonal/polyclonal antibodies (such as CD20 antibody, bortezomib, C5 monoclonal antibody, IL-6/IL-6R antibody) within 3 months
- •Total bilirubin>2 times the upper normal limit, alanine aminotransferase and aspartate aminotransferase>2.5 times the upper normal limit
- •Hemoglobin<8 g/dL
- •Thrombocytopenia: Platelets<100 × 109/L
- •Leukopenia: White blood cells<3 × 109/L, neutropenia: neutrophils<1.5 × 109/L
- •Hypogammaglobulinemia: Serum IgG<400 mg/dL
- •Eliminate active viral, bacterial, or fungal infections
- •Excluding Active Malignant Diseases with Intensive Immunosuppressive Therapy
- •Latent or active tuberculosis
- •Inoculate live vaccine within 6 weeks after screening
- •History of alcohol or illicit drug abuse
- •Serious medical or mental illness that may affect participation in the study
- •Active hepatitis B virus infection
研究组 & 干预措施
Patient with CaAMR
This is a multicenter, prospective, single arm clinical study. The study will enroll 15 renal transplant recipients with positive DSA and CaAMR confirmed by biopsy after renal transplantation. According to inclusion and exclusion criteria patients will be screened to participate in the trial.
干预措施: Daratumumab (Drug)
结局指标
主要结局
The change of donor specific antibody
时间窗: 6 months
Donor specific antibody changed 30% based on luminex HLA testing
次要结局
- The change of serum creatinine(6 months)
- The change of BANFF score(6 months)
- Incidence of treatment-related adverse events(6 months)
- The change of NK cell count in PBMC(6 months)