Steroid and Tacrolimus Avoidance Using NULOJIX® (Belatacept) in Renal Transplantation (CTOT-16)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 71
- 试验地点
- 3
- 主要终点
- Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant
研究概览
简要总结
The primary objective is to evaluate a NULOJIX® (belatacept) based regimens as a means of improving long-term graft function without increasing the risks of immunologic graft injury by avoiding both calcineurin inhibitors (CNIs) and corticosteroids.
详细描述
Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. Transplant recipients have to take anti-rejection medications to prevent their immune system (the body's natural defense system against illness) from rejecting their new kidney. Most patients who receive a kidney transplant must take these anti-rejection medications for the rest of their lives, or for as long as the kidney continues to work.
The purpose of this study is to determine if NULOJIX® (belatacept), will minimize serious long term side effects seen with anti-rejection medications while still protecting the transplanted kidney from damage. The researchers also want to learn more about the safety of this treatment and the long term health of the transplanted kidney.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female, 18-65 years of age at the time of enrollment;
- •Ability to understand and provide written informed consent;
- •Candidate for primary renal allograft from either living or deceased donor;
- •No known contraindications to study therapy using NULOJIX® (belatacept);
- •Female participants of childbearing potential must have a negative pregnancy test upon study entry;
- •Participants with reproductive potential must agree to use an appropriate method(s) of birth control as outlined in the CellCept® , Myfortic® or generic package labeling during participation in the study and for 4 months following completion of the study;
- •No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
- •Negative crossmatch or Panel Reactive Antibodies (PRA) of 0% on historic and current sera, as determined by each participating study center;
- •A documented negative tuberculosis (TB) test within the 6 months prior to transplant. If documentation is not present at the time of transplantation, and the subject does not have any risk factors for TB, a TB-specific interferon gamma release assay (IGRA) may be performed.
排除标准
- •Need for multi-organ transplant;
- •Recipient of previous organ transplant;
- •Epstein-Barr Virus (EBV) seronegative (or unknown) recipients;
- •Active infection including hepatitis B, hepatitis C, or human Immunodeficiency Virus (HIV);
- •Individuals who have required treatment with prednisone or other immunosuppressive drugs within 1 year prior to transplant;
- •Individuals undergoing transplant using organs from extended criteria donor (ECD) or donation after cardiac death (DCD) donors;
- •Histocompatibility antigen (HLA) identical living donors;
- •Individuals at significant risk of early recurrence of the primary renal disease including focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN) type 2 or any other disease that in the opinion of the investigator is at increased likelihood of recurrence and which may result in rapid decline in renal function;
- •Known history of thrombotic events or risk factors, including any of the following:
- •Factor V Leiden, elevated homocysteine, positive lupus anticoagulant, elevated anticardiolipin antibody, heparin-induced thrombocytopenia,
- •A family history of a heritable thrombotic condition,
- •Recurrent deep vein thrombosis (DVT) or pulmonary emboli (PE),
- •Unexplained stillborn infant or recurrent spontaneous abortion or other congenital or acquired thrombotic disorder.
- •At the discretion of the investigator, a history of thrombosis of a dialysis access graft, fistula, or indwelling catheter/device may not be considered an exclusion criterion.
- •Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;
- •Use of investigational drugs within 4 weeks of enrollment;
- •Known hypersensitivity to mycophenolate mofetil (MMF)or any of the drug's components;
- •Administration of live attenuated vaccine(s) within 8 weeks of enrollment;
- •Blood type A2 and A2B donors into blood type B recipients.
研究组 & 干预措施
Thymoglobulin®+tacrolimus+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)
干预措施: Anti-thymocyte Globulin (Rabbit) (Biological)
Thymoglobulin®+tacrolimus+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)
干预措施: methylprednisolone (Drug)
Thymoglobulin®+tacrolimus+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)
干预措施: mycophenolate mofetil (Drug)
Thymoglobulin®+tacrolimus+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)
干预措施: tacrolimus (Drug)
Thymoglobulin®+belatacept+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF)
干预措施: Anti-thymocyte Globulin (Rabbit) (Biological)
Thymoglobulin®+belatacept+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF)
干预措施: belatacept (Biological)
Thymoglobulin®+belatacept+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF)
干预措施: methylprednisolone (Drug)
Thymoglobulin®+belatacept+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF)
干预措施: mycophenolate mofetil (Drug)
Basiliximab+20 weeks of tacrolimus+MMF + belatacept
Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent.
Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.
干预措施: belatacept (Biological)
Basiliximab+20 weeks of tacrolimus+MMF + belatacept
Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent.
Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.
干预措施: methylprednisolone (Drug)
Basiliximab+20 weeks of tacrolimus+MMF + belatacept
Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent.
Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.
干预措施: basiliximab (Biological)
Basiliximab+20 weeks of tacrolimus+MMF + belatacept
Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent.
Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.
干预措施: mycophenolate mofetil (Drug)
Basiliximab+20 weeks of tacrolimus+MMF + belatacept
Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent.
Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.
干预措施: tacrolimus (Drug)
结局指标
主要结局
Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant
时间窗: Week 52
eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): * A score of ≥90 means kidney function is normal. * A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. * Scores between 30 and 59 indicates moderately reduced kidney function. * Scores between 15 and 29 indicate severely reduced kidney function. * Scores below 15 indicate very severe or end stage kidney failure.
次要结局
- Count of Participants With Biopsy Proven Acute Rejection By Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant(Week 52)
- Count of Participants by CKD Stage at Wk 52(Week 52)
- Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant(Week 52)
- Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant(Week 52)
- The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant(Day 28 through Week 52 Post-Transplant)
- Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants With Acute Cellular Rejection Grade ≥ IA Defined by Banff 2007 Criteria By Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants by Severity of First Acute Cellular Rejection by Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants With Antibody Mediated Rejection by Wk 52 Post-Transplant(Transplantation through Week 52)
- Type of Rejection Classified by Pathologist - For Cause Kidney Biopsies(Transplantation through Week 52)
- Type of Treatment for Detected Graft Rejection(Transplantation through Week 52)
- Count of Participants With De Novo Anti-Donor Histocompatibility Antigen (HLA) Antibodies at Wk 52 Post-Transplant(Week 52)
- Count of Participants With Either New Onset Diabetes After Transplant (NODAT) or Impaired Fasting Glucose (IFG) at Week 52 Post-Transplant -Based on Criteria Specified by the ADA and WHO(Transplantation through Week 52)
- Count of Participants With Treated Diabetes Between Day 14 and Wk 52 Post-Transplant(Day 14 through week 52)
- Hemoglobin A1c (HbA1c) Measurements Over Time(Baseline (Pre-Transplant) and Days 28 and -84, and Weeks 28, -36, and -52 Post-Transplant)
- Standardized Blood Pressure Measurement at Wk 52 Post-Transplant(Week 52)
- Count of Participants With Use of Anti-hypertensive Medication at Wk 52 Post-Transplant(Week 52)
- Fasting Lipid Profile at Baseline (Pre-Transplant)(Baseline)
- Fasting Lipid Profile at Wk 28 Post-Transplant(Week 28)
- Fasting Lipid Profile at Wk 52 Post-Transplant(Week 52)
- Count of Participants With Use of Lipid Lowering Medications at Baseline and Wk 28 and Wk 52 Post-Transplant(Baseline (Pre-Transplant), Week 28, and Week 52)
- Total Daily Prescribed Pill Count(Day 28, Day 84, Week 28, Week 36, and Week 52)
- Count of Participant Deaths or Graft Loss by Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants With Graft Rejection by Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants Experiencing ≥ 1 Adverse Event (AEs) or Serious Adverse Events (SAEs) by Wk 52(Enrollment through Week 52)
- Count of Participants With Infections Requiring Hospitalization or Systemic Therapy by Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia (Local Center Monitoring) as Adverse Events by Wk 52 Post-Transplant(Transplantation through Week 52)
- Count of Participants With Epstein-Barr Virus (EBV) Infection as Reported on the Case Report Form as Adverse Events(Transplantation through Week 52)
- Count of Participants With Fever > 39 Degrees Celsius and Blood Pressure < 90 mmHg Within 24 Hours of Onset of Transplant Procedure(Within 24 Hours of transplant procedure)