NCT01790594终止2 期
Optimization of NULOJIX® (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15)
National Institute of Allergy and Infectious Diseases (NIAID)5 个研究点 分布在 1 个国家目标入组 46 人开始时间: 2013年2月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 46
- 试验地点
- 5
- 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 purpose of this study is to find out if the drug NULOJIX® (belatacept) will minimize the amount of other anti-rejection medications necessary and thereby reduce the long-term side effects caused by the other medications. The researchers also want to learn more about the safety of this treatment and long term health of transplanted pancreases and kidneys.
详细描述
Transplant recipients have to take anti-rejection medications to prevent their immune systems (the body's natural defense system against illness) from rejecting their new organs. Most patients who receive a transplanted organ must take these anti-rejection medications for the rest of their lives, or for as long as the transplanted organ continues to work. Taking standard anti-rejection medications for a long time can cause serious side effects, including pancreas and kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but could lessen the amount of anti-rejection medications that are taken long term.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and provide written informed consent;
- •Candidate for a primary simultaneous kidney and pancreas allograft with random c-peptide <0.3 ng/mL;
- •No known contraindications to study therapy using NULOJIX® (belatacept);
- •Female subjects 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 study completion;
- •No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
- •Negative crossmatch, actual or virtual, or a Panel Reactive Antibodies (PRA) of 0% on historic and admission sera, as determined by each participating study center;
- •A documented negative Tuberculosis (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 transplantation other than a kidney and pancreas;
- •Recipient of previous organ transplant;
- •Epstein-Barr Virus (EBV) sero-negative recipients or recipients whose EBV serostatus is unknown prior to the time of transplantation;
- •Individuals infected by the hepatitis B or C viruses or HIV;
- •Individuals who have required treatment with systemic prednisone or other immunosuppressive drugs within 1 year prior to transplant;
- •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
Immunosuppression without Belatacept
Active Comparator
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: methylprednisolone (Drug)
Immunosuppression without Belatacept
Active Comparator
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: Anti-thymocyte Globulin (Rabbit) (Biological)
Immunosuppression without Belatacept
Active Comparator
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: Tacrolimus (Drug)
Immunosuppression without Belatacept
Active Comparator
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: Mycophenolate mofetil (Drug)
Immunosuppression Including Belatacept
Experimental
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Belatacept
- Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: Belatacept (Biological)
Immunosuppression Including Belatacept
Experimental
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Belatacept
- Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: methylprednisolone (Drug)
Immunosuppression Including Belatacept
Experimental
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Belatacept
- Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: Anti-thymocyte Globulin (Rabbit) (Biological)
Immunosuppression Including Belatacept
Experimental
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Belatacept
- Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: Tacrolimus (Drug)
Immunosuppression Including Belatacept
Experimental
- Induction: 5 day course of methylprednisolone or equivalent;
- Induction: Anti-thymocyte Globulin (Rabbit);
- Maintenance Immunosuppression: Belatacept
- Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below.
- Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).
干预措施: Mycophenolate mofetil (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 Post-Transplant
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 Successful Discontinuation of Tacrolimus in Recipients Randomized to the Investigational Arm(Week 40 through week 48 Post-Transplant)
- Standardized Blood Pressure Measurement From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant(Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 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 Full Pancreatic Graft Function (Insulin Independent) at Wk 52 Post-Transplant(Week 52 Post-Transplant)
- Count of Participants With Evidence of Pancreatic Loss at Week 52 Post-Transplant(Week 52 Post-Transplant)
- Count of Participants by CKD Stage at Wk 52 Post-Transplant(Week 52 Post-Transplant)
- Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant(Transplant through Week 52 Post-Transplant)
- Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant(Week 52 Post-Transplant)
- Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant(Week 52 Post-Transplant)
- Count of Participants With Use of Anti-hypertensive Medication From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant(Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52)
- Count of Participants With De Novo Anti-Donor Antibodies or Anti-Human Leukocyte Antigen (HLA) Antibodies During the First 52 Weeks Post-Transplant(Transplant through Week 52)
- Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant(Week 52 Post-Transplant)
- Count of Participants With Evidence of Partial Pancreatic Graft Function at Week 52 Post-Transplant(Week 52 Post-Transplant)
- Fasting Lipid Profile at Wk 28 Post-Transplant(Week 28 Post-Transplant)
- Lipid Profile at Wk 52 Post-Transplant(Week 52 Post-Transplant)
- Count of Participants With Acute Rejection (AR) of Kidney or Pancreatic Transplant During the First 52 Wks Post-Transplant(Transplant through Week 52)
- HbA1c at Baseline (Pre-Transplant) Through Wk 52 Post-Transplant(Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52)
- Fasting Blood Sugar (FBS) From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant(Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52)
- Count of Participants With Biopsy-Proven Humoral Rejection During the First 52 Weeks Post-Transplant(Transplant through Week 52)
- Fasting Lipid Profile at Baseline (Pre-Transplant)(Baseline (Pre-Transplant))
- Count of Participants With Use of Lipid Lowering Medications at Baseline, Wk 28 and Wk 52 Post-Transplant(Baseline (Pre-Transplant), Week 28, and Week 52)
- Count of Participants Diagnosed With Epstein-Barr Virus (EBV) Infection as an Adverse Event(Transplant through Week 52 Post-Transplant)
- Severity Grade of First Biopsy-Proven Acute Rejection (AR) During the First 52 Weeks Post-Transplant(Transplant through Week 52)
- Count of Participants With an Infectious Disease Serious Adverse Event(s) Requiring Hospitalization or Systemic Therapy(Transplant through Week 52 Post-Transplant)
- Count of Participants Diagnosed With Malignancy as an Adverse Event(Transplant through Week 52 Post-Transplant)
- Type of Treatment(s) Participants Received for Biopsy-Proven Renal Allograft Rejection During the First 52 Weeks Post-Transplant(Transplant through Week 52)
- Type of Treatment(s) Participants Received for Biopsy-Proven Pancreatic Allograft Rejection During the First 52 Weeks Post-Transplant(Transplant through Week 52)
- Count of Participants With Event of Death, Graft Loss, or Undetectable C-peptide(Transplant through Week 52 Post-Transplant)
- Count of Participants With the Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Enrollment (Pre-Transplant) to Week 52 Post-Transplant)
- Count of Participant Diagnosed With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia As Adverse Events(Transplant through Week 52 Post-Transplant)
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研究点 (5)
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