A Phase I/II Trial to Evaluate the Safety and Tolerability of Ides® (IgG Endopeptidase) to Eliminate Donor Specific HLA Antibodies (DSAs) and Prevent Antibody-Mediated Rejection Post-Transplant in Highly-HLA Sensitized Patients.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Number of Participants With Allograft Rejection
研究概览
简要总结
This is a single center phase I/II open label, exploratory study assessing safety and efficacy of IdeS® (Hansa Medical, Lund, Sweden) given immediately prior to kidney transplantation. We hope that IdeS® will help eliminate DSAs in HS patients who are DSA+ and flow cytometry (FCMX) crossmatch + at time of transplant. We plan to enroll a total of 20 patients. Patients will be followed for 6 months post administration of IdeS®.
详细描述
IdeS® is an IgG-degrading enzyme of S.pyogenes that cleaves all four human subclasses of IgG with strict specificity. Alloantibodies are a major deterrent to access to and success of life-saving organ transplants. We hypothesize that the use of IdeS® pre-transplant in HS patients will represent a more robust and complete technique to eliminate DSA from the sera of HS patients. A single dose administration of IdeS® in the pre-operative period to HS patients with positive DSAs and flow cytometry crossmatches will durably eliminate circulating DSAs, allow transplantation to occur without ABMR and, in conjunction with standard desensitization therapy, result in a durable suppression of DSA levels thus eliminating the risk for ABMR.
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
- •End-stage renal disease awaiting transplantation on the UNOS list.
- •No known contraindications for therapy with IVIG10%/Rituximab, plasmapheresis (PLEX) or IdeS®.
- •Age 18-70 years at the time of screening.
- •Calculated PRA (CPRA)> 50% demonstrated on 3 consecutive samples, Patient highly-HLA sensitized and a candidate for DD transplantation after desensitization at CSMC.
- •At transplant, patient must have donor-specific antibody/ crossmatch positive (DSA/CMX+) non-HLA identical donor.
- •Pre-transplant vaccination with Streptococcus pneumoniae and Nisseria meningitides
- •Subject/Parent/Guardian must be able to understand and provide informed consent.
排除标准
- •Positivity for anti-IdeS IgE
- •Use of IVIG 4 weeks prior to planned IdeS® administration
- •Recipients of Extended Criteria Donors (ECD) or Living Donors (LD)
- •Lactating or pregnant females.
- •Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception.
- •HIV-positive subjects.
- •Subjects who test positive for HBV infection [positive HBVsAg, HBVcAb, or HBVeAg/DNA] or HCV infection [positive Anti-HCV (EIA) and confirmatory HCV RIBA].
- •Subjects with active TB.
- •Subjects with selective IgA deficiency, those who have known anti-IgA antibodies, and those with a history of anaphylaxis or severe systemic responses to any part of the clinical trial material.
- •Subjects who have received or for whom multiple organ transplants are planned.
- •Recent recipients of any licensed or investigational live attenuated vaccine(s) within two months of the screening visit (including but not limited to any of the following:
- •Adenovirus [Adenovirus vaccine live oral type 7]
- •Varicella [Varivax]
- •Hepatitis A [VAQTA]
- •Rotavirus [Rotashield]
- •Yellow fever [Y-F-Vax]
- •Measles and mumps [Measles and mumps virus vaccine live]
- •Measles, mumps, and rubella vaccine [M-M-R-II]
- •Sabin oral polio vaccine
- •Rabies vaccines [IMOVAX Rabies I.D., RabAvert])
- •A significantly abnormal general serum screening lab result defined as a WBC < 3.0 X 103/ml, a Hgb < 8.0 g/dL, a platelet count < 100 X 103/ml, , an SGOT > 3X upper limit .
- •Individuals deemed unable to comply with the protocol.
- •Subjects with active CMV or EBV infection as defined by CMV-specific serology (IgG or IgM) and confirmed by quantitative PCR with or without a compatible illness.
- •Subjects with a known history of previous myocardial infarction within one year of screening.
- •Subjects with a history of clinically significant thrombotic episodes, and subjects with active peripheral vascular disease.
- •Subjects with Protein C and Protein S deficiency
- •Use of investigational agents within 4 weeks of participation.
- •Known allergy/sensitivity to IdeS® infusions
研究组 & 干预措施
IdeS®
Twenty patients will receive 0.24mg/kg (n=20)
干预措施: IdeS® (Imlifidase) (Drug)
结局指标
主要结局
Number of Participants With Allograft Rejection
时间窗: 6 months
Number of participants with allograft rejection will be assessed at 6 month post transplant renal biopsy.
次要结局
- Proteinuria(6 months post transplant)
- Number of Participants With Donor Specific Antibodies (DSA) Post-transplant(6 months post transplant)
- eGFR(6 months post transplant)
研究者
Stanley Jordan, MD
MD
Cedars-Sinai Medical Center