Optimization of NULOJIX® (Belatacept) Usage as a Means of Avoiding CNI and Steroids in Renal Transplantation (CTOT-10)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 3
- 主要终点
- Mean Glomerular Filtration Rate (GFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52
研究概览
简要总结
The purpose of this study was to assess whether a new drug, Nulojix® (belatacept), would minimize serious long term side effects associated with anti-rejection medications while still protecting the new kidney from damage. The researchers also wanted to learn more about the safety of this treatment and long term health of the transplanted kidney.
详细描述
Dialysis or kidney transplant are the two ways to treat kidney failure. 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 undergo a kidney transplant must take these anti-rejection medications for the rest of their lives. Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but don't damage the 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 a 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;
- •Female and male participants with reproductive potential must agree to use FDA approved methods of birth control during participation in the study and for 4 months following completion of the study;
- •Flow-based PRA within last 12 months (in absence of a sensitizing event) of < 30% as determined by each participating study center. If the subject experienced a sensitizing event after the PRA test date, then the PRA must be repeated and confirmed <30%;
- •Negative crossmatch or a PRA of 0% on historic and admission sera as determined by each participating study center.
- •A documented negative TB test within the 12 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;
- •EBV sero-negative (or unknown) recipients;
- •Active infection including hepatitis B, hepatitis C, or 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;
- •HLA identical living donors;
- •Individuals at significant risk of early recurrence of the primary renal disease including FSGS and 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;
- •Individuals previously treated with NULOJIX® (belatacept);
- •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.
研究组 & 干预措施
Tac maintenance
Group 1 Study Therapy Regimen:Induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); long-term Prograf® (tacrolimus), or equivalent ; CellCept® (mycophenolate mofetil- MMF), or equivalent , and 4 day course of MEDROL® (methylprednisolone)
干预措施: Alemtuzumab (Drug)
Tac maintenance
Group 1 Study Therapy Regimen:Induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); long-term Prograf® (tacrolimus), or equivalent ; CellCept® (mycophenolate mofetil- MMF), or equivalent , and 4 day course of MEDROL® (methylprednisolone)
干预措施: MMF (Drug)
Tac maintenance
Group 1 Study Therapy Regimen:Induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); long-term Prograf® (tacrolimus), or equivalent ; CellCept® (mycophenolate mofetil- MMF), or equivalent , and 4 day course of MEDROL® (methylprednisolone)
干预措施: tacrolimus (Drug)
Tac maintenance
Group 1 Study Therapy Regimen:Induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); long-term Prograf® (tacrolimus), or equivalent ; CellCept® (mycophenolate mofetil- MMF), or equivalent , and 4 day course of MEDROL® (methylprednisolone)
干预措施: methylprednisolone (Drug)
Belatacept maintenance
Group 2 Study Therapy Regimen: Induction with alemtuzumab and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); Nulojix® (belatacept); CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL®(Methylprednisolone)
干预措施: Alemtuzumab (Drug)
Belatacept maintenance
Group 2 Study Therapy Regimen: Induction with alemtuzumab and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); Nulojix® (belatacept); CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL®(Methylprednisolone)
干预措施: MMF (Drug)
Belatacept maintenance
Group 2 Study Therapy Regimen: Induction with alemtuzumab and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); Nulojix® (belatacept); CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL®(Methylprednisolone)
干预措施: Belatacept (Biological)
Belatacept maintenance
Group 2 Study Therapy Regimen: Induction with alemtuzumab and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Campath® (alemtuzumab); Nulojix® (belatacept); CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL®(Methylprednisolone)
干预措施: methylprednisolone (Drug)
Basiliximab induction/Short-term Tac
Short term = 3 months
Group 3 Study Therapy Regimen: Induction with 2 doses of basiliximab and tacrolimus for 84 days and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Simulect® (basiliximab); Nulojix® (belatacept); short-term course of Prograf® (tacrolimus), or equivalent; CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL® (methylprednisolone)
干预措施: MMF (Drug)
Basiliximab induction/Short-term Tac
Short term = 3 months
Group 3 Study Therapy Regimen: Induction with 2 doses of basiliximab and tacrolimus for 84 days and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Simulect® (basiliximab); Nulojix® (belatacept); short-term course of Prograf® (tacrolimus), or equivalent; CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL® (methylprednisolone)
干预措施: Basiliximab (Biological)
Basiliximab induction/Short-term Tac
Short term = 3 months
Group 3 Study Therapy Regimen: Induction with 2 doses of basiliximab and tacrolimus for 84 days and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Simulect® (basiliximab); Nulojix® (belatacept); short-term course of Prograf® (tacrolimus), or equivalent; CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL® (methylprednisolone)
干预措施: Short-term Tac (Drug)
Basiliximab induction/Short-term Tac
Short term = 3 months
Group 3 Study Therapy Regimen: Induction with 2 doses of basiliximab and tacrolimus for 84 days and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Simulect® (basiliximab); Nulojix® (belatacept); short-term course of Prograf® (tacrolimus), or equivalent; CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL® (methylprednisolone)
干预措施: Belatacept (Biological)
Basiliximab induction/Short-term Tac
Short term = 3 months
Group 3 Study Therapy Regimen: Induction with 2 doses of basiliximab and tacrolimus for 84 days and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF).
Simulect® (basiliximab); Nulojix® (belatacept); short-term course of Prograf® (tacrolimus), or equivalent; CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL® (methylprednisolone)
干预措施: methylprednisolone (Drug)
结局指标
主要结局
Mean Glomerular Filtration Rate (GFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52
时间窗: Week 52
GFR 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 endstage kidney failure.
次要结局
- Count of Participants With Biopsy Proven Acute Rejection at Any Time Post-Transplant(Transplantation through last study visit (up to week 156))
- Count of Participants With Estimated Glomerular Filtration Rate (GFR) < 60 mL/Min/1.73 m^2 by CKD EPI(Week 52, Week 104, and Week 156)
- Count of Participants by Chronic Kidney Disease (CKD) Stage Post-Transplant(Week 52, Week 104, and Week 156)
- Count of Participants With CKD Stage 4 or 5(Week 52, Week 104, and Week 156)
- Mean Calculated eGFR Using MDRD 4 Variable Model(Week 52, Week 104, and Week 156)
- The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine(Week 52, Week 104, and Week 156)
- Count of Participants With Delayed Graft Function Post-Transplant(Any time within the first week post-transplant)
- An Increase of One or More Grades of CAN/IFTA When Comparing the Implantation and Subsequent Protocol Biopsies(Week 52, Week 104, and Week 156)
- Count of Participants With CAN/IFTA Grade I, II or III at Any Time Post-transplant(Transplantation through last study visit (up to week 156))
- Count of Participants With Acute Cellular Rejection Grade Equal to or Greater Than IA, by the Banff 2007 Criteria(Transplantation through last study visit (up to week 156))
- Count of Participants by Severity of First Acute Cellular Rejection by Wk 52(Transplantation through Week 52)
- Count of Participants With Antibody Mediated Rejection(Transplantation through last study visit (up to week 156))
- Type of Treatment of Rejection(Transplantation through last study visit (up to week 156))
- Count of Participants With de Novo Anti-donor HLA Antibodies at Wk 52(Week 52)
- Count of Participants With Either New Onset Diabetes After Transplant (NODAT) or Impaired Fasting Glucose (IFG) at Wk 52 Based on Criteria Specified by the ADA and WHO(Week 52)
- Count of Participants With Treated Diabetes Between Day 14 and Wk 52(Day 14 to Week 52)
- HbA1c Measured at Days 28 & 84, and Weeks 24, 36, 52, 72, 104 and 156(Day 28, Day 84, Week 24, Week 36, Week 52, Week 72, Week 104, Week 156)
- Standardized Blood Pressure Measurement at Wk 52(Week 52)
- Count of Participants With Use of Anti-hypertensive Medications at Wk 52(Week 52)
- Fasting Lipid Profile (Total Cholesterol, Non-HDL Cholesterol, LDL, HDL, and Triglyceride) at Baseline and Wks 24, 52, 104 and 156(Baseline, Week 24, Week 52, Week 104, Week 156)
- Count of Participants With Use of Lipid Lowering Medications at Baseline and Wks 24, 52, 104 and 156(Baseline, Week 24, Week 52, Week 104, Week 156)
- Total Daily Prescribed Pill Number at Days 28 and 84, and Wks 24, 36, 52, 72, 104 and 156(Day 28, Day 84, Week 24, Week 36, Week 52, Week 72, Week 104, Week 156)
- Number of Events of Death or Graft Loss(Transplantation through last study visit (up to week 156))
- Count of Participants With Rejection(Transplantation through last study visit (up to week 156))
- Number of All Adverse Events (AEs) and Serious Adverse Events (SAEs)(Enrollment through last study visit (up to week 156))
- Count of Participants With Infections Requiring Hospitalization or Systemic Therapy Reported as Serious Adverse Events(Transplantation through last study visit (up to week 156))
- Count of Participants With BKV and CMV Viremia (Local Center Monitoring) Reported as Adverse Events(Transplantation through last study visit (up to week 156))
- Count of Participants With EBV Infection as Reported on the Case Report Form as Adverse Events(Transplantation through last study visit (up to week 156))
- Count of Participants With Fever > 39 Degrees Celsius and Blood Pressure < 90mm Hg Within 24 Hours of Onset of Transplant Procedure(24 hours after transplantation)