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Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01790594
Recruitment Status : Terminated (Slow accrual within enrollment time period: projected accrual goal not achieved.)
First Posted : February 13, 2013
Results First Posted : December 7, 2017
Last Update Posted : July 20, 2021
Sponsor:
Collaborators:
Clinical Trials in Organ Transplantation
Rho Federal Systems Division, Inc.
Bristol-Myers Squibb
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE February 11, 2013
First Posted Date  ICMJE February 13, 2013
Results First Submitted Date  ICMJE October 6, 2017
Results First Posted Date  ICMJE December 7, 2017
Last Update Posted Date July 20, 2021
Study Start Date  ICMJE February 2013
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2017)
Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
Mean glomerular filtration rate (GFR) [ Time Frame: 52 weeks ]
calculated for each treatment group using the Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2017)
  • Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant [ Time Frame: 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.
  • Count of Participants by CKD Stage at Wk 52 Post-Transplant [ Time Frame: Week 52 Post-Transplant ]
    The stages of Chronic Kidney Disease are defined using the participant's GFR value:
    • Stage 1 if GFR value is ≥90 ( kidney function is normal)
    • Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease)
    • Stage 3A if 45 ≤ GFR < 60*
    • Stage 3B if 30 ≤ GFR < 45*
    • Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function)
    • Stage 5 if GFR < 15 (severe or end stage kidney failure).
    Stages 3A and 3B indicate moderately reduced kidney function.*
  • Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant [ Time Frame: Week 52 Post-Transplant ]
    The stages of Chronic Kidney Disease (CKD) are defined using the participant's GFR value:
    • Stage 1 if GFR value is ≥ 90 (kidney function is normal)
    • Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease)
    • Stage 3A if 45 <= GFR < 60*
    • Stage 3B if 30 <= GFR < 45*
    • Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function)
    • Stage 5 if GFR < 15 (severe or end stage kidney failure).
    Stages 3A abd 3B indicate moderately reduced kidney function.*
  • Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant [ Time Frame: Week 52 Post-Transplant ]
    The estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation (MDRD):
    • 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 severe or endstage kidney failure.
  • The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant [ Time Frame: Day 28 through Week 52 Post-Transplant ]
    The estimated Glomerular Filtration Rate (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 endstage kidney failure.
    An estimate of the slope, or change over time, in eGFR was produced using standard statistical linear modeling procedures. The estimate was then re-scaled so that it could be interpreted as a change in eGFR per month. Positive numbers indicate increasing kidney function. Larger numbers indicate greater change in kidney function.
  • Count of Participants With Successful Discontinuation of Tacrolimus in Recipients Randomized to the Investigational Arm [ Time Frame: Week 40 through week 48 Post-Transplant ]
    Participants achieved successful discontinuation if they were able to discontinue (e.g., off tacrolimus therapy completely) over a 4-8 weeks after tacrolimus withdrawal was initiated at week 40.
  • Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant [ Time Frame: Transplant through Week 52 Post-Transplant ]
    Delayed grafted function is defined as dialysis in the first week on one or more occasions for any indication other than the treatment of acute hyperkalemia in the setting of otherwise acceptable renal function.
  • Count of Participants With Full Pancreatic Graft Function (Insulin Independent) at Wk 52 Post-Transplant [ Time Frame: Week 52 Post-Transplant ]
    Participants with full pancreatic graft functions are defined as those that no longer require exogenous insulin therapy.
  • Count of Participants With Evidence of Partial Pancreatic Graft Function at Week 52 Post-Transplant [ Time Frame: Week 52 Post-Transplant ]
    C-peptide is a measure of pancreatic function. The definition of partial pancreatic graft function: a fasting C-peptide levels >0.3ng.mL (0.1nmol.L) plus the participant's continued requirement for exogenous insulin or oral hypoglycemic agent(s).
  • Count of Participants With Evidence of Pancreatic Loss at Week 52 Post-Transplant [ Time Frame: Week 52 Post-Transplant ]
    C-peptide is a measure of pancreatic function. The definition of pancreatic loss: a C-peptide value of <0.3 ng/mL.
  • HbA1c at Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [ Time Frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52 ]
    Hemoglobin A1c (HbA1c) measures the average blood glucose levels over 8-12 weeks, thus acting as a useful long-term gauge of blood glucose control:
    • A value below 6.0% reflects normal levels,
    • 6.0% to 6.4% reflects prediabetes, and
    • a value of ≥ 6.5% reflects diabetes.
  • Fasting Blood Sugar (FBS) From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [ Time Frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52 ]
    Fasting blood sugar (e.g., glucose) test is used to help diagnose diabetes, prediabetes, and gestational diabetes. Reference fasting blood sugar (glucose) values:
    • 70 to 99 mg/dL is normal
    • 100 to 125 mg/dL is considered prediabetes
    • 126 mg/dL or higher on two separate tests is considered diabetes.
  • Standardized Blood Pressure Measurement From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [ Time Frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52 ]
    A blood pressure measurement consists of two numbers: the systolic and diastolic pressures. Systolic pressure measures the pressure in blood vessels when the heart beats. Diastolic pressure measures the pressure in blood vessels between beats of the heart.
    • Systolic measures of <120 and diastolic measures of <80 are considered normal.
    • Systolic measures of 120-139 and diastolic measures of 80-89 are considered at risk (or pre-hypertension).
    • Systolic measures of ≥140 and diastolic measures of ≥90 are considered high.
  • Count of Participants With Use of Anti-hypertensive Medication From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [ Time Frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52 ]
    Anti-hypertensive medications are a class of drugs that are used to treat hypertension. The medications seek to prevent the complications of high blood pressure, such as stoke and myocardial infarction.
  • Fasting Lipid Profile at Baseline (Pre-Transplant) [ Time Frame: Baseline (Pre-Transplant) ]
    A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided:
    • Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease
    • LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease
    • HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease
    • Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and
    • Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
  • Fasting Lipid Profile at Wk 28 Post-Transplant [ Time Frame: Week 28 Post-Transplant ]
    A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided:
    • Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease
    • LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease
    • HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease
    • Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and
    • Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
  • Lipid Profile at Wk 52 Post-Transplant [ Time Frame: Week 52 Post-Transplant ]
    A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided:
    • Total cholesterol: 75-169 mg/dL if age ≤ 20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease
    • LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease
    • HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease
    • Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and
    • Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
  • Count of Participants With Use of Lipid Lowering Medications at Baseline, Wk 28 and Wk 52 Post-Transplant [ Time Frame: Baseline (Pre-Transplant), Week 28, and Week 52 ]
    Lipid lowering medications are used in the treatment of high levels of fats (lipids), such as cholesterol in blood
  • Count of Participants With Acute Rejection (AR) of Kidney or Pancreatic Transplant During the First 52 Wks Post-Transplant [ Time Frame: Transplant through Week 52 ]
    Biopsy-proven acute rejection (AR) of the kidney (renal) or pancreas during the first 52 weeks post-transplant. AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1.
    • AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe.
    • AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded as I, II, or III, with I defined as the mildest form of AR and III being the most severe.
  • Severity Grade of First Biopsy-Proven Acute Rejection (AR) During the First 52 Weeks Post-Transplant [ Time Frame: Transplant through Week 52 ]
    AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1.
    • AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe.
    • AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded is I, II, or III, with I defined as the mildest form of AR and III being the most severe.
  • Count of Participants With Biopsy-Proven Humoral Rejection During the First 52 Weeks Post-Transplant [ Time Frame: Transplant through Week 52 ]
    Humoral rejection (i.e., antibody mediated rejection) of:
    1. the kidney as defined by diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury determined by local pathology and,
    2. the pancreas as defined by the presence of circulating anti-donor antibodies, and histopathological data including morphologic evidence of microvascular tissue injury and C4d staining in interacinar capillaries determined by local pathology.
  • Count of Participants With De Novo Anti-Donor Antibodies or Anti-Human Leukocyte Antigen (HLA) Antibodies During the First 52 Weeks Post-Transplant [ Time Frame: Transplant through Week 52 ]
    The de novo development of donor-specific antibody (DSA) is associated with an increased risk of graft rejection. The presence of anti-Histocompatibility Antigen (HLA) antibodies (alloantibodies) is associated with increased risk of acute and chronic injury to the transplant allograft.
  • Type of Treatment(s) Participants Received for Biopsy-Proven Renal Allograft Rejection During the First 52 Weeks Post-Transplant [ Time Frame: Transplant through Week 52 ]
    Participants are stratified by kidney biopsy results/treatment received. In the event of a for cause renal (kidney) biopsy: -The diagnosis of acute cellular rejection (ACR) using the Banff 2007 renal allograft pathology criteria. These criteria for renal allograft biopsies is an international histopathological classification standard. ACR is defined by a renal biopsy demonstrating a Banff 2007 classification of Grade IA or greater, with higher scores indicating more severe rejection. (Ref: Solez K, Colvin RB et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008 8(4): 753-60). Acronyms and abbreviations:
    • ACR=Acute Cellular Rejection*
    • Normal*
    • Borderline* (criteria for ACR not fulfilled)
    • Gd.=Grade*
    • IFTA=Interstitial Fibrosis and Tubular Atrophy*
    • ATG=Anti-thymocyte globulin therapy
    • IVIG=Intravenous Immunoglobulin therapy
    • PO=Orally
    • QD=Daily *Banff 2007 renal allograft pathology criteria
  • Type of Treatment(s) Participants Received for Biopsy-Proven Pancreatic Allograft Rejection During the First 52 Weeks Post-Transplant [ Time Frame: Transplant through Week 52 ]
    Participants are stratified by kidney biopsy results/treatment received. Upon having a for-cause biopsy performed, persons often receive treatment for rejection based on the biopsy results, which may or may not reveal signs of rejection. Details of biopsy findings and corresponding treatment are provided for each instance of treatment for rejection. Results summary format: biopsy results; treatment. Acronyms and abbreviations:
    • ACR=Acute Cellular Rejection
    • IFTA=Interstitial Fibrosis and Tubular Atrophy
    • ATG=Anti-thymocyte globulin therapy
    • IVIG=Intravenous Immunoglobulin therapy
    • Gd =Grade
    • PO=Orally
    • QD=Daily
  • Count of Participants With Event of Death, Graft Loss, or Undetectable C-peptide [ Time Frame: Transplant through Week 52 Post-Transplant ]
    This measure counts death, graft loss, or undetectable C-peptide value (e.g., C-peptide <0.3 ng/mL) occurring at any point post-transplant and independent of each other.
    • Kidney Graft Loss was defined as 90 consecutive days of dialysis dependency.
    • Pancreas graft loss was defined as returning to exogenous insulin therapy or initiation of oral hypoglycemic agents for greater than 30 days.
    • Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum insulin levels and low or undetectable C-peptide levels.
  • Count of Participants With the Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Enrollment (Pre-Transplant) to Week 52 Post-Transplant ]
    Adverse events were collected systematically. Counts of all participants who experienced at least one adverse event (AEs, SAEs) by assigned treatment group. Refer to the Serious Adverse Events and Other Adverse Events tables for more detail.
  • Count of Participants With an Infectious Disease Serious Adverse Event(s) Requiring Hospitalization or Systemic Therapy [ Time Frame: Transplant through Week 52 Post-Transplant ]
    Infections were required to be reported as a serious adverse event if they required either inpatient hospitalization or prolongation of a current hospitalization. Displayed are counts of all participants who experienced infection(s) as an adverse event, by treatment group.
  • Count of Participant Diagnosed With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia As Adverse Events [ Time Frame: Transplant through Week 52 Post-Transplant ]
    Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of participants who experienced BKV and CMV viremia as adverse events, diagnosed by test results from the local clinical pathology laboratory.
  • Count of Participants Diagnosed With Epstein-Barr Virus (EBV) Infection as an Adverse Event [ Time Frame: Transplant through Week 52 Post-Transplant ]
    Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of all participants diagnosed with EBV infection as an adverse event by EBV test(s), diagnosed by test results from the local clinical pathology laboratory.
  • Count of Participants Diagnosed With Malignancy as an Adverse Event [ Time Frame: Transplant through Week 52 Post-Transplant ]
    An increased risk/incidence of malignancy is a recognized complication of immunosuppression in recipients of organ transplants. In Phase 3 clinical trials, overall malignancy rates were similar across all treatment groups, with the exception of posttransplant lymphoproliferative disease (PTLD).Displayed are counts of all participants who experienced malignancy reported as an adverse event.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
  • Measures of Renal Function and Injury [ Time Frame: 52, 104, 156 weeks ]
    • Proportion of subjects with eGFR < 60 mL/min/1.73 m2 measured by CKD-EPI
    • Change in CKD stages from baseline
    • Proportion of subjects with defined CKD stage 4 or 5
    • Mean calculated eGFR using MDRD 4 variable model
    • eGFR by CKD-EPI over time based on serum creatinine
    • Incidence of successful discontinuation of tacrolimus in recipients randomized to the investigational arm
    • Incidence of delayed graft function
    • An increase of one or more grades of CAN/IFTA when comparing the implantation and subsequent protocol biopsies
    • Incidence of CAN/IFTA grade 1, 2, 3
  • Measures of Cardiovascular and Metabolic Parameters [ Time Frame: baseline, days 28, 84, and weeks 28, 36, 52, 72, 104 and 156 ]
    • HbA1c fasting Blood Sugar (FBS)
    • standardized blood pressure measurement and use of anti-hypertensive medications
    • fasting lipid profile
    • the use of lipid lowering medications
  • Incidence and Severity of Rejection and Anti-Donor Reactivity [ Time Frame: 52 weeks, post-transplant ]
    • Incidence and severity of acute cellular rejection (also measured at weeks 104 and 156)
    • Severity of first and highest grade of acute cellular rejection in the renal and pancreas biopsies
    • Incidence of humoral rejection in the renal and pancreas biopsies
    • Prevalence of de novo anti-donor antibodies and anti-HLA antibodies
    • Type of treatment of rejection.
  • Safety Outcome Measures [ Time Frame: 52, 104, 156 weeks ]
    • Incidence of death
    • Graft loss
    • Undetectable c-peptide
    • All adverse events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation
Official Title  ICMJE Optimization of NULOJIX® (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15)
Brief Summary 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Simultaneous Kidney and Pancreas Transplantation
Intervention  ICMJE
  • Biological: Belatacept
    The first dose of belatacept will be administered approximately 24-48 hours after the last dose of Anti-Thymocyte Globulin (Rabbit).
    Other Name: NULOJIX
  • Drug: methylprednisolone
    Other Name: Medrol
  • Biological: Anti-thymocyte Globulin (Rabbit)
    Other Names:
    • Thymoglobulin
    • ATG (Rabbit)
  • Drug: Tacrolimus
    There may be an opportunity to withdraw tacrolimus at week 40
    Other Name: Prograf
  • Drug: Mycophenolate mofetil
    Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.
    Other Name: MMF, mycophenolate sodium, CellCept
Study Arms  ICMJE
  • Active Comparator: Immunosuppression without Belatacept
    • 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).
    Interventions:
    • Drug: methylprednisolone
    • Biological: Anti-thymocyte Globulin (Rabbit)
    • Drug: Tacrolimus
    • Drug: Mycophenolate mofetil
  • Experimental: Immunosuppression Including Belatacept
    • 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).
    Interventions:
    • Biological: Belatacept
    • Drug: methylprednisolone
    • Biological: Anti-thymocyte Globulin (Rabbit)
    • Drug: Tacrolimus
    • Drug: Mycophenolate mofetil
Publications * Stock PG, Mannon RB, Armstrong B, Watson N, Ikle D, Robien MA, Morrison Y, Odorico J, Fridell J, Mehta AK, Newell KA. Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial. Am J Transplant. 2020 Jun;20(6):1668-1678. doi: 10.1111/ajt.15817. Epub 2020 Mar 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 15, 2015)
46
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2013)
60
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01790594
Other Study ID Numbers  ICMJE DAIT CTOT-15
U01AI084150 ( U.S. NIH Grant/Contract )
NIAID CRMS ID#: 20117 ( Other Identifier: DAIT NIAID )
SDY1433 ( Other Identifier: ImmPort )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data is available in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Supporting Materials: Study Protocol
Time Frame: On average, data is available within 24 months after database lock for a trial.
Access Criteria:

Open access.

Study's:

  • Accession ID is SDY1433, and
  • Digital Object Identifier (DOI) is : 10.21430/M3CEH2A7ZF
URL: https://www.immport.org/home
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Same as current
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Clinical Trials in Organ Transplantation
  • Rho Federal Systems Division, Inc.
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Kenneth Newell, MD, PhD Emory University
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP