A Two Part, Phase 1/2, Safety, PK and PD Study of TOL101, an Anti-TCR Monoclonal Antibody for Prophylaxis of Acute Organ Rejection in Patients Receiving Renal Transplantation
试验速览
- 阶段
- 1 期
- 入组人数
- 85
- 试验地点
- 12
- 主要终点
- To assess the safety and tolerability of ascending doses of TOL101 and the effectiveness of TOL101 to target and downregulate T cells in patients undergoing first renal transplantation
研究概览
简要总结
Induction therapy with antibodies is administered during transplant surgery and for a short period of time following transplant surgery in an effort to render the immune system less able to mount an initial rejection response. In general, induction therapy is associated with better outcomes compared to the absence of induction therapy. However, currently used induction agents, some of which are not labeled or indicated for induction therapy in transplantation, have drawbacks related to long-term immune system suppression increasing susceptibility to opportunistic infections or malignancies, and other immune-mediated side effects.
An unmet medical need exists for a more specific approach to prevent acute organ rejection, without unnecessarily exposing the patient to non-specific or open-ended immune suppression, which may exacerbate the risks of infections and malignancies. TOL101 is a novel antibody that targets a very specific immune cell type that is critical in the acute organ rejection response. In this two-part study, TOL101 will be evaluated for the prophylaxis of acute organ rejection when used as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus in first time kidney transplant recipients.
This study will test the hypothesis that a more specific approach (with TOL101) to prevention of acute organ rejection may provide similar or better efficacy than the currently used induction antibodies (such as Anti-Thymocyte Globulin or Thymoglobulin) while carrying fewer risks in terms of opportunistic infections, malignancies and adverse effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient of a primary renal transplant from a living or standard criteria cadaveric donor
- •Male or female 18-60 years of age
- •Recipient with a PRA < 20%
排除标准
- •Previous solid organ transplant
- •Recipient of HLA-identical kidney allograft transplant
- •Recipient of an ABO incompatible donor kidney
- •Known HIV infection or other major infection
- •History of malignancy within 3 years (excluding treated basal cell or squamous cell carcinoma of the skin) prior to enrollment
- •History of tuberculosis
- •Recipient with cardiovascular disease
- •Treatment with immunosuppressive medications within 1 month prior to enrollment
- •Known or suspected allergy to mice
- •Pregnant or lactating
- •Unable or unwilling to participate in all required study activities for the duration of the study (6 months)
研究组 & 干预措施
Anti-Thymocyte Globulin
Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Anti-Thymocyte Globulin (Drug)
Anti-Thymocyte Globulin
Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Steroids (Drug)
Anti-Thymocyte Globulin
Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Tacrolimus (Drug)
Anti-Thymocyte Globulin
Anti-Thymocyte Globulin induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Mycophenolate mofetil (MMF) (Drug)
TOL101 (Dose A)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: TOL101 (Drug)
TOL101 (Dose A)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Steroids (Drug)
TOL101 (Dose A)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Tacrolimus (Drug)
TOL101 (Dose A)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Mycophenolate mofetil (MMF) (Drug)
TOL101 (Dose B)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: TOL101 (Drug)
TOL101 (Dose B)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Steroids (Drug)
TOL101 (Dose B)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Tacrolimus (Drug)
TOL101 (Dose B)
TOL101 induction as part of an immunosuppressive regimen that includes steroids, MMF, and tacrolimus.
干预措施: Mycophenolate mofetil (MMF) (Drug)
结局指标
主要结局
To assess the safety and tolerability of ascending doses of TOL101 and the effectiveness of TOL101 to target and downregulate T cells in patients undergoing first renal transplantation
时间窗: 6 months
The following safety parameters will be monitored: Adverse events, standard laboratory safety evaluations (hematology and serum chemistries), symptom constellation indicating cytokine release syndrome, serum concentrations of cytokines and nitric oxide, malignancies, CMV viremia, BKV viremia, EBV viremia and other infections
次要结局
- The effects of ascending doses of TOL101 on CD3+ T lymphocyte numbers and other immune cell subsets(14 days post-transplant (Part A); 6 months (Part B))
- Biopsy-proven acute organ rejection(6 months)
- Patient survival(6 months)
- Graft survival(6 months)
- Renal function by measured GFR at 6 months post-transplant and urine protein to creatinine ratio at 3 and 6 months post-transplant(6 months)
- The presence of Donor Specific Antibody at 3 months (Part B only) and 6 months post-transplant(6 months)
- The pharmacokinetic (PK) profile of TOL101 in renal transplant recipients and the exposure-response (PK parameter to CD3+ T lymphocyte numbers) relationship over time(14 days post-transplant)
- Delayed graft function(first 7 days post-transplant)
- Immunogenicity of TOL101 by measurement of anti-TOL101 antibodies(at 14 and 28 days post-transplant)